Psoriasis

Apremilast is a small-molecule biologic approved by the US Food and Drug Administration (FDA) for use in plaque psoriasis, psoriatic arthritis, and Behçet disease.^1-6 Although apremilast is seemingly a less favorable choice for treating psoriasis in the era of injectable biologics, the drug is an important option for patients in the military. In recent months, apremilast also emerged as one of a few systemic medications recommended for the treatment of psoriasis and other dermatologic conditions during the COVID-19 pandemic.⁷

In this article, we review on-label indications and off-label uses for apremilast; highlight the importance of apremilast for managing psoriasis in the military population; and propose other patient populations in whom the use of apremilast is favorable. We also present a case report that highlights and embodies the benefit of apremilast for military service members.

CASE REPORT

A 28-year-old active-duty male US Navy service member developed extensive guttate psoriasis in a distribution too wide to manage with topical medication (Figure, A–C). His condition did not improve with a trial of oral antibiotics, and he reported itch that affected his sleep. He denied new joint pain, swelling, or deformity.

A review of the patient’s service history revealed that he was serving aboard a guided-missile cruiser ship for a tour extending an additional 2 years. Limited medical resources and lack of refrigeration made the use of injectable biologics, such as adalimumab, infeasible. Furthermore, the patient was too critical to the mission to be transported frequently off the ship to a higher level of care for injection of medication. He also had trouble returning for appointments and refills because of the high operational tempo of his command.

After discussion with the patient, oral apremilast was started at 30 mg/d and titrated up to the standard dosing of 30 mg twice daily, with excellent results by 3 months after he started therapy (Figure, D–F).

COMMENT

We reviewed the research on apremilast for its approved indications, including psoriasis; its off-label uses; and strategies for using the drug to treat psoriasis and other dermatologic conditions in military populations. The most recent evidence regarding the use of apremilast in dermatology, rheumatology, and other medical specialties was assessed using published English-language research data and review articles. We conducted a PubMed search of articles indexed for MEDLINE using the following terms: apremilast, Otezla, psoriasis, psoriatic arthritis, arthritis, off-label, Behçet’s, hidradenitis suppurativa, military, and armed forces. We also reviewed citations within relevant articles to identify additional relevant sources.

Off-label uses reviewed here are based on data from randomized controlled trials, large open-label trials, and large prospective case series. Articles with less evidence are not included in this review.

On-Label Usage Profile

Apremilast is an orally administered, small-molecule inhibitor of phosphodiesterase 4. Small-molecule inhibitors are a class of medications with low molecular weight, high stability, and short half-life. They act intracellularly to modulate proinflammatory states through regulation of the proinflammatory cytokine milieu.

Apremilast has been approved by the FDA for use in adult psoriasis and psoriatic arthritis since 2014 and for use in treating oral ulcers of Behçet disease since 2019.^1-3,5,6 Recently, a phase 2, multicenter, open-label study on the use of apremilast in pediatric psoriasis patients (aged 12–17 years) demonstrated a similar safety profile with weight-based dosing⁸; phase 3 trials in this population are in the recruitment phase (ClinicalTrials.gov Identifier NCT03701763).

Because information regarding its use in pregnancy is limited, apremilast is not recommended in this population. It is unknown whether apremilast is present in breast milk; although the manufacturer does not make explicit recommendations regarding use during breastfeeding, an expert panel reviewing management of psoriasis in pregnant and breastfeeding women recommended avoiding its use while breastfeeding.⁹

Common Adverse Effects

Common adverse effects (AEs) include weight loss (>5% total body weight in 5% of patients; 5%–10% of total body weight in 10%–12% of patients; and ≥10% total body weight in 2% of patients), diarrhea and nausea, headache, and upper respiratory tract infection.^10,11 Gastrointestinal AEs tend to be self-limited and improve or resolve after the first few weeks of therapy. Caution is advised in patients older than 65 years and in those at risk for hypotension or volume depletion. Although depressed mood is a rare AE (<1%), apremilast should be used cautiously in patients with a history of depression or suicidal ideation. Weight loss generally is self-limited; routine monitoring of weight is recommended.¹¹

Apremilast in Psoriasis and Psoriatic Arthritis

Psoriasis
The ESTEEM trials established the safety and efficacy of apremilast for use in psoriasis.^2,3 In a phase 3, multicenter, double-blind, placebo-controlled trial of 844 patients, apremilast demonstrated a statistically significant 75% or greater reduction from the baseline psoriasis area and severity index score (PASI-75) in 33.1% of patients receiving the medication compared to 5.3% of those receiving placebo.² Data from real-world practice (outside constraints of clinical trials) suggest slightly greater efficacy than was demonstrated in the ESTEEM trials.

A recently published retrospective, cross-sectional study of 480 patients with psoriasis treated with apremilast reported that 48.6% of patients continuing therapy for a mean (SD) of 6 (1) months achieved PASI-75. Furthermore, the mean dermatology life quality index (DLQI) score of the surveyed population decreased from 13.4 at initiation of treatment to 5.7 at 6 (1) months of treatment—a marked improvement in quality of life.¹² Other single-center and smaller study populations also have suggested increased real-world benefit.^13,14

Nonetheless, the rate and degree of clearance of plaques with apremilast seem to lag behind what is observed with many of the biologics and traditional medications employed to treat psoriasis.^15-19 Furthermore, indirect cost analysis comparisons suggest a much higher cost per level of PASI for apremilast compared to several biologics and to methotrexate.^20,21 A study that used indirect methods of comparison to analyze the comparative cost and efficacy of apremilast and methotrexate found no evidence of greater efficacy for apremilast and that the incremental cost to achieve 1 additional PASI-75 responder by using apremilast is $187,888 annually.²¹

Psoriatic Arthritis
The PALACE clinical trials 1, 2, and 3 assessed the efficacy of apremilast in patients who had prior treatment with conventional disease-modifying antirheumatic drugs or biologics, or both. PALACE 4 evaluated efficacy in treatment-naïve patients; standard dosing of apremilast was found to produce improvement in psoriatic arthritis in treatment-naïve and non–treatment-naïve patients.^4-6,22 In the 24-week placebo-controlled phase of the PALACE 1 trial, the American College of Rheumatology (ACR) baseline composite measurement of 20% disease improvement, or ACR20, was achieved in 40% of patients randomized to the standard dosing regimen compared to 19% of patients receiving placebo, a statistically significant result (P<.001).²²

Evaluation of long-term study data is beyond the scope of this review, but those data suggest that disease outcomes continue to improve the longer therapy is utilized, with a greater percentage of patients achieving ACR20 as well as ACR50 (50% improvement) and ACR70 (70% improvement) responses. Indirect comparisons analyzing the cost and effectiveness for adalimumab, apremilast, and methotrexate in patients with psoriatic arthritis found that apremilast was less effective than adalimumab and as efficacious as methotrexate, though apremilast carries the highest price tag of these drugs.²³

Off-Label Uses

Ease of oral administration and a favorable safety profile have prompted off-label study of apremilast in other inflammatory skin diseases, including atopic dermatitis, hidradenitis suppurativa, lichen planus, rosacea, alopecia areata, and cutaneous sarcoidosis. Publications with a minimum case series of 10 patients are included in the Table.^24-32

Use in the Military and Beyond

Psoriasis and other inflammatory skin conditions are common in the military and can greatly hinder a service member’s ability to perform their duties and remain ready to deploy. A history of psoriasis is disqualifying for military recruits, but early entry into service, misdiagnosis, and low or no burden of disease at time of entry into the service all contribute to a substantial population of active-duty service members who require treatment of psoriasis.³³ Necessity dictates that treatment of this condition extend to theater operations; from 2008 to 2015, more than 3600 soldiers sought care for psoriasis while deployed to a combat theater.³⁴

In some cases, poorly controlled inflammatory skin conditions lead to medical separation.³³ Although there are limited data on the use of apremilast in the military, its use during deployment for the treatment of psoriasis and psoriatic arthritis has been reported, with the great majority of service members retaining their deployable status even 1 year after the study period.³⁵

The ideal medication for deployable military personnel should have low toxicity, simple storage, and minimal monitoring requirements, and it should not expose a service member to increased risk while in a combat theater. Worldwide deployability is a requirement for most military occupations. The risk for immunosuppression with targeted immune therapy must be fully weighed, as certain duty stations and deployments might increase the risk for exposure to Mycobacterium tuberculosis, endemic mycopathogens, hepatitis C virus, HIV, Leishmania, and Strongyloides.³⁴

Furthermore, the tumor necrosis factor α inhibitors and IL-17 and IL-23 blockers used to treat psoriasis all require refrigeration; often, this requirement cannot be met in austere overseas settings. Additional requirements for laboratory monitoring, titration of medications, and frequent office visits might prohibit a service member from performing their duties, which, in turn, is detrimental to military readiness and the career of that service member.

Last, the Centers for Disease Control and Prevention recommend avoiding live virus vaccination while taking targeted immune therapy because of safety and effectiveness concerns during immunosuppression.³⁶ This recommendation might disqualify military personnel from deployment to certain locations that require the protection that such vaccines afford. Therefore, apremilast is an ideal option for the military patient population, with many military-specific advantages.

Of course, the military is not the only population in whom ease of use and storage and simplified monitoring parameters are essential. Benefits of apremilast also may translate to patients who are placed in austere conditions or who participate in extended worldwide travel for work or leisure, such as government contractors who deploy in support of military operations, firefighters or national park employees who spend extended periods in resource-limited settings, and foreign-aid workers and diplomats who are engaged in frequent travel around the world. Furthermore, travel to certain regions might increase the risk for exposure to atypical pathogens as well as the desire for a therapeutic option that does not have potential to suppress the immune system. This subset of psoriasis patients might be better treated with novel agents such as apremilast than other drugs that would be the presumed standard of care in a domestic setting.

Final Thoughts

The benefits of apremilast translate to all patients in austere environments with limited resources and during times when immune function is of utmost concern. For military service members and many civilians in austere environments worldwide, apremilast could be considered a first-line systemic agent for psoriasis and psoriatic arthritis. In patients unable to use or tolerate other treatments, apremilast can be considered for off-label therapy (Table^24-32). There are times when the approach to prescribing must look beyond primary efficacy, AE profile, and cost—to include occupation, environment, or duties—to select the optimal medication for a patient.

Apremilast is a small-molecule biologic approved by the US Food and Drug Administration (FDA) for use in plaque psoriasis, psoriatic arthritis, and Behçet disease.^1-6 Although apremilast is seemingly a less favorable choice for treating psoriasis in the era of injectable biologics, the drug is an important option for patients in the military. In recent months, apremilast also emerged as one of a few systemic medications recommended for the treatment of psoriasis and other dermatologic conditions during the COVID-19 pandemic.⁷

In this article, we review on-label indications and off-label uses for apremilast; highlight the importance of apremilast for managing psoriasis in the military population; and propose other patient populations in whom the use of apremilast is favorable. We also present a case report that highlights and embodies the benefit of apremilast for military service members.

CASE REPORT

A 28-year-old active-duty male US Navy service member developed extensive guttate psoriasis in a distribution too wide to manage with topical medication (Figure, A–C). His condition did not improve with a trial of oral antibiotics, and he reported itch that affected his sleep. He denied new joint pain, swelling, or deformity.

A review of the patient’s service history revealed that he was serving aboard a guided-missile cruiser ship for a tour extending an additional 2 years. Limited medical resources and lack of refrigeration made the use of injectable biologics, such as adalimumab, infeasible. Furthermore, the patient was too critical to the mission to be transported frequently off the ship to a higher level of care for injection of medication. He also had trouble returning for appointments and refills because of the high operational tempo of his command.

After discussion with the patient, oral apremilast was started at 30 mg/d and titrated up to the standard dosing of 30 mg twice daily, with excellent results by 3 months after he started therapy (Figure, D–F).

COMMENT

We reviewed the research on apremilast for its approved indications, including psoriasis; its off-label uses; and strategies for using the drug to treat psoriasis and other dermatologic conditions in military populations. The most recent evidence regarding the use of apremilast in dermatology, rheumatology, and other medical specialties was assessed using published English-language research data and review articles. We conducted a PubMed search of articles indexed for MEDLINE using the following terms: apremilast, Otezla, psoriasis, psoriatic arthritis, arthritis, off-label, Behçet’s, hidradenitis suppurativa, military, and armed forces. We also reviewed citations within relevant articles to identify additional relevant sources.

Off-label uses reviewed here are based on data from randomized controlled trials, large open-label trials, and large prospective case series. Articles with less evidence are not included in this review.

On-Label Usage Profile

Apremilast is an orally administered, small-molecule inhibitor of phosphodiesterase 4. Small-molecule inhibitors are a class of medications with low molecular weight, high stability, and short half-life. They act intracellularly to modulate proinflammatory states through regulation of the proinflammatory cytokine milieu.

Apremilast has been approved by the FDA for use in adult psoriasis and psoriatic arthritis since 2014 and for use in treating oral ulcers of Behçet disease since 2019.^1-3,5,6 Recently, a phase 2, multicenter, open-label study on the use of apremilast in pediatric psoriasis patients (aged 12–17 years) demonstrated a similar safety profile with weight-based dosing⁸; phase 3 trials in this population are in the recruitment phase (ClinicalTrials.gov Identifier NCT03701763).

Because information regarding its use in pregnancy is limited, apremilast is not recommended in this population. It is unknown whether apremilast is present in breast milk; although the manufacturer does not make explicit recommendations regarding use during breastfeeding, an expert panel reviewing management of psoriasis in pregnant and breastfeeding women recommended avoiding its use while breastfeeding.⁹

Common Adverse Effects

Common adverse effects (AEs) include weight loss (>5% total body weight in 5% of patients; 5%–10% of total body weight in 10%–12% of patients; and ≥10% total body weight in 2% of patients), diarrhea and nausea, headache, and upper respiratory tract infection.^10,11 Gastrointestinal AEs tend to be self-limited and improve or resolve after the first few weeks of therapy. Caution is advised in patients older than 65 years and in those at risk for hypotension or volume depletion. Although depressed mood is a rare AE (<1%), apremilast should be used cautiously in patients with a history of depression or suicidal ideation. Weight loss generally is self-limited; routine monitoring of weight is recommended.¹¹

Apremilast in Psoriasis and Psoriatic Arthritis

Psoriasis
The ESTEEM trials established the safety and efficacy of apremilast for use in psoriasis.^2,3 In a phase 3, multicenter, double-blind, placebo-controlled trial of 844 patients, apremilast demonstrated a statistically significant 75% or greater reduction from the baseline psoriasis area and severity index score (PASI-75) in 33.1% of patients receiving the medication compared to 5.3% of those receiving placebo.² Data from real-world practice (outside constraints of clinical trials) suggest slightly greater efficacy than was demonstrated in the ESTEEM trials.

A recently published retrospective, cross-sectional study of 480 patients with psoriasis treated with apremilast reported that 48.6% of patients continuing therapy for a mean (SD) of 6 (1) months achieved PASI-75. Furthermore, the mean dermatology life quality index (DLQI) score of the surveyed population decreased from 13.4 at initiation of treatment to 5.7 at 6 (1) months of treatment—a marked improvement in quality of life.¹² Other single-center and smaller study populations also have suggested increased real-world benefit.^13,14

Nonetheless, the rate and degree of clearance of plaques with apremilast seem to lag behind what is observed with many of the biologics and traditional medications employed to treat psoriasis.^15-19 Furthermore, indirect cost analysis comparisons suggest a much higher cost per level of PASI for apremilast compared to several biologics and to methotrexate.^20,21 A study that used indirect methods of comparison to analyze the comparative cost and efficacy of apremilast and methotrexate found no evidence of greater efficacy for apremilast and that the incremental cost to achieve 1 additional PASI-75 responder by using apremilast is $187,888 annually.²¹

Psoriatic Arthritis
The PALACE clinical trials 1, 2, and 3 assessed the efficacy of apremilast in patients who had prior treatment with conventional disease-modifying antirheumatic drugs or biologics, or both. PALACE 4 evaluated efficacy in treatment-naïve patients; standard dosing of apremilast was found to produce improvement in psoriatic arthritis in treatment-naïve and non–treatment-naïve patients.^4-6,22 In the 24-week placebo-controlled phase of the PALACE 1 trial, the American College of Rheumatology (ACR) baseline composite measurement of 20% disease improvement, or ACR20, was achieved in 40% of patients randomized to the standard dosing regimen compared to 19% of patients receiving placebo, a statistically significant result (P<.001).²²

Evaluation of long-term study data is beyond the scope of this review, but those data suggest that disease outcomes continue to improve the longer therapy is utilized, with a greater percentage of patients achieving ACR20 as well as ACR50 (50% improvement) and ACR70 (70% improvement) responses. Indirect comparisons analyzing the cost and effectiveness for adalimumab, apremilast, and methotrexate in patients with psoriatic arthritis found that apremilast was less effective than adalimumab and as efficacious as methotrexate, though apremilast carries the highest price tag of these drugs.²³

Off-Label Uses

Ease of oral administration and a favorable safety profile have prompted off-label study of apremilast in other inflammatory skin diseases, including atopic dermatitis, hidradenitis suppurativa, lichen planus, rosacea, alopecia areata, and cutaneous sarcoidosis. Publications with a minimum case series of 10 patients are included in the Table.^24-32

Use in the Military and Beyond

Psoriasis and other inflammatory skin conditions are common in the military and can greatly hinder a service member’s ability to perform their duties and remain ready to deploy. A history of psoriasis is disqualifying for military recruits, but early entry into service, misdiagnosis, and low or no burden of disease at time of entry into the service all contribute to a substantial population of active-duty service members who require treatment of psoriasis.³³ Necessity dictates that treatment of this condition extend to theater operations; from 2008 to 2015, more than 3600 soldiers sought care for psoriasis while deployed to a combat theater.³⁴

In some cases, poorly controlled inflammatory skin conditions lead to medical separation.³³ Although there are limited data on the use of apremilast in the military, its use during deployment for the treatment of psoriasis and psoriatic arthritis has been reported, with the great majority of service members retaining their deployable status even 1 year after the study period.³⁵

The ideal medication for deployable military personnel should have low toxicity, simple storage, and minimal monitoring requirements, and it should not expose a service member to increased risk while in a combat theater. Worldwide deployability is a requirement for most military occupations. The risk for immunosuppression with targeted immune therapy must be fully weighed, as certain duty stations and deployments might increase the risk for exposure to Mycobacterium tuberculosis, endemic mycopathogens, hepatitis C virus, HIV, Leishmania, and Strongyloides.³⁴

Furthermore, the tumor necrosis factor α inhibitors and IL-17 and IL-23 blockers used to treat psoriasis all require refrigeration; often, this requirement cannot be met in austere overseas settings. Additional requirements for laboratory monitoring, titration of medications, and frequent office visits might prohibit a service member from performing their duties, which, in turn, is detrimental to military readiness and the career of that service member.

Last, the Centers for Disease Control and Prevention recommend avoiding live virus vaccination while taking targeted immune therapy because of safety and effectiveness concerns during immunosuppression.³⁶ This recommendation might disqualify military personnel from deployment to certain locations that require the protection that such vaccines afford. Therefore, apremilast is an ideal option for the military patient population, with many military-specific advantages.

Of course, the military is not the only population in whom ease of use and storage and simplified monitoring parameters are essential. Benefits of apremilast also may translate to patients who are placed in austere conditions or who participate in extended worldwide travel for work or leisure, such as government contractors who deploy in support of military operations, firefighters or national park employees who spend extended periods in resource-limited settings, and foreign-aid workers and diplomats who are engaged in frequent travel around the world. Furthermore, travel to certain regions might increase the risk for exposure to atypical pathogens as well as the desire for a therapeutic option that does not have potential to suppress the immune system. This subset of psoriasis patients might be better treated with novel agents such as apremilast than other drugs that would be the presumed standard of care in a domestic setting.

Final Thoughts

The benefits of apremilast translate to all patients in austere environments with limited resources and during times when immune function is of utmost concern. For military service members and many civilians in austere environments worldwide, apremilast could be considered a first-line systemic agent for psoriasis and psoriatic arthritis. In patients unable to use or tolerate other treatments, apremilast can be considered for off-label therapy (Table^24-32). There are times when the approach to prescribing must look beyond primary efficacy, AE profile, and cost—to include occupation, environment, or duties—to select the optimal medication for a patient.

Apremilast is a small-molecule biologic approved by the US Food and Drug Administration (FDA) for use in plaque psoriasis, psoriatic arthritis, and Behçet disease.^1-6 Although apremilast is seemingly a less favorable choice for treating psoriasis in the era of injectable biologics, the drug is an important option for patients in the military. In recent months, apremilast also emerged as one of a few systemic medications recommended for the treatment of psoriasis and other dermatologic conditions during the COVID-19 pandemic.⁷

In this article, we review on-label indications and off-label uses for apremilast; highlight the importance of apremilast for managing psoriasis in the military population; and propose other patient populations in whom the use of apremilast is favorable. We also present a case report that highlights and embodies the benefit of apremilast for military service members.

CASE REPORT

A 28-year-old active-duty male US Navy service member developed extensive guttate psoriasis in a distribution too wide to manage with topical medication (Figure, A–C). His condition did not improve with a trial of oral antibiotics, and he reported itch that affected his sleep. He denied new joint pain, swelling, or deformity.

A review of the patient’s service history revealed that he was serving aboard a guided-missile cruiser ship for a tour extending an additional 2 years. Limited medical resources and lack of refrigeration made the use of injectable biologics, such as adalimumab, infeasible. Furthermore, the patient was too critical to the mission to be transported frequently off the ship to a higher level of care for injection of medication. He also had trouble returning for appointments and refills because of the high operational tempo of his command.

After discussion with the patient, oral apremilast was started at 30 mg/d and titrated up to the standard dosing of 30 mg twice daily, with excellent results by 3 months after he started therapy (Figure, D–F).

COMMENT

We reviewed the research on apremilast for its approved indications, including psoriasis; its off-label uses; and strategies for using the drug to treat psoriasis and other dermatologic conditions in military populations. The most recent evidence regarding the use of apremilast in dermatology, rheumatology, and other medical specialties was assessed using published English-language research data and review articles. We conducted a PubMed search of articles indexed for MEDLINE using the following terms: apremilast, Otezla, psoriasis, psoriatic arthritis, arthritis, off-label, Behçet’s, hidradenitis suppurativa, military, and armed forces. We also reviewed citations within relevant articles to identify additional relevant sources.

Off-label uses reviewed here are based on data from randomized controlled trials, large open-label trials, and large prospective case series. Articles with less evidence are not included in this review.

On-Label Usage Profile

Apremilast is an orally administered, small-molecule inhibitor of phosphodiesterase 4. Small-molecule inhibitors are a class of medications with low molecular weight, high stability, and short half-life. They act intracellularly to modulate proinflammatory states through regulation of the proinflammatory cytokine milieu.

Apremilast has been approved by the FDA for use in adult psoriasis and psoriatic arthritis since 2014 and for use in treating oral ulcers of Behçet disease since 2019.^1-3,5,6 Recently, a phase 2, multicenter, open-label study on the use of apremilast in pediatric psoriasis patients (aged 12–17 years) demonstrated a similar safety profile with weight-based dosing⁸; phase 3 trials in this population are in the recruitment phase (ClinicalTrials.gov Identifier NCT03701763).

Because information regarding its use in pregnancy is limited, apremilast is not recommended in this population. It is unknown whether apremilast is present in breast milk; although the manufacturer does not make explicit recommendations regarding use during breastfeeding, an expert panel reviewing management of psoriasis in pregnant and breastfeeding women recommended avoiding its use while breastfeeding.⁹

Common Adverse Effects

Common adverse effects (AEs) include weight loss (>5% total body weight in 5% of patients; 5%–10% of total body weight in 10%–12% of patients; and ≥10% total body weight in 2% of patients), diarrhea and nausea, headache, and upper respiratory tract infection.^10,11 Gastrointestinal AEs tend to be self-limited and improve or resolve after the first few weeks of therapy. Caution is advised in patients older than 65 years and in those at risk for hypotension or volume depletion. Although depressed mood is a rare AE (<1%), apremilast should be used cautiously in patients with a history of depression or suicidal ideation. Weight loss generally is self-limited; routine monitoring of weight is recommended.¹¹

Apremilast in Psoriasis and Psoriatic Arthritis

Psoriasis
The ESTEEM trials established the safety and efficacy of apremilast for use in psoriasis.^2,3 In a phase 3, multicenter, double-blind, placebo-controlled trial of 844 patients, apremilast demonstrated a statistically significant 75% or greater reduction from the baseline psoriasis area and severity index score (PASI-75) in 33.1% of patients receiving the medication compared to 5.3% of those receiving placebo.² Data from real-world practice (outside constraints of clinical trials) suggest slightly greater efficacy than was demonstrated in the ESTEEM trials.

A recently published retrospective, cross-sectional study of 480 patients with psoriasis treated with apremilast reported that 48.6% of patients continuing therapy for a mean (SD) of 6 (1) months achieved PASI-75. Furthermore, the mean dermatology life quality index (DLQI) score of the surveyed population decreased from 13.4 at initiation of treatment to 5.7 at 6 (1) months of treatment—a marked improvement in quality of life.¹² Other single-center and smaller study populations also have suggested increased real-world benefit.^13,14

Nonetheless, the rate and degree of clearance of plaques with apremilast seem to lag behind what is observed with many of the biologics and traditional medications employed to treat psoriasis.^15-19 Furthermore, indirect cost analysis comparisons suggest a much higher cost per level of PASI for apremilast compared to several biologics and to methotrexate.^20,21 A study that used indirect methods of comparison to analyze the comparative cost and efficacy of apremilast and methotrexate found no evidence of greater efficacy for apremilast and that the incremental cost to achieve 1 additional PASI-75 responder by using apremilast is $187,888 annually.²¹

Psoriatic Arthritis
The PALACE clinical trials 1, 2, and 3 assessed the efficacy of apremilast in patients who had prior treatment with conventional disease-modifying antirheumatic drugs or biologics, or both. PALACE 4 evaluated efficacy in treatment-naïve patients; standard dosing of apremilast was found to produce improvement in psoriatic arthritis in treatment-naïve and non–treatment-naïve patients.^4-6,22 In the 24-week placebo-controlled phase of the PALACE 1 trial, the American College of Rheumatology (ACR) baseline composite measurement of 20% disease improvement, or ACR20, was achieved in 40% of patients randomized to the standard dosing regimen compared to 19% of patients receiving placebo, a statistically significant result (P<.001).²²

Evaluation of long-term study data is beyond the scope of this review, but those data suggest that disease outcomes continue to improve the longer therapy is utilized, with a greater percentage of patients achieving ACR20 as well as ACR50 (50% improvement) and ACR70 (70% improvement) responses. Indirect comparisons analyzing the cost and effectiveness for adalimumab, apremilast, and methotrexate in patients with psoriatic arthritis found that apremilast was less effective than adalimumab and as efficacious as methotrexate, though apremilast carries the highest price tag of these drugs.²³

Off-Label Uses

Ease of oral administration and a favorable safety profile have prompted off-label study of apremilast in other inflammatory skin diseases, including atopic dermatitis, hidradenitis suppurativa, lichen planus, rosacea, alopecia areata, and cutaneous sarcoidosis. Publications with a minimum case series of 10 patients are included in the Table.^24-32

Use in the Military and Beyond

Psoriasis and other inflammatory skin conditions are common in the military and can greatly hinder a service member’s ability to perform their duties and remain ready to deploy. A history of psoriasis is disqualifying for military recruits, but early entry into service, misdiagnosis, and low or no burden of disease at time of entry into the service all contribute to a substantial population of active-duty service members who require treatment of psoriasis.³³ Necessity dictates that treatment of this condition extend to theater operations; from 2008 to 2015, more than 3600 soldiers sought care for psoriasis while deployed to a combat theater.³⁴

In some cases, poorly controlled inflammatory skin conditions lead to medical separation.³³ Although there are limited data on the use of apremilast in the military, its use during deployment for the treatment of psoriasis and psoriatic arthritis has been reported, with the great majority of service members retaining their deployable status even 1 year after the study period.³⁵

The ideal medication for deployable military personnel should have low toxicity, simple storage, and minimal monitoring requirements, and it should not expose a service member to increased risk while in a combat theater. Worldwide deployability is a requirement for most military occupations. The risk for immunosuppression with targeted immune therapy must be fully weighed, as certain duty stations and deployments might increase the risk for exposure to Mycobacterium tuberculosis, endemic mycopathogens, hepatitis C virus, HIV, Leishmania, and Strongyloides.³⁴

Furthermore, the tumor necrosis factor α inhibitors and IL-17 and IL-23 blockers used to treat psoriasis all require refrigeration; often, this requirement cannot be met in austere overseas settings. Additional requirements for laboratory monitoring, titration of medications, and frequent office visits might prohibit a service member from performing their duties, which, in turn, is detrimental to military readiness and the career of that service member.

Last, the Centers for Disease Control and Prevention recommend avoiding live virus vaccination while taking targeted immune therapy because of safety and effectiveness concerns during immunosuppression.³⁶ This recommendation might disqualify military personnel from deployment to certain locations that require the protection that such vaccines afford. Therefore, apremilast is an ideal option for the military patient population, with many military-specific advantages.

Of course, the military is not the only population in whom ease of use and storage and simplified monitoring parameters are essential. Benefits of apremilast also may translate to patients who are placed in austere conditions or who participate in extended worldwide travel for work or leisure, such as government contractors who deploy in support of military operations, firefighters or national park employees who spend extended periods in resource-limited settings, and foreign-aid workers and diplomats who are engaged in frequent travel around the world. Furthermore, travel to certain regions might increase the risk for exposure to atypical pathogens as well as the desire for a therapeutic option that does not have potential to suppress the immune system. This subset of psoriasis patients might be better treated with novel agents such as apremilast than other drugs that would be the presumed standard of care in a domestic setting.

Final Thoughts

The benefits of apremilast translate to all patients in austere environments with limited resources and during times when immune function is of utmost concern. For military service members and many civilians in austere environments worldwide, apremilast could be considered a first-line systemic agent for psoriasis and psoriatic arthritis. In patients unable to use or tolerate other treatments, apremilast can be considered for off-label therapy (Table^24-32). There are times when the approach to prescribing must look beyond primary efficacy, AE profile, and cost—to include occupation, environment, or duties—to select the optimal medication for a patient.

Itch is one of the most protean manifestations of skin disease and can take a substantial physical and emotional toll on patients. For physicians, it is a frequent—if often dreaded—patient concern with a rising incidence. Lack of specific itch therapies as well as associations with multiple dermatologic conditions, including xerosis, psoriasis, atopic dermatitis, cutaneous lymphoma, contact dermatitis, and internal malignancies, make management of these itchy patients challenging and deserving of our attention. Studies evaluating patients with chronic pruritus identified a considerable impact on health-related quality of life, including development of depression, inability to perform activities of daily living, and sleep difficulties. ¹

How to Classify Itching

Itch, or pruritus, originally was defined as an unpleasant sensation that provokes the desire to scratch,² but this definition likely limits our ability to assess itch. The urge to scratch the skin to relieve the itch is sometimes a reflex of the muscles triggered by the spinal cord that can be either conscious or unconscious. If 2 patients present with itch, does the patient with more excoriated skin experience more severe itch? Conversely, does the patient who scratches less have an equivalent decrease in itch severity? Although it is tempting to quantify itch through physical signs such as excoriations, it ultimately is a subjective symptom that is difficult to assess.

Pain is another complex subjective symptom but is one that has been better studied. A previous intensity theory postulated that itch is a form of pain: low-intensity noxious stimuli are perceived as itch, while high-intensity stimuli are perceived as pain. Over time, our understanding of itch evolved, and it became clear that a specific neuronal pathway for itch also exists.³ However, the pathophysiology of itch and pain remain intertwined. Scratching may elicit pain, providing a change in sensation that replaces the itch, whereas opioid analgesics suppress pain but may worsen the itch.

We are gaining a better understanding of the biology and classification of itch, which will hopefully enable the development of new measures to accurately assess itch. Four main categories of itch currently exist: neurogenic, psychogenic, neuropathic, and pruritoceptive.⁴ Patients may have one or multiple types of itch, which can be differentiated clinically and biochemically. Neurogenic (also known as systemic) itch is transmitted via the central nervous system with possible involvement of itch-specific neurons in the spinal cord and encompasses itch associated with pruritus from other organ systems. As the term implies, psychogenic itch is associated with psychiatric disorders. Neuropathic itch is generated from the inappropriate firing of peripheral or central sensory neurons in the absence of pruritogenic stimuli, which can be seen in notalgia paresthetica, brachioradial pruritus, and postherpetic neuralgia. Pruritoceptive itch most commonly is encountered in dermatology and is associated with skin inflammation or other dermatoses.⁴

How to Assess Itch Quantitatively

There currently are 2 major questions about quantitative assessments of itch. First, how do we measure itch in studies that are designed to relieve a different skin disease that is associated with itch? Most clinical trials investigating therapeutic options for atopic dermatitis and psoriasis now include itch assessment and improvement as a secondary outcome. Second, how do we measure itch in studies that are designed with relief of itch as the primary end point? Both of these scenarios require a fundamental set of decisions. Itch clearly is a subjective experience, but it also is one that can be local, regional, generalized, or transitory. Just as with pain, an individual can be distracted from their itch to some extent and consequently experience it more acutely when there are fewer stimuli in their environment. Classically, patients will report that itching is worse at night, preventing them from sleeping. Sleep disruption previously has been demonstrated.⁵ Of course, the environment also can exacerbate itch, as dry air and in some cases humidity can flare the sensation.

Fundamentally, therefore, the questions that are asked to assess itch are incredibly relevant, and there is a matrix of possible avenues of inquiry. Should you measure the peak itch in one area or the peak itch overall? Is the duration, the frequency, or the persistence of the itching most relevant? What is the correct time frame in which to do an assessment: the last 24 hours, the last 48 hours, or the last week? Because these parameters have been so challenging, most investigators have used a visual analog scale, similar to what is used to assess pain, at a 24-hour interval to decrease recall bias. The most commonly employed tool is the itch numeric rating scale (NRS), which asks patients to rate their symptoms on a scale of 0 (no itch) to 10 (worst imaginable itch). Although the psychometric properties of the itch NRS have been validated, debate still exists as to whether the itch NRS is best administered at a specific time of day or if it should be updated to evaluate peak pruritus scores explicitly. Regardless, implementing these scales often is time consuming and burdensome in the clinical trial setting, as participants are asked to complete daily diaries at the same time each day using either paper forms or electronic tablets.

Once scores are collected, we then need to quantitate a meaningful difference in itch. For pain, there has been some acceptance of a 30% difference, or a 2-point reduction, as being clinically meaningful; however, there was substantial debate at the time of the approval of ixekizumab as to whether that was a similarly appropriate threshold for itch. Using data from ixekizumab phase 2 and phase 3 trials, a 4-point reduction in itch NRS was found to be optimal for evaluating clinically significant changes in moderate to severe psoriasis.⁶ A more recent study of the validity of the itch NRS in prurigo nodularis suggested a 1-point change was correlated with minimal clinical improvement.⁷ Thus, the interesting question of how assessment of itch varies across clinical trials and disease states needs to be raised. Psoriasis classically has been thought of as not particularly itchy, and atopic dermatitis and prurigo nodularis have been regarded as extraordinarily itchy, yet one study comparing baseline itch scores in psoriasis and atopic dermatitis suggested that the experience actually is somewhat similar.⁸

Final Thoughts

The subjective nature of itch makes NRSs our best option at this time, but the best disease severity assessment tools are objective, sensitive, and generalizable. Unfortunately, we do not have such tools available to us yet, but technology—smart devices to monitor nocturnal scratching and machine learning algorithms that use electromagnetic impact to capture motion associated with itching and scratching⁹—may offer new objective measures for itch that can be used to further validate the current itch NRS. Even if these technology-based approaches become the standard of measurement, they will certainly help us understand what we are measuring. And even better, the focus on how to develop meaningful end points around the improvement of itch will likely lead us to measure it more and drive the development of therapeutics that address the effect and consequences of this pernicious problem.

Itch is one of the most protean manifestations of skin disease and can take a substantial physical and emotional toll on patients. For physicians, it is a frequent—if often dreaded—patient concern with a rising incidence. Lack of specific itch therapies as well as associations with multiple dermatologic conditions, including xerosis, psoriasis, atopic dermatitis, cutaneous lymphoma, contact dermatitis, and internal malignancies, make management of these itchy patients challenging and deserving of our attention. Studies evaluating patients with chronic pruritus identified a considerable impact on health-related quality of life, including development of depression, inability to perform activities of daily living, and sleep difficulties. ¹

How to Classify Itching

Itch, or pruritus, originally was defined as an unpleasant sensation that provokes the desire to scratch,² but this definition likely limits our ability to assess itch. The urge to scratch the skin to relieve the itch is sometimes a reflex of the muscles triggered by the spinal cord that can be either conscious or unconscious. If 2 patients present with itch, does the patient with more excoriated skin experience more severe itch? Conversely, does the patient who scratches less have an equivalent decrease in itch severity? Although it is tempting to quantify itch through physical signs such as excoriations, it ultimately is a subjective symptom that is difficult to assess.

Pain is another complex subjective symptom but is one that has been better studied. A previous intensity theory postulated that itch is a form of pain: low-intensity noxious stimuli are perceived as itch, while high-intensity stimuli are perceived as pain. Over time, our understanding of itch evolved, and it became clear that a specific neuronal pathway for itch also exists.³ However, the pathophysiology of itch and pain remain intertwined. Scratching may elicit pain, providing a change in sensation that replaces the itch, whereas opioid analgesics suppress pain but may worsen the itch.

We are gaining a better understanding of the biology and classification of itch, which will hopefully enable the development of new measures to accurately assess itch. Four main categories of itch currently exist: neurogenic, psychogenic, neuropathic, and pruritoceptive.⁴ Patients may have one or multiple types of itch, which can be differentiated clinically and biochemically. Neurogenic (also known as systemic) itch is transmitted via the central nervous system with possible involvement of itch-specific neurons in the spinal cord and encompasses itch associated with pruritus from other organ systems. As the term implies, psychogenic itch is associated with psychiatric disorders. Neuropathic itch is generated from the inappropriate firing of peripheral or central sensory neurons in the absence of pruritogenic stimuli, which can be seen in notalgia paresthetica, brachioradial pruritus, and postherpetic neuralgia. Pruritoceptive itch most commonly is encountered in dermatology and is associated with skin inflammation or other dermatoses.⁴

How to Assess Itch Quantitatively

There currently are 2 major questions about quantitative assessments of itch. First, how do we measure itch in studies that are designed to relieve a different skin disease that is associated with itch? Most clinical trials investigating therapeutic options for atopic dermatitis and psoriasis now include itch assessment and improvement as a secondary outcome. Second, how do we measure itch in studies that are designed with relief of itch as the primary end point? Both of these scenarios require a fundamental set of decisions. Itch clearly is a subjective experience, but it also is one that can be local, regional, generalized, or transitory. Just as with pain, an individual can be distracted from their itch to some extent and consequently experience it more acutely when there are fewer stimuli in their environment. Classically, patients will report that itching is worse at night, preventing them from sleeping. Sleep disruption previously has been demonstrated.⁵ Of course, the environment also can exacerbate itch, as dry air and in some cases humidity can flare the sensation.

Fundamentally, therefore, the questions that are asked to assess itch are incredibly relevant, and there is a matrix of possible avenues of inquiry. Should you measure the peak itch in one area or the peak itch overall? Is the duration, the frequency, or the persistence of the itching most relevant? What is the correct time frame in which to do an assessment: the last 24 hours, the last 48 hours, or the last week? Because these parameters have been so challenging, most investigators have used a visual analog scale, similar to what is used to assess pain, at a 24-hour interval to decrease recall bias. The most commonly employed tool is the itch numeric rating scale (NRS), which asks patients to rate their symptoms on a scale of 0 (no itch) to 10 (worst imaginable itch). Although the psychometric properties of the itch NRS have been validated, debate still exists as to whether the itch NRS is best administered at a specific time of day or if it should be updated to evaluate peak pruritus scores explicitly. Regardless, implementing these scales often is time consuming and burdensome in the clinical trial setting, as participants are asked to complete daily diaries at the same time each day using either paper forms or electronic tablets.

Once scores are collected, we then need to quantitate a meaningful difference in itch. For pain, there has been some acceptance of a 30% difference, or a 2-point reduction, as being clinically meaningful; however, there was substantial debate at the time of the approval of ixekizumab as to whether that was a similarly appropriate threshold for itch. Using data from ixekizumab phase 2 and phase 3 trials, a 4-point reduction in itch NRS was found to be optimal for evaluating clinically significant changes in moderate to severe psoriasis.⁶ A more recent study of the validity of the itch NRS in prurigo nodularis suggested a 1-point change was correlated with minimal clinical improvement.⁷ Thus, the interesting question of how assessment of itch varies across clinical trials and disease states needs to be raised. Psoriasis classically has been thought of as not particularly itchy, and atopic dermatitis and prurigo nodularis have been regarded as extraordinarily itchy, yet one study comparing baseline itch scores in psoriasis and atopic dermatitis suggested that the experience actually is somewhat similar.⁸

Final Thoughts

The subjective nature of itch makes NRSs our best option at this time, but the best disease severity assessment tools are objective, sensitive, and generalizable. Unfortunately, we do not have such tools available to us yet, but technology—smart devices to monitor nocturnal scratching and machine learning algorithms that use electromagnetic impact to capture motion associated with itching and scratching⁹—may offer new objective measures for itch that can be used to further validate the current itch NRS. Even if these technology-based approaches become the standard of measurement, they will certainly help us understand what we are measuring. And even better, the focus on how to develop meaningful end points around the improvement of itch will likely lead us to measure it more and drive the development of therapeutics that address the effect and consequences of this pernicious problem.

Itch is one of the most protean manifestations of skin disease and can take a substantial physical and emotional toll on patients. For physicians, it is a frequent—if often dreaded—patient concern with a rising incidence. Lack of specific itch therapies as well as associations with multiple dermatologic conditions, including xerosis, psoriasis, atopic dermatitis, cutaneous lymphoma, contact dermatitis, and internal malignancies, make management of these itchy patients challenging and deserving of our attention. Studies evaluating patients with chronic pruritus identified a considerable impact on health-related quality of life, including development of depression, inability to perform activities of daily living, and sleep difficulties. ¹

How to Classify Itching

Itch, or pruritus, originally was defined as an unpleasant sensation that provokes the desire to scratch,² but this definition likely limits our ability to assess itch. The urge to scratch the skin to relieve the itch is sometimes a reflex of the muscles triggered by the spinal cord that can be either conscious or unconscious. If 2 patients present with itch, does the patient with more excoriated skin experience more severe itch? Conversely, does the patient who scratches less have an equivalent decrease in itch severity? Although it is tempting to quantify itch through physical signs such as excoriations, it ultimately is a subjective symptom that is difficult to assess.

Pain is another complex subjective symptom but is one that has been better studied. A previous intensity theory postulated that itch is a form of pain: low-intensity noxious stimuli are perceived as itch, while high-intensity stimuli are perceived as pain. Over time, our understanding of itch evolved, and it became clear that a specific neuronal pathway for itch also exists.³ However, the pathophysiology of itch and pain remain intertwined. Scratching may elicit pain, providing a change in sensation that replaces the itch, whereas opioid analgesics suppress pain but may worsen the itch.

We are gaining a better understanding of the biology and classification of itch, which will hopefully enable the development of new measures to accurately assess itch. Four main categories of itch currently exist: neurogenic, psychogenic, neuropathic, and pruritoceptive.⁴ Patients may have one or multiple types of itch, which can be differentiated clinically and biochemically. Neurogenic (also known as systemic) itch is transmitted via the central nervous system with possible involvement of itch-specific neurons in the spinal cord and encompasses itch associated with pruritus from other organ systems. As the term implies, psychogenic itch is associated with psychiatric disorders. Neuropathic itch is generated from the inappropriate firing of peripheral or central sensory neurons in the absence of pruritogenic stimuli, which can be seen in notalgia paresthetica, brachioradial pruritus, and postherpetic neuralgia. Pruritoceptive itch most commonly is encountered in dermatology and is associated with skin inflammation or other dermatoses.⁴

How to Assess Itch Quantitatively

There currently are 2 major questions about quantitative assessments of itch. First, how do we measure itch in studies that are designed to relieve a different skin disease that is associated with itch? Most clinical trials investigating therapeutic options for atopic dermatitis and psoriasis now include itch assessment and improvement as a secondary outcome. Second, how do we measure itch in studies that are designed with relief of itch as the primary end point? Both of these scenarios require a fundamental set of decisions. Itch clearly is a subjective experience, but it also is one that can be local, regional, generalized, or transitory. Just as with pain, an individual can be distracted from their itch to some extent and consequently experience it more acutely when there are fewer stimuli in their environment. Classically, patients will report that itching is worse at night, preventing them from sleeping. Sleep disruption previously has been demonstrated.⁵ Of course, the environment also can exacerbate itch, as dry air and in some cases humidity can flare the sensation.

Fundamentally, therefore, the questions that are asked to assess itch are incredibly relevant, and there is a matrix of possible avenues of inquiry. Should you measure the peak itch in one area or the peak itch overall? Is the duration, the frequency, or the persistence of the itching most relevant? What is the correct time frame in which to do an assessment: the last 24 hours, the last 48 hours, or the last week? Because these parameters have been so challenging, most investigators have used a visual analog scale, similar to what is used to assess pain, at a 24-hour interval to decrease recall bias. The most commonly employed tool is the itch numeric rating scale (NRS), which asks patients to rate their symptoms on a scale of 0 (no itch) to 10 (worst imaginable itch). Although the psychometric properties of the itch NRS have been validated, debate still exists as to whether the itch NRS is best administered at a specific time of day or if it should be updated to evaluate peak pruritus scores explicitly. Regardless, implementing these scales often is time consuming and burdensome in the clinical trial setting, as participants are asked to complete daily diaries at the same time each day using either paper forms or electronic tablets.

Once scores are collected, we then need to quantitate a meaningful difference in itch. For pain, there has been some acceptance of a 30% difference, or a 2-point reduction, as being clinically meaningful; however, there was substantial debate at the time of the approval of ixekizumab as to whether that was a similarly appropriate threshold for itch. Using data from ixekizumab phase 2 and phase 3 trials, a 4-point reduction in itch NRS was found to be optimal for evaluating clinically significant changes in moderate to severe psoriasis.⁶ A more recent study of the validity of the itch NRS in prurigo nodularis suggested a 1-point change was correlated with minimal clinical improvement.⁷ Thus, the interesting question of how assessment of itch varies across clinical trials and disease states needs to be raised. Psoriasis classically has been thought of as not particularly itchy, and atopic dermatitis and prurigo nodularis have been regarded as extraordinarily itchy, yet one study comparing baseline itch scores in psoriasis and atopic dermatitis suggested that the experience actually is somewhat similar.⁸

Final Thoughts

The subjective nature of itch makes NRSs our best option at this time, but the best disease severity assessment tools are objective, sensitive, and generalizable. Unfortunately, we do not have such tools available to us yet, but technology—smart devices to monitor nocturnal scratching and machine learning algorithms that use electromagnetic impact to capture motion associated with itching and scratching⁹—may offer new objective measures for itch that can be used to further validate the current itch NRS. Even if these technology-based approaches become the standard of measurement, they will certainly help us understand what we are measuring. And even better, the focus on how to develop meaningful end points around the improvement of itch will likely lead us to measure it more and drive the development of therapeutics that address the effect and consequences of this pernicious problem.

Patients being treated with infliximab had weakened immune responses to the first dose of the ChAdOx1 nCoV-19 (Oxford/AstraZeneca) and BNT162b2 (Pfizer/BioNTech) vaccines, compared with patients on vedolizumab (Entyvio), although a very significant number of patients from both groups seroconverted after their second dose, according to a new U.K. study of patients with inflammatory bowel disease (IBD).

NoSystem images/Getty Images

“Antibody testing and adapted vaccine schedules should be considered to protect these at-risk patients,” Nicholas A. Kennedy, PhD, MBBS, of the University of Exeter (England) and colleagues wrote in a preprint published March 29 on MedRxiv.

Infliximab is an anti–tumor necrosis factor (anti-TNF) monoclonal antibody that’s approved to treat adult and pediatric Crohn’s disease and ulcerative colitis, as well as rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis, whereas vedolizumab, a gut selective anti-integrin alpha4beta7 monoclonal antibody that is not associated with impaired systemic immune responses, is approved to treat Crohn’s disease and ulcerative colitis in adults.

A previous study from Kennedy and colleagues revealed that IBD patients on infliximab showed a weakened COVID-19 antibody response compared with patients on vedolizumab. To determine if treatment with anti-TNF drugs impacted the efficacy of the first shot of these two-dose COVID-19 vaccines, the researchers used data from the CLARITY IBD study to assess 865 infliximab- and 428 vedolizumab-treated participants without evidence of prior SARS-CoV-2 infection who had received uninterrupted biologic therapy since being recruited between Sept. 22 and Dec. 23, 2020.

In the 3-10 weeks after initial vaccination, geometric mean concentrations for SARS-CoV-2 anti-spike protein receptor-binding protein antibodies were lower in patients on infliximab, compared with patients on vedolizumab for both the Pfizer (6.0 U/mL [5.9] versus 28.8 U/mL [5.4], P < .0001) and AstraZeneca (4.7 U/mL [4.9] versus 13.8 U/mL [5.9]; P < .0001) vaccines. The researchers’ multivariable models reinforced those findings, with antibody concentrations lower in infliximab-treated patients for both the Pfizer (fold change, 0.29; 95% confidence interval, 0.21-0.40; P < .0001) and AstraZeneca (FC, 0.39; 95% CI, 0.30-0.51; P < .0001) vaccines.

After second doses of the two-dose Pfizer vaccine, 85% of patients on infliximab and 86% of patients on vedolizumab seroconverted (P = .68); similarly high seroconversion rates were seen in patients who had been infected with SARS-CoV-2 prior to receiving either vaccine. Several patient characteristics were associated with lower antibody concentrations regardless of vaccine type: being 60 years or older, use of immunomodulators, having Crohn’s disease, and being a smoker. Alternatively, non-White ethnicity was associated with higher antibody concentrations.

Evidence has ‘unclear clinical significance’

“These data, which require peer review, do not change my opinion on the safety and efficacy of COVID-19 vaccines in patients taking TNF inhibitors such as infliximab as monotherapy for the treatment of psoriatic disease,” Joel M. Gelfand MD, director of the psoriasis and phototherapy treatment center at the University of Pennsylvania, Philadelphia, said in an interview.

Courtesy Dr. Joel M. Gelfand

“First, two peer-reviewed studies found good antibody response in patients on TNF inhibitors receiving COVID-19 vaccines (doi: 10.1136/annrheumdis-2021-220289; 10.1136/annrheumdis-2021-220272). Second, antibody responses were robust in the small cohort that received the second dose of a COVID-19 vaccine. We already know that, for the two messenger RNA-based vaccines available under emergency use authorization in the U.S., a second dose is required for optimal efficacy. Thus, evidence of a reduced antibody response after just one dose is of unclear clinical significance. Third, antibody responses are only a surrogate marker, and a low antibody response doesn’t necessarily mean the patient will not be protected by the vaccine.”
 

Focus on the second dose of a two-dose regimen

“Tell me about the response in people who got both doses of a vaccine that you’re supposed to get both doses of,” Jeffrey Curtis, MD, professor of medicine in the division of clinical immunology and rheumatology at the University of Alabama at Birmingham, said in an interview. “The number of patients in that subset was small [n = 27] but in my opinion that’s the most clinically relevant analysis and the one that patients and clinicians want answered.”

Courtesy UAB Photo

He also emphasized the uncertainty around what ‘protection’ means in these early days of studying COVID-19 vaccine responses. “You can define seroprotection or seroconversion as some absolute level of an antibody response, but if you want to say ‘Mrs. Smith, your antibody level was X,’ on whatever arbitrary scale with whoever’s arbitrary lab test, nobody actually knows that Mrs. Smith is now protected from SARS-CoV-2, or how protected,” he said.

“What is not terribly controversial is: If you can’t detect antibodies, the vaccine didn’t ‘take,’ if you will. But if I tell you that the mean antibody level was X with one drug and then 2X with another drug, does that mean that you’re twice as protected? We don’t know that. I’m fearful that people are looking at these studies and thinking that more is better. It might be, but we don’t know that to be true.”
 

Debating the cause of weakened immune responses

“The biological plausibility of being on an anti-TNF affecting your immune reaction to a messenger RNA or even a replication-deficient viral vector vaccine doesn’t make sense,” David T. Rubin, MD, professor of medicine at the University of Chicago and chair of the National Scientific Advisory Committee of the Crohn’s and Colitis Foundation, said in an interview.

“I’m sure immunologists may differ with me on this, but given what we have come to appreciate about these vaccine mechanisms, this finding doesn’t make intuitive sense. So we need to make sure that, when this happens, we look to the next studies and try to understand, was there any other confounder that may have resulted in these findings that was not adequately adjusted for or addressed in some other way?

“When you have a study of this size, you argue, ‘Because it’s so large, any effect that was seen must be real,’ ” he added. “Alternatively, to have a study of this size, by its very nature you are limited in being able to control for certain other factors or differences between the groups.”

That said, he commended the authors for their study and acknowledged the potential questions it raises about the single-shot Johnson & Johnson vaccine. “If you only get one and you’re on infliximab, this study implies that maybe that’s not enough,” he said. “Despite the fact that Johnson & Johnson was approved as a single dose, it may be necessary to think about it as the first of two, or maybe it’s not the preferred vaccine in this group of patients.”

The study was supported by the Royal Devon and Exeter and Hull University Hospital Foundation NHS Trusts and unrestricted educational grants from Biogen (Switzerland), Celltrion Healthcare (South Korea), Galapagos NV (Belgium), and F. Hoffmann-La Roche (Switzerland). The authors acknowledged numerous potential conflicts of interest, including receiving grants, personal fees, and nonfinancial support from various pharmaceutical companies.

Patients being treated with infliximab had weakened immune responses to the first dose of the ChAdOx1 nCoV-19 (Oxford/AstraZeneca) and BNT162b2 (Pfizer/BioNTech) vaccines, compared with patients on vedolizumab (Entyvio), although a very significant number of patients from both groups seroconverted after their second dose, according to a new U.K. study of patients with inflammatory bowel disease (IBD).

NoSystem images/Getty Images

“Antibody testing and adapted vaccine schedules should be considered to protect these at-risk patients,” Nicholas A. Kennedy, PhD, MBBS, of the University of Exeter (England) and colleagues wrote in a preprint published March 29 on MedRxiv.

Infliximab is an anti–tumor necrosis factor (anti-TNF) monoclonal antibody that’s approved to treat adult and pediatric Crohn’s disease and ulcerative colitis, as well as rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis, whereas vedolizumab, a gut selective anti-integrin alpha4beta7 monoclonal antibody that is not associated with impaired systemic immune responses, is approved to treat Crohn’s disease and ulcerative colitis in adults.

A previous study from Kennedy and colleagues revealed that IBD patients on infliximab showed a weakened COVID-19 antibody response compared with patients on vedolizumab. To determine if treatment with anti-TNF drugs impacted the efficacy of the first shot of these two-dose COVID-19 vaccines, the researchers used data from the CLARITY IBD study to assess 865 infliximab- and 428 vedolizumab-treated participants without evidence of prior SARS-CoV-2 infection who had received uninterrupted biologic therapy since being recruited between Sept. 22 and Dec. 23, 2020.

In the 3-10 weeks after initial vaccination, geometric mean concentrations for SARS-CoV-2 anti-spike protein receptor-binding protein antibodies were lower in patients on infliximab, compared with patients on vedolizumab for both the Pfizer (6.0 U/mL [5.9] versus 28.8 U/mL [5.4], P < .0001) and AstraZeneca (4.7 U/mL [4.9] versus 13.8 U/mL [5.9]; P < .0001) vaccines. The researchers’ multivariable models reinforced those findings, with antibody concentrations lower in infliximab-treated patients for both the Pfizer (fold change, 0.29; 95% confidence interval, 0.21-0.40; P < .0001) and AstraZeneca (FC, 0.39; 95% CI, 0.30-0.51; P < .0001) vaccines.

After second doses of the two-dose Pfizer vaccine, 85% of patients on infliximab and 86% of patients on vedolizumab seroconverted (P = .68); similarly high seroconversion rates were seen in patients who had been infected with SARS-CoV-2 prior to receiving either vaccine. Several patient characteristics were associated with lower antibody concentrations regardless of vaccine type: being 60 years or older, use of immunomodulators, having Crohn’s disease, and being a smoker. Alternatively, non-White ethnicity was associated with higher antibody concentrations.

Evidence has ‘unclear clinical significance’

“These data, which require peer review, do not change my opinion on the safety and efficacy of COVID-19 vaccines in patients taking TNF inhibitors such as infliximab as monotherapy for the treatment of psoriatic disease,” Joel M. Gelfand MD, director of the psoriasis and phototherapy treatment center at the University of Pennsylvania, Philadelphia, said in an interview.

Courtesy Dr. Joel M. Gelfand

“First, two peer-reviewed studies found good antibody response in patients on TNF inhibitors receiving COVID-19 vaccines (doi: 10.1136/annrheumdis-2021-220289; 10.1136/annrheumdis-2021-220272). Second, antibody responses were robust in the small cohort that received the second dose of a COVID-19 vaccine. We already know that, for the two messenger RNA-based vaccines available under emergency use authorization in the U.S., a second dose is required for optimal efficacy. Thus, evidence of a reduced antibody response after just one dose is of unclear clinical significance. Third, antibody responses are only a surrogate marker, and a low antibody response doesn’t necessarily mean the patient will not be protected by the vaccine.”
 

Focus on the second dose of a two-dose regimen

“Tell me about the response in people who got both doses of a vaccine that you’re supposed to get both doses of,” Jeffrey Curtis, MD, professor of medicine in the division of clinical immunology and rheumatology at the University of Alabama at Birmingham, said in an interview. “The number of patients in that subset was small [n = 27] but in my opinion that’s the most clinically relevant analysis and the one that patients and clinicians want answered.”

Courtesy UAB Photo

He also emphasized the uncertainty around what ‘protection’ means in these early days of studying COVID-19 vaccine responses. “You can define seroprotection or seroconversion as some absolute level of an antibody response, but if you want to say ‘Mrs. Smith, your antibody level was X,’ on whatever arbitrary scale with whoever’s arbitrary lab test, nobody actually knows that Mrs. Smith is now protected from SARS-CoV-2, or how protected,” he said.

“What is not terribly controversial is: If you can’t detect antibodies, the vaccine didn’t ‘take,’ if you will. But if I tell you that the mean antibody level was X with one drug and then 2X with another drug, does that mean that you’re twice as protected? We don’t know that. I’m fearful that people are looking at these studies and thinking that more is better. It might be, but we don’t know that to be true.”
 

Debating the cause of weakened immune responses

“The biological plausibility of being on an anti-TNF affecting your immune reaction to a messenger RNA or even a replication-deficient viral vector vaccine doesn’t make sense,” David T. Rubin, MD, professor of medicine at the University of Chicago and chair of the National Scientific Advisory Committee of the Crohn’s and Colitis Foundation, said in an interview.

“I’m sure immunologists may differ with me on this, but given what we have come to appreciate about these vaccine mechanisms, this finding doesn’t make intuitive sense. So we need to make sure that, when this happens, we look to the next studies and try to understand, was there any other confounder that may have resulted in these findings that was not adequately adjusted for or addressed in some other way?

“When you have a study of this size, you argue, ‘Because it’s so large, any effect that was seen must be real,’ ” he added. “Alternatively, to have a study of this size, by its very nature you are limited in being able to control for certain other factors or differences between the groups.”

That said, he commended the authors for their study and acknowledged the potential questions it raises about the single-shot Johnson & Johnson vaccine. “If you only get one and you’re on infliximab, this study implies that maybe that’s not enough,” he said. “Despite the fact that Johnson & Johnson was approved as a single dose, it may be necessary to think about it as the first of two, or maybe it’s not the preferred vaccine in this group of patients.”

The study was supported by the Royal Devon and Exeter and Hull University Hospital Foundation NHS Trusts and unrestricted educational grants from Biogen (Switzerland), Celltrion Healthcare (South Korea), Galapagos NV (Belgium), and F. Hoffmann-La Roche (Switzerland). The authors acknowledged numerous potential conflicts of interest, including receiving grants, personal fees, and nonfinancial support from various pharmaceutical companies.

Patients being treated with infliximab had weakened immune responses to the first dose of the ChAdOx1 nCoV-19 (Oxford/AstraZeneca) and BNT162b2 (Pfizer/BioNTech) vaccines, compared with patients on vedolizumab (Entyvio), although a very significant number of patients from both groups seroconverted after their second dose, according to a new U.K. study of patients with inflammatory bowel disease (IBD).

NoSystem images/Getty Images

“Antibody testing and adapted vaccine schedules should be considered to protect these at-risk patients,” Nicholas A. Kennedy, PhD, MBBS, of the University of Exeter (England) and colleagues wrote in a preprint published March 29 on MedRxiv.

Infliximab is an anti–tumor necrosis factor (anti-TNF) monoclonal antibody that’s approved to treat adult and pediatric Crohn’s disease and ulcerative colitis, as well as rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis, whereas vedolizumab, a gut selective anti-integrin alpha4beta7 monoclonal antibody that is not associated with impaired systemic immune responses, is approved to treat Crohn’s disease and ulcerative colitis in adults.

A previous study from Kennedy and colleagues revealed that IBD patients on infliximab showed a weakened COVID-19 antibody response compared with patients on vedolizumab. To determine if treatment with anti-TNF drugs impacted the efficacy of the first shot of these two-dose COVID-19 vaccines, the researchers used data from the CLARITY IBD study to assess 865 infliximab- and 428 vedolizumab-treated participants without evidence of prior SARS-CoV-2 infection who had received uninterrupted biologic therapy since being recruited between Sept. 22 and Dec. 23, 2020.

In the 3-10 weeks after initial vaccination, geometric mean concentrations for SARS-CoV-2 anti-spike protein receptor-binding protein antibodies were lower in patients on infliximab, compared with patients on vedolizumab for both the Pfizer (6.0 U/mL [5.9] versus 28.8 U/mL [5.4], P < .0001) and AstraZeneca (4.7 U/mL [4.9] versus 13.8 U/mL [5.9]; P < .0001) vaccines. The researchers’ multivariable models reinforced those findings, with antibody concentrations lower in infliximab-treated patients for both the Pfizer (fold change, 0.29; 95% confidence interval, 0.21-0.40; P < .0001) and AstraZeneca (FC, 0.39; 95% CI, 0.30-0.51; P < .0001) vaccines.

After second doses of the two-dose Pfizer vaccine, 85% of patients on infliximab and 86% of patients on vedolizumab seroconverted (P = .68); similarly high seroconversion rates were seen in patients who had been infected with SARS-CoV-2 prior to receiving either vaccine. Several patient characteristics were associated with lower antibody concentrations regardless of vaccine type: being 60 years or older, use of immunomodulators, having Crohn’s disease, and being a smoker. Alternatively, non-White ethnicity was associated with higher antibody concentrations.

Evidence has ‘unclear clinical significance’

“These data, which require peer review, do not change my opinion on the safety and efficacy of COVID-19 vaccines in patients taking TNF inhibitors such as infliximab as monotherapy for the treatment of psoriatic disease,” Joel M. Gelfand MD, director of the psoriasis and phototherapy treatment center at the University of Pennsylvania, Philadelphia, said in an interview.

Courtesy Dr. Joel M. Gelfand

“First, two peer-reviewed studies found good antibody response in patients on TNF inhibitors receiving COVID-19 vaccines (doi: 10.1136/annrheumdis-2021-220289; 10.1136/annrheumdis-2021-220272). Second, antibody responses were robust in the small cohort that received the second dose of a COVID-19 vaccine. We already know that, for the two messenger RNA-based vaccines available under emergency use authorization in the U.S., a second dose is required for optimal efficacy. Thus, evidence of a reduced antibody response after just one dose is of unclear clinical significance. Third, antibody responses are only a surrogate marker, and a low antibody response doesn’t necessarily mean the patient will not be protected by the vaccine.”
 

Focus on the second dose of a two-dose regimen

“Tell me about the response in people who got both doses of a vaccine that you’re supposed to get both doses of,” Jeffrey Curtis, MD, professor of medicine in the division of clinical immunology and rheumatology at the University of Alabama at Birmingham, said in an interview. “The number of patients in that subset was small [n = 27] but in my opinion that’s the most clinically relevant analysis and the one that patients and clinicians want answered.”

Courtesy UAB Photo

He also emphasized the uncertainty around what ‘protection’ means in these early days of studying COVID-19 vaccine responses. “You can define seroprotection or seroconversion as some absolute level of an antibody response, but if you want to say ‘Mrs. Smith, your antibody level was X,’ on whatever arbitrary scale with whoever’s arbitrary lab test, nobody actually knows that Mrs. Smith is now protected from SARS-CoV-2, or how protected,” he said.

“What is not terribly controversial is: If you can’t detect antibodies, the vaccine didn’t ‘take,’ if you will. But if I tell you that the mean antibody level was X with one drug and then 2X with another drug, does that mean that you’re twice as protected? We don’t know that. I’m fearful that people are looking at these studies and thinking that more is better. It might be, but we don’t know that to be true.”
 

Debating the cause of weakened immune responses

“The biological plausibility of being on an anti-TNF affecting your immune reaction to a messenger RNA or even a replication-deficient viral vector vaccine doesn’t make sense,” David T. Rubin, MD, professor of medicine at the University of Chicago and chair of the National Scientific Advisory Committee of the Crohn’s and Colitis Foundation, said in an interview.

“I’m sure immunologists may differ with me on this, but given what we have come to appreciate about these vaccine mechanisms, this finding doesn’t make intuitive sense. So we need to make sure that, when this happens, we look to the next studies and try to understand, was there any other confounder that may have resulted in these findings that was not adequately adjusted for or addressed in some other way?

“When you have a study of this size, you argue, ‘Because it’s so large, any effect that was seen must be real,’ ” he added. “Alternatively, to have a study of this size, by its very nature you are limited in being able to control for certain other factors or differences between the groups.”

That said, he commended the authors for their study and acknowledged the potential questions it raises about the single-shot Johnson & Johnson vaccine. “If you only get one and you’re on infliximab, this study implies that maybe that’s not enough,” he said. “Despite the fact that Johnson & Johnson was approved as a single dose, it may be necessary to think about it as the first of two, or maybe it’s not the preferred vaccine in this group of patients.”

The study was supported by the Royal Devon and Exeter and Hull University Hospital Foundation NHS Trusts and unrestricted educational grants from Biogen (Switzerland), Celltrion Healthcare (South Korea), Galapagos NV (Belgium), and F. Hoffmann-La Roche (Switzerland). The authors acknowledged numerous potential conflicts of interest, including receiving grants, personal fees, and nonfinancial support from various pharmaceutical companies.

Bimekizumab, an investigational humanized monoclonal antibody that inhibits both interleukin-17A and -17F, proved far more efficacious than adalimumab for treatment of moderate to severe plaque psoriasis in the head-to-head, phase 3 BE SURE trial, Jerry Bagel, MD, said at Innovations in Dermatology: Virtual Spring Conference 2021.

“Results demonstrated that bimekizumab was superior to adalimumab over 16 weeks of treatment in terms of the speed, depth, and durability of skin clearance,” reported Dr. Bagel, a dermatologist at the Psoriasis Center of Central New Jersey, East Windsor.

The Food and Drug Administration is now reviewing UCB’s application for marketing approval of bimekizumab for treatment of moderate to severe psoriasis in adults.

BE SURE was a 478-patient, double-blind, phase 3 trial in which patients were randomized to one of three regimens: 320 mg of bimekizumab every 4 weeks; the tumor necrosis factor blocker adalimumab (Humira) at 40 mg every 2 weeks for 24 weeks, followed by a switch to bimekizumab at 320 mg every 4 weeks; or 320 mg of bimekizumab every 4 weeks for 16 weeks, then ratcheting back to dosing every 8 weeks. The trial concluded at week 56, Dr. Bagel explained at the conference sponsored by MedscapeLIVE! and the producers of the Hawaii Dermatology Seminar and Caribbean Dermatology Symposium.

The two coprimary endpoints were the 16-week rates of a 90% improvement from baseline in Psoriasis Area and Severity Index score, or PASI 90 response, and an Investigator’s Global Assessment (IGA) score of 0 or 1, meaning clear or almost clear. Bimekizumab every 4 weeks bested adalimumab on both endpoints, with a PASI 90 rate of 86.2%, compared with 47.2%, and a IGA 0/1 rate of 85.3% versus 57.2%. The 16-week PASI 100 response rate was 60.8% with bimekizumab and 23.9% with adalimumab.

The response to bimekizumab was notably fast: already by week 4, the PASI 75 rate was 76.4%, compared with 31.4% with adalimumab. And once patients switched from adalimumab to bimekizumab at week 24, their response rates shot up rapidly. Bimekizumab was equally effective whether dosed at 320 mg every 4 weeks or at maintenance dosing every 8 weeks, such that at week 56 patients in all three study arms had PASI 90 rates of 82%-84%.

The most frequent treatment-emergent adverse events associated with bimekizumab were oral candidiasis, nasopharyngitis, and upper respiratory tract infection. The oral candidiasis, which occurred in 13.2% of patients on bimekizumab every 4 weeks, was mainly mild to moderate, localized, and in no instance led to discontinuation of therapy, according to Dr. Bagel.

“Very impressive data,” commented session comoderator Linda Stein Gold, MD. “This study shows some data that’s potentially unprecedented. Bimekizumab was superior to one of the drugs that we know, we’ve used, and know is very, very effective.”

“Note the speed of this drug,” added comoderator Bruce E. Strober, MD, PhD, of Yale University, New Haven, Conn., and Central Connecticut Dermatology, Cromwell, Conn. “It achieved at week 4 the efficacy that it took adalimumab until week 16 to reach. So it is a very fast drug. Bimekizumab will be the fastest drug you’ve ever, ever worked with.”

“You’ll see in the bimekizumab studies about a fivefold increased frequency of oral candidiasis relative to our more legacy IL-17 inhibitors, such as ixekizumab, secukinumab, and brodalumab. I think that means approximately one in five or one in six patients will have some form of candidiasis when you treat them with bimekizumab,” he said. Therefore, he added, “in some patients you’ll have to manage oral candidiasis. Most affected patients don’t leave the studies, so it’s manageable, but you’ll have to become something of an authority on how to treat with, for example, oral antifungal swish-and-swallow, swish-and-spit, or oral fluconazole. And some of these patients will have recurrent infections.”

It’s a prospect that doesn’t concern Dr. Stein Gold. “This is a side effect that we can treat. We can see it, we’re comfortable with it, and it’s certainly something we can get a handle on,” said Dr. Stein Gold, director of dermatology clinical research at the Henry Ford Health System in Detroit.

BE SURE was funded by UCB. Dr. Bagel reported serving as a speaker for, consultant to, and paid investigator for AbbVie, Celgene, Eli Lilly, Leo Pharma, Novartis, and Ortho Pharmaceuticals. Dr. Stein Gold and Dr. Strober reported having financial relationships with numerous pharmaceutical companies.

MedscapeLIVE! and this news organization are owned by the same parent company.

bjancin@mdedge.com

Bimekizumab, an investigational humanized monoclonal antibody that inhibits both interleukin-17A and -17F, proved far more efficacious than adalimumab for treatment of moderate to severe plaque psoriasis in the head-to-head, phase 3 BE SURE trial, Jerry Bagel, MD, said at Innovations in Dermatology: Virtual Spring Conference 2021.

“Results demonstrated that bimekizumab was superior to adalimumab over 16 weeks of treatment in terms of the speed, depth, and durability of skin clearance,” reported Dr. Bagel, a dermatologist at the Psoriasis Center of Central New Jersey, East Windsor.

The Food and Drug Administration is now reviewing UCB’s application for marketing approval of bimekizumab for treatment of moderate to severe psoriasis in adults.

BE SURE was a 478-patient, double-blind, phase 3 trial in which patients were randomized to one of three regimens: 320 mg of bimekizumab every 4 weeks; the tumor necrosis factor blocker adalimumab (Humira) at 40 mg every 2 weeks for 24 weeks, followed by a switch to bimekizumab at 320 mg every 4 weeks; or 320 mg of bimekizumab every 4 weeks for 16 weeks, then ratcheting back to dosing every 8 weeks. The trial concluded at week 56, Dr. Bagel explained at the conference sponsored by MedscapeLIVE! and the producers of the Hawaii Dermatology Seminar and Caribbean Dermatology Symposium.

The two coprimary endpoints were the 16-week rates of a 90% improvement from baseline in Psoriasis Area and Severity Index score, or PASI 90 response, and an Investigator’s Global Assessment (IGA) score of 0 or 1, meaning clear or almost clear. Bimekizumab every 4 weeks bested adalimumab on both endpoints, with a PASI 90 rate of 86.2%, compared with 47.2%, and a IGA 0/1 rate of 85.3% versus 57.2%. The 16-week PASI 100 response rate was 60.8% with bimekizumab and 23.9% with adalimumab.

The response to bimekizumab was notably fast: already by week 4, the PASI 75 rate was 76.4%, compared with 31.4% with adalimumab. And once patients switched from adalimumab to bimekizumab at week 24, their response rates shot up rapidly. Bimekizumab was equally effective whether dosed at 320 mg every 4 weeks or at maintenance dosing every 8 weeks, such that at week 56 patients in all three study arms had PASI 90 rates of 82%-84%.

The most frequent treatment-emergent adverse events associated with bimekizumab were oral candidiasis, nasopharyngitis, and upper respiratory tract infection. The oral candidiasis, which occurred in 13.2% of patients on bimekizumab every 4 weeks, was mainly mild to moderate, localized, and in no instance led to discontinuation of therapy, according to Dr. Bagel.

“Very impressive data,” commented session comoderator Linda Stein Gold, MD. “This study shows some data that’s potentially unprecedented. Bimekizumab was superior to one of the drugs that we know, we’ve used, and know is very, very effective.”

“Note the speed of this drug,” added comoderator Bruce E. Strober, MD, PhD, of Yale University, New Haven, Conn., and Central Connecticut Dermatology, Cromwell, Conn. “It achieved at week 4 the efficacy that it took adalimumab until week 16 to reach. So it is a very fast drug. Bimekizumab will be the fastest drug you’ve ever, ever worked with.”

“You’ll see in the bimekizumab studies about a fivefold increased frequency of oral candidiasis relative to our more legacy IL-17 inhibitors, such as ixekizumab, secukinumab, and brodalumab. I think that means approximately one in five or one in six patients will have some form of candidiasis when you treat them with bimekizumab,” he said. Therefore, he added, “in some patients you’ll have to manage oral candidiasis. Most affected patients don’t leave the studies, so it’s manageable, but you’ll have to become something of an authority on how to treat with, for example, oral antifungal swish-and-swallow, swish-and-spit, or oral fluconazole. And some of these patients will have recurrent infections.”

It’s a prospect that doesn’t concern Dr. Stein Gold. “This is a side effect that we can treat. We can see it, we’re comfortable with it, and it’s certainly something we can get a handle on,” said Dr. Stein Gold, director of dermatology clinical research at the Henry Ford Health System in Detroit.

BE SURE was funded by UCB. Dr. Bagel reported serving as a speaker for, consultant to, and paid investigator for AbbVie, Celgene, Eli Lilly, Leo Pharma, Novartis, and Ortho Pharmaceuticals. Dr. Stein Gold and Dr. Strober reported having financial relationships with numerous pharmaceutical companies.

MedscapeLIVE! and this news organization are owned by the same parent company.

bjancin@mdedge.com

Bimekizumab, an investigational humanized monoclonal antibody that inhibits both interleukin-17A and -17F, proved far more efficacious than adalimumab for treatment of moderate to severe plaque psoriasis in the head-to-head, phase 3 BE SURE trial, Jerry Bagel, MD, said at Innovations in Dermatology: Virtual Spring Conference 2021.

“Results demonstrated that bimekizumab was superior to adalimumab over 16 weeks of treatment in terms of the speed, depth, and durability of skin clearance,” reported Dr. Bagel, a dermatologist at the Psoriasis Center of Central New Jersey, East Windsor.

The Food and Drug Administration is now reviewing UCB’s application for marketing approval of bimekizumab for treatment of moderate to severe psoriasis in adults.

BE SURE was a 478-patient, double-blind, phase 3 trial in which patients were randomized to one of three regimens: 320 mg of bimekizumab every 4 weeks; the tumor necrosis factor blocker adalimumab (Humira) at 40 mg every 2 weeks for 24 weeks, followed by a switch to bimekizumab at 320 mg every 4 weeks; or 320 mg of bimekizumab every 4 weeks for 16 weeks, then ratcheting back to dosing every 8 weeks. The trial concluded at week 56, Dr. Bagel explained at the conference sponsored by MedscapeLIVE! and the producers of the Hawaii Dermatology Seminar and Caribbean Dermatology Symposium.

The two coprimary endpoints were the 16-week rates of a 90% improvement from baseline in Psoriasis Area and Severity Index score, or PASI 90 response, and an Investigator’s Global Assessment (IGA) score of 0 or 1, meaning clear or almost clear. Bimekizumab every 4 weeks bested adalimumab on both endpoints, with a PASI 90 rate of 86.2%, compared with 47.2%, and a IGA 0/1 rate of 85.3% versus 57.2%. The 16-week PASI 100 response rate was 60.8% with bimekizumab and 23.9% with adalimumab.

The response to bimekizumab was notably fast: already by week 4, the PASI 75 rate was 76.4%, compared with 31.4% with adalimumab. And once patients switched from adalimumab to bimekizumab at week 24, their response rates shot up rapidly. Bimekizumab was equally effective whether dosed at 320 mg every 4 weeks or at maintenance dosing every 8 weeks, such that at week 56 patients in all three study arms had PASI 90 rates of 82%-84%.

The most frequent treatment-emergent adverse events associated with bimekizumab were oral candidiasis, nasopharyngitis, and upper respiratory tract infection. The oral candidiasis, which occurred in 13.2% of patients on bimekizumab every 4 weeks, was mainly mild to moderate, localized, and in no instance led to discontinuation of therapy, according to Dr. Bagel.

“Very impressive data,” commented session comoderator Linda Stein Gold, MD. “This study shows some data that’s potentially unprecedented. Bimekizumab was superior to one of the drugs that we know, we’ve used, and know is very, very effective.”

“Note the speed of this drug,” added comoderator Bruce E. Strober, MD, PhD, of Yale University, New Haven, Conn., and Central Connecticut Dermatology, Cromwell, Conn. “It achieved at week 4 the efficacy that it took adalimumab until week 16 to reach. So it is a very fast drug. Bimekizumab will be the fastest drug you’ve ever, ever worked with.”

“You’ll see in the bimekizumab studies about a fivefold increased frequency of oral candidiasis relative to our more legacy IL-17 inhibitors, such as ixekizumab, secukinumab, and brodalumab. I think that means approximately one in five or one in six patients will have some form of candidiasis when you treat them with bimekizumab,” he said. Therefore, he added, “in some patients you’ll have to manage oral candidiasis. Most affected patients don’t leave the studies, so it’s manageable, but you’ll have to become something of an authority on how to treat with, for example, oral antifungal swish-and-swallow, swish-and-spit, or oral fluconazole. And some of these patients will have recurrent infections.”

It’s a prospect that doesn’t concern Dr. Stein Gold. “This is a side effect that we can treat. We can see it, we’re comfortable with it, and it’s certainly something we can get a handle on,” said Dr. Stein Gold, director of dermatology clinical research at the Henry Ford Health System in Detroit.

BE SURE was funded by UCB. Dr. Bagel reported serving as a speaker for, consultant to, and paid investigator for AbbVie, Celgene, Eli Lilly, Leo Pharma, Novartis, and Ortho Pharmaceuticals. Dr. Stein Gold and Dr. Strober reported having financial relationships with numerous pharmaceutical companies.

MedscapeLIVE! and this news organization are owned by the same parent company.

bjancin@mdedge.com

The National Psoriasis Foundation COVID-19 Task Force now recommends that certain patients on methotrexate consider stopping the drug for 2 weeks after receiving the Johnson & Johnson COVID-19 vaccine, Joel M. Gelfand, MD, said at Innovations in Dermatology: Virtual Spring Conference 2021.

Courtesy Dr. Joel M. Gelfand

The new guidance states: “Patients 60 or older who have at least one comorbidity associated with an increased risk for poor COVID-19 outcomes, and who are taking methotrexate with well-controlled psoriatic disease, may, in consultation with their prescriber, consider holding it for 2 weeks after receiving the Ad26.COV2.S [Johnson & Johnson] vaccine in order to potentially improve vaccine response.”

The key word here is “potentially.” There is no hard evidence that a 2-week hold on methotrexate after receiving the killed adenovirus vaccine will actually provide a clinically meaningful benefit. But it’s a hypothetical possibility. The rationale stems from a small randomized trial conducted in South Korea several years ago in which patients with rheumatoid arthritis were assigned to hold or continue their methotrexate for the first 2 weeks after receiving an inactivated-virus influenza vaccine. The antibody response to the vaccine was better in those who temporarily halted their methotrexate, explained Dr. Gelfand, cochair of the NPF COVID-19 Task Force and professor of dermatology and of epidemiology at the University of Pennsylvania, Philadelphia.

“If you have a patient on methotrexate who’s 60 or older and whose psoriasis is completely controlled and quiescent and the patient is concerned about how well the vaccine is going to work, this is a reasonable thing to consider in someone who’s at higher risk for poor outcomes if they get infected,” he said.

If the informed patient wants to continue on methotrexate without interruption, that’s fine, too, in light of the lack of compelling evidence on this issue, the dermatologist added at the conference, sponsored by MedscapeLIVE! and the producers of the Hawaii Dermatology Seminar and Caribbean Dermatology Symposium.

The NPF task force does not extend the recommendation to consider holding methotrexate in recipients of the mRNA-based Moderna and Pfizer vaccines because of their very different mechanisms of action. Nor is it recommended to hold biologic agents after receiving any of the available COVID-19 vaccines. Studies have shown no altered immunologic response to influenza or pneumococcal vaccines in patients who continued on tumor necrosis factor inhibitors or interleukin-17 inhibitors. The interleukin-23 inhibitors haven’t been studied in this regard.

The task force recommends that most psoriasis patients should continue on treatment throughout the pandemic, and newly diagnosed patients should commence appropriate therapy as if there was no pandemic.

“We’ve learned that many patients who stopped their treatment for psoriatic disease early in the pandemic came to regret that decision because their psoriasis flared and got worse and required reinstitution of therapy,” Dr. Gelfand said. “The current data is largely reassuring that if there is an effect of our therapies on the risk of COVID, it must be rather small and therefore unlikely to be clinically meaningful for our patients.”

Dr. Gelfand reported serving as a consultant to and recipient of institutional research grants from Pfizer and numerous other pharmaceutical companies.

MedscapeLIVE and this news organization are owned by the same parent company.

bjancin@mdedge.com

The National Psoriasis Foundation COVID-19 Task Force now recommends that certain patients on methotrexate consider stopping the drug for 2 weeks after receiving the Johnson & Johnson COVID-19 vaccine, Joel M. Gelfand, MD, said at Innovations in Dermatology: Virtual Spring Conference 2021.

Courtesy Dr. Joel M. Gelfand

The new guidance states: “Patients 60 or older who have at least one comorbidity associated with an increased risk for poor COVID-19 outcomes, and who are taking methotrexate with well-controlled psoriatic disease, may, in consultation with their prescriber, consider holding it for 2 weeks after receiving the Ad26.COV2.S [Johnson & Johnson] vaccine in order to potentially improve vaccine response.”

The key word here is “potentially.” There is no hard evidence that a 2-week hold on methotrexate after receiving the killed adenovirus vaccine will actually provide a clinically meaningful benefit. But it’s a hypothetical possibility. The rationale stems from a small randomized trial conducted in South Korea several years ago in which patients with rheumatoid arthritis were assigned to hold or continue their methotrexate for the first 2 weeks after receiving an inactivated-virus influenza vaccine. The antibody response to the vaccine was better in those who temporarily halted their methotrexate, explained Dr. Gelfand, cochair of the NPF COVID-19 Task Force and professor of dermatology and of epidemiology at the University of Pennsylvania, Philadelphia.

“If you have a patient on methotrexate who’s 60 or older and whose psoriasis is completely controlled and quiescent and the patient is concerned about how well the vaccine is going to work, this is a reasonable thing to consider in someone who’s at higher risk for poor outcomes if they get infected,” he said.

If the informed patient wants to continue on methotrexate without interruption, that’s fine, too, in light of the lack of compelling evidence on this issue, the dermatologist added at the conference, sponsored by MedscapeLIVE! and the producers of the Hawaii Dermatology Seminar and Caribbean Dermatology Symposium.

The NPF task force does not extend the recommendation to consider holding methotrexate in recipients of the mRNA-based Moderna and Pfizer vaccines because of their very different mechanisms of action. Nor is it recommended to hold biologic agents after receiving any of the available COVID-19 vaccines. Studies have shown no altered immunologic response to influenza or pneumococcal vaccines in patients who continued on tumor necrosis factor inhibitors or interleukin-17 inhibitors. The interleukin-23 inhibitors haven’t been studied in this regard.

The task force recommends that most psoriasis patients should continue on treatment throughout the pandemic, and newly diagnosed patients should commence appropriate therapy as if there was no pandemic.

“We’ve learned that many patients who stopped their treatment for psoriatic disease early in the pandemic came to regret that decision because their psoriasis flared and got worse and required reinstitution of therapy,” Dr. Gelfand said. “The current data is largely reassuring that if there is an effect of our therapies on the risk of COVID, it must be rather small and therefore unlikely to be clinically meaningful for our patients.”

Dr. Gelfand reported serving as a consultant to and recipient of institutional research grants from Pfizer and numerous other pharmaceutical companies.

MedscapeLIVE and this news organization are owned by the same parent company.

bjancin@mdedge.com

The National Psoriasis Foundation COVID-19 Task Force now recommends that certain patients on methotrexate consider stopping the drug for 2 weeks after receiving the Johnson & Johnson COVID-19 vaccine, Joel M. Gelfand, MD, said at Innovations in Dermatology: Virtual Spring Conference 2021.

Courtesy Dr. Joel M. Gelfand

The new guidance states: “Patients 60 or older who have at least one comorbidity associated with an increased risk for poor COVID-19 outcomes, and who are taking methotrexate with well-controlled psoriatic disease, may, in consultation with their prescriber, consider holding it for 2 weeks after receiving the Ad26.COV2.S [Johnson & Johnson] vaccine in order to potentially improve vaccine response.”

The key word here is “potentially.” There is no hard evidence that a 2-week hold on methotrexate after receiving the killed adenovirus vaccine will actually provide a clinically meaningful benefit. But it’s a hypothetical possibility. The rationale stems from a small randomized trial conducted in South Korea several years ago in which patients with rheumatoid arthritis were assigned to hold or continue their methotrexate for the first 2 weeks after receiving an inactivated-virus influenza vaccine. The antibody response to the vaccine was better in those who temporarily halted their methotrexate, explained Dr. Gelfand, cochair of the NPF COVID-19 Task Force and professor of dermatology and of epidemiology at the University of Pennsylvania, Philadelphia.

“If you have a patient on methotrexate who’s 60 or older and whose psoriasis is completely controlled and quiescent and the patient is concerned about how well the vaccine is going to work, this is a reasonable thing to consider in someone who’s at higher risk for poor outcomes if they get infected,” he said.

If the informed patient wants to continue on methotrexate without interruption, that’s fine, too, in light of the lack of compelling evidence on this issue, the dermatologist added at the conference, sponsored by MedscapeLIVE! and the producers of the Hawaii Dermatology Seminar and Caribbean Dermatology Symposium.

The NPF task force does not extend the recommendation to consider holding methotrexate in recipients of the mRNA-based Moderna and Pfizer vaccines because of their very different mechanisms of action. Nor is it recommended to hold biologic agents after receiving any of the available COVID-19 vaccines. Studies have shown no altered immunologic response to influenza or pneumococcal vaccines in patients who continued on tumor necrosis factor inhibitors or interleukin-17 inhibitors. The interleukin-23 inhibitors haven’t been studied in this regard.

The task force recommends that most psoriasis patients should continue on treatment throughout the pandemic, and newly diagnosed patients should commence appropriate therapy as if there was no pandemic.

“We’ve learned that many patients who stopped their treatment for psoriatic disease early in the pandemic came to regret that decision because their psoriasis flared and got worse and required reinstitution of therapy,” Dr. Gelfand said. “The current data is largely reassuring that if there is an effect of our therapies on the risk of COVID, it must be rather small and therefore unlikely to be clinically meaningful for our patients.”

Dr. Gelfand reported serving as a consultant to and recipient of institutional research grants from Pfizer and numerous other pharmaceutical companies.

MedscapeLIVE and this news organization are owned by the same parent company.

bjancin@mdedge.com

Long-term proactive topical management of plaque psoriasis with twice-weekly calcipotriene/betamethasone dipropionate foam has been shown in a high-quality randomized trial to be more effective than conventional reactive management – but will patients go for it?

Bruce E. Strober, MD, PhD, has his doubts, and he shared them with Linda Stein Gold, MD, after she presented updated results from the 52-week PSO-LONG trial at Innovations in Dermatology: Virtual Spring Conference 2021.

In order for the proactive management approach tested in this study to be successful, patients must apply the topical agent as maintenance therapy to cleared areas where they previously had psoriasis. And while they did so in this study with an assist in the form of monthly office visits and nudging from investigators, in real-world clinical practice that’s unlikely to happen, according to Dr. Strober, of Yale University, New Haven, Conn.

“It makes sense to do what’s being done in this study, there’s no doubt, but I’m concerned about adherence and whether patients are really going to do it,” he said.

“Adherence is going to be everything here, and you know patients don’t like to apply topicals to their body. Once they’re clear they’re just going to walk away from the topical,” Dr. Strober predicted.

Dr. Stein Gold countered: “When a study goes on for a full year, it starts to reflect real life.”

Moreover, the PSO-LONG trial provides the first high-quality evidence physicians can share with patients demonstrating that proactive management pays off in terms of fewer relapses and more time in remission over the long haul, added Dr. Stein Gold, director of dermatology clinical research at the Henry Ford Health System in Detroit.

PSO-LONG was a double-blind, international, phase 3 study including 545 adults with plaque psoriasis who had clear or almost-clear skin after 4 weeks of once-daily calcipotriene 0.005%/betamethasone dipropionate 0.064% (Cal/BD) foam (Enstilar), and were then randomized to twice-weekly proactive management or to a reactive approach involving application of vehicle on the same twice-weekly schedule. Relapses resulted in rescue therapy with 4 weeks of once-daily Cal/BD foam.

The primary endpoint was the median time to first relapse: 56 days with the proactive approach, a significant improvement over the 30 days with the reactive approach. Over the course of 52 weeks, the proactive group spent an additional 41 days in remission, compared with the reactive group. Patients randomized to twice-weekly Cal/BD foam averaged 3.1 relapses per year, compared with 4.8 with reactive management. The side-effect profiles in the two study arms were similar.

Mean Physician Global Assessment scores and Psoriasis Area and Activity Index scores for the proactive group clearly separated from the reactive group by week 4, with those differences maintained throughout the year. The area under the curve for distribution for the Physician Global Assessment score was 15% lower in the proactive group, and 20% lower for the modified PASI score.

“These results suggest that proactive management – a concept that’s been used for atopic dermatitis – could be applied to patients with psoriasis to prolong remission,” Dr. Stein Gold concluded at the conference, sponsored by MedscapeLIVE! and the producers of the Hawaii Dermatology Seminar and Caribbean Dermatology Symposium.

Asked how confident she is that patients in the real world truly will do this, Dr. Stein Gold replied: “You know, I don’t know. We hope so. Now we can tell them we actually have some data that supports treating the cleared areas. And it’s only twice a week, separated on Mondays and Thursdays.”

“I take a much more reactive approach,” Dr. Strober said. “I advise patients to get back in there with their topical steroid as soon as they see any signs of recurrence.

He added that he’s eager to see if a proactive management approach such as the one that was successful in PSO-LONG is also beneficial using some of the promising topical agents with nonsteroidal mechanisms of action, which are advancing through the developmental pipeline.

Late in 2020, the Food and Drug Administration approved an expanded indication for Cal/BD foam, which includes the PSO-LONG data on the efficacy and safety of long-term twice-weekly therapy in adults in product labeling. The combination spray/foam was previously approved by the FDA as once-daily therapy in psoriasis patients aged 12 years and older, but only for up to 4 weeks because of safety concerns regarding longer use of the potent topical steroid as daily therapy.

The PSO-LONG trial was funded by LEO Pharma. Dr. Stein Gold reported serving as a paid investigator and/or consultant to LEO and numerous other pharmaceutical companies. Dr. Strober, reported serving as a consultant to more than two dozen pharmaceutical companies. MedscapeLIVE! and this news organization are owned by the same parent company.

bjancin@mdedge.com

Long-term proactive topical management of plaque psoriasis with twice-weekly calcipotriene/betamethasone dipropionate foam has been shown in a high-quality randomized trial to be more effective than conventional reactive management – but will patients go for it?

Bruce E. Strober, MD, PhD, has his doubts, and he shared them with Linda Stein Gold, MD, after she presented updated results from the 52-week PSO-LONG trial at Innovations in Dermatology: Virtual Spring Conference 2021.

In order for the proactive management approach tested in this study to be successful, patients must apply the topical agent as maintenance therapy to cleared areas where they previously had psoriasis. And while they did so in this study with an assist in the form of monthly office visits and nudging from investigators, in real-world clinical practice that’s unlikely to happen, according to Dr. Strober, of Yale University, New Haven, Conn.

“It makes sense to do what’s being done in this study, there’s no doubt, but I’m concerned about adherence and whether patients are really going to do it,” he said.

“Adherence is going to be everything here, and you know patients don’t like to apply topicals to their body. Once they’re clear they’re just going to walk away from the topical,” Dr. Strober predicted.

Dr. Stein Gold countered: “When a study goes on for a full year, it starts to reflect real life.”

Moreover, the PSO-LONG trial provides the first high-quality evidence physicians can share with patients demonstrating that proactive management pays off in terms of fewer relapses and more time in remission over the long haul, added Dr. Stein Gold, director of dermatology clinical research at the Henry Ford Health System in Detroit.

PSO-LONG was a double-blind, international, phase 3 study including 545 adults with plaque psoriasis who had clear or almost-clear skin after 4 weeks of once-daily calcipotriene 0.005%/betamethasone dipropionate 0.064% (Cal/BD) foam (Enstilar), and were then randomized to twice-weekly proactive management or to a reactive approach involving application of vehicle on the same twice-weekly schedule. Relapses resulted in rescue therapy with 4 weeks of once-daily Cal/BD foam.

The primary endpoint was the median time to first relapse: 56 days with the proactive approach, a significant improvement over the 30 days with the reactive approach. Over the course of 52 weeks, the proactive group spent an additional 41 days in remission, compared with the reactive group. Patients randomized to twice-weekly Cal/BD foam averaged 3.1 relapses per year, compared with 4.8 with reactive management. The side-effect profiles in the two study arms were similar.

Mean Physician Global Assessment scores and Psoriasis Area and Activity Index scores for the proactive group clearly separated from the reactive group by week 4, with those differences maintained throughout the year. The area under the curve for distribution for the Physician Global Assessment score was 15% lower in the proactive group, and 20% lower for the modified PASI score.

“These results suggest that proactive management – a concept that’s been used for atopic dermatitis – could be applied to patients with psoriasis to prolong remission,” Dr. Stein Gold concluded at the conference, sponsored by MedscapeLIVE! and the producers of the Hawaii Dermatology Seminar and Caribbean Dermatology Symposium.

Asked how confident she is that patients in the real world truly will do this, Dr. Stein Gold replied: “You know, I don’t know. We hope so. Now we can tell them we actually have some data that supports treating the cleared areas. And it’s only twice a week, separated on Mondays and Thursdays.”

“I take a much more reactive approach,” Dr. Strober said. “I advise patients to get back in there with their topical steroid as soon as they see any signs of recurrence.

He added that he’s eager to see if a proactive management approach such as the one that was successful in PSO-LONG is also beneficial using some of the promising topical agents with nonsteroidal mechanisms of action, which are advancing through the developmental pipeline.

Late in 2020, the Food and Drug Administration approved an expanded indication for Cal/BD foam, which includes the PSO-LONG data on the efficacy and safety of long-term twice-weekly therapy in adults in product labeling. The combination spray/foam was previously approved by the FDA as once-daily therapy in psoriasis patients aged 12 years and older, but only for up to 4 weeks because of safety concerns regarding longer use of the potent topical steroid as daily therapy.

The PSO-LONG trial was funded by LEO Pharma. Dr. Stein Gold reported serving as a paid investigator and/or consultant to LEO and numerous other pharmaceutical companies. Dr. Strober, reported serving as a consultant to more than two dozen pharmaceutical companies. MedscapeLIVE! and this news organization are owned by the same parent company.

bjancin@mdedge.com

Long-term proactive topical management of plaque psoriasis with twice-weekly calcipotriene/betamethasone dipropionate foam has been shown in a high-quality randomized trial to be more effective than conventional reactive management – but will patients go for it?

Bruce E. Strober, MD, PhD, has his doubts, and he shared them with Linda Stein Gold, MD, after she presented updated results from the 52-week PSO-LONG trial at Innovations in Dermatology: Virtual Spring Conference 2021.

In order for the proactive management approach tested in this study to be successful, patients must apply the topical agent as maintenance therapy to cleared areas where they previously had psoriasis. And while they did so in this study with an assist in the form of monthly office visits and nudging from investigators, in real-world clinical practice that’s unlikely to happen, according to Dr. Strober, of Yale University, New Haven, Conn.

“It makes sense to do what’s being done in this study, there’s no doubt, but I’m concerned about adherence and whether patients are really going to do it,” he said.

“Adherence is going to be everything here, and you know patients don’t like to apply topicals to their body. Once they’re clear they’re just going to walk away from the topical,” Dr. Strober predicted.

Dr. Stein Gold countered: “When a study goes on for a full year, it starts to reflect real life.”

Moreover, the PSO-LONG trial provides the first high-quality evidence physicians can share with patients demonstrating that proactive management pays off in terms of fewer relapses and more time in remission over the long haul, added Dr. Stein Gold, director of dermatology clinical research at the Henry Ford Health System in Detroit.

PSO-LONG was a double-blind, international, phase 3 study including 545 adults with plaque psoriasis who had clear or almost-clear skin after 4 weeks of once-daily calcipotriene 0.005%/betamethasone dipropionate 0.064% (Cal/BD) foam (Enstilar), and were then randomized to twice-weekly proactive management or to a reactive approach involving application of vehicle on the same twice-weekly schedule. Relapses resulted in rescue therapy with 4 weeks of once-daily Cal/BD foam.

The primary endpoint was the median time to first relapse: 56 days with the proactive approach, a significant improvement over the 30 days with the reactive approach. Over the course of 52 weeks, the proactive group spent an additional 41 days in remission, compared with the reactive group. Patients randomized to twice-weekly Cal/BD foam averaged 3.1 relapses per year, compared with 4.8 with reactive management. The side-effect profiles in the two study arms were similar.

Mean Physician Global Assessment scores and Psoriasis Area and Activity Index scores for the proactive group clearly separated from the reactive group by week 4, with those differences maintained throughout the year. The area under the curve for distribution for the Physician Global Assessment score was 15% lower in the proactive group, and 20% lower for the modified PASI score.

“These results suggest that proactive management – a concept that’s been used for atopic dermatitis – could be applied to patients with psoriasis to prolong remission,” Dr. Stein Gold concluded at the conference, sponsored by MedscapeLIVE! and the producers of the Hawaii Dermatology Seminar and Caribbean Dermatology Symposium.

Asked how confident she is that patients in the real world truly will do this, Dr. Stein Gold replied: “You know, I don’t know. We hope so. Now we can tell them we actually have some data that supports treating the cleared areas. And it’s only twice a week, separated on Mondays and Thursdays.”

“I take a much more reactive approach,” Dr. Strober said. “I advise patients to get back in there with their topical steroid as soon as they see any signs of recurrence.

He added that he’s eager to see if a proactive management approach such as the one that was successful in PSO-LONG is also beneficial using some of the promising topical agents with nonsteroidal mechanisms of action, which are advancing through the developmental pipeline.

Late in 2020, the Food and Drug Administration approved an expanded indication for Cal/BD foam, which includes the PSO-LONG data on the efficacy and safety of long-term twice-weekly therapy in adults in product labeling. The combination spray/foam was previously approved by the FDA as once-daily therapy in psoriasis patients aged 12 years and older, but only for up to 4 weeks because of safety concerns regarding longer use of the potent topical steroid as daily therapy.

The PSO-LONG trial was funded by LEO Pharma. Dr. Stein Gold reported serving as a paid investigator and/or consultant to LEO and numerous other pharmaceutical companies. Dr. Strober, reported serving as a consultant to more than two dozen pharmaceutical companies. MedscapeLIVE! and this news organization are owned by the same parent company.

bjancin@mdedge.com

Generalized pustular psoriasis of pregnancy (GPPP), formerly known as impetigo herpetiformis, is a rare dermatosis that causes maternal and fetal morbidity and mortality. It is characterized by widespread, circular, erythematous plaques with pustules at the periphery.¹ Conventional first-line treatment includes systemic corticosteroids and cyclosporine. The National Psoriasis Foundation Medical Board also has included infliximab among the first-line treatment options for GPPP.² Herein, we report a case of GPPP treated with infliximab at 30 weeks’ gestation and during the postpartum period.

Case Report

A 22-year-old woman was admitted to our inpatient clinic at 20 weeks’ gestation in her second pregnancy for evaluation of cutaneous eruptions covering the entire body. The lesions first appeared 3 to 4 days prior to her admission and dramatically progressed. She had a history of psoriasis vulgaris diagnosed during her first pregnancy 2 years prior that was treated with topical steroids throughout the pregnancy and methotrexate during lactation for a total of 11 months. She then was started on cyclosporine, which she used for 6 months due to ineffectiveness of the methotrexate, but she stopped treatment 4 months before the second pregnancy.

At the current presentation, physical examination revealed erythroderma and widespread pustules on the chest, abdomen, arms, and legs, including the intertriginous regions, that tended to coalesce and form lakes of pus over an erythematous base (Figure 1). The mucosae were normal. She exhibited a low blood pressure (85/50 mmHg) and high body temperature (102 °F [38.9 °C]). Routine laboratory examination revealed anemia and a normal leukocyte count. Her erythrocyte sedimentation rate (57 mm/h [reference range, <20 mm/h]) and C-reactive protein level (102 mg/L [reference range, <6 mg/L]) were elevated, whereas total calcium (8.11 mg/dL [reference range, 8.2–10.6 mg/dL]) and albumin (3.15 g/dL [reference range, >4.0 g/dL]) levels were low.

The patient returned to the clinic 3 weeks postpartum with a few pustules on erythematous plaques on the chest, abdomen, and back. At this time, she received a third infusion of infliximab 8 weeks after the second dose. For the past 5 years, the patient has been undergoing infliximab maintenance treatment, which she receives at the hospital every 8 weeks with excellent response. She has had no further pregnancies to date.

Comment

Generalized pustular psoriasis of pregnancy is a rare condition that typically occurs in the third trimester but also can start in the first and second trimesters. It may result in maternal and fetal morbidity by causing fluid and electrolyte imbalance and/or placental insufficiency, resulting in an increased risk for fetal abnormalities, stillbirth, and neonatal death.³ In subsequent pregnancies, GPPP has been observed to recur at an earlier gestational age with a more severe presentation.^1,3

Generalized pustular psoriasis of pregnancy usually involves an eruption that begins symmetrically in the intertriginous areas and spreads to the rest of the body. The lesions present as erythematous annular plaques with pustules on the periphery and desquamation in the center due to older pustules.^1,3 The mucous membranes also may be involved with erosive and exfoliative plaques, and there may be nail involvement. Patients often present with systemic symptoms such as fever, malaise, diarrhea, and vomiting.¹ Laboratory investigations may reveal neutrophilic leukocytosis, high erythrocyte sedimentation rate, hypocalcemia, and hypoalbuminemia.⁴ Cultures from blood and pustules show no bacterial growth. A skin biopsy is helpful in diagnosis, with features similar to generalized pustular psoriasis, demonstrating spongiform pustules containing neutrophils, lymphocytic and neutrophilic infiltrates in the papillary dermis, and negative direct immunofluorescence.³

The differential diagnosis of GPPP includes subcorneal pustular dermatosis, dermatitis herpetiformis, herpes gestationis, impetigo, and acute generalized exanthematous pustulosis.^1,3 Due to concerns of fetal implications, treatment options in GPPP are somewhat limited; however, the condition requires treatment because it may result in unfavorable pregnancy outcomes. Topical corticosteroids may be an option for limited disease.^5,6 Systemic corticosteroids (eg, prednisone 60–80 mg/d) were previously considered as first-line agents, although they have shown limited efficacy in our case as well as in other case reports.⁷ Their ineffectiveness and risk for flare-up after dose tapering should be kept in mind when starting GPPP patients on systemic corticosteroids. Systemic cyclosporine (2–3 mg/kg/d) may be added to increase the efficacy of systemic steroids, which was done in several cases in literature.^1,6,8 Although cyclosporine has been classified as a pregnancy category C drug, an analysis of pregnancy outcomes of 629 renal transplant patients revealed no association with adverse pregnancy outcomes compared to the general population and no increase in fetal malformations.⁹ Therefore, cyclosporine is a safe treatment option and was classified as a first-line drug for GPPP in a 2012 review by the National Psoriasis Foundation Medical Board.² Narrowband UVB also has been reported to be used for the treatment of GPPP.¹⁰ Methotrexate and retinoids have been used in cases with lesions that persisted postpartum.¹

Anti–tumor necrosis factor (TNF) α agents are another effective option for treatment of GPPP. Anti-TNF agents are classified as pregnancy category B due to results showing that anti-mouse TNF-α monoclonal antibodies did not cause embryotoxicity or teratogenicity in pregnant mice.¹¹ Although Carter et al¹² published a review of US Food and Drug Administration data on pregnant women receiving anti-TNF treatment and concluded that these agents were associated with the VACTERL group of malformations (vertebral defects, anal atresia, cardiac defect, tracheoesophageal fistula with esophageal atresia, cardiac defects, renal and limb anomalies), no such association was found in further studies. A 2014 study showed no difference in the rate of major malformations in infants born to women who were treated with anti-TNF drugs compared to the disease-matched group not treated with these agents and pregnant women counselled for nonteratogenic exposure.¹³ The same study detected an increase in preterm and low-birth-weight deliveries and suggested this might be caused by the increased severity of disease in patients requiring anti-TNF medication. The British Society of Rheumatology Biologics Register published data on pregnancy outcomes in 130 rheumatoid arthritis patients who had been exposed to anti-TNF agents.¹⁴ The results suggested an increased rate of spontaneous abortions in women exposed to anti-TNF treatment around the time of conception, especially in those taking these medications together with methotrexate or leflunomide; however, results also indicated that disease activity may have had an impact on the rate of spontaneous abortions in these patients. In a 2013 review of 462 women with inflammatory bowel disease who had been exposed to anti-TNF agents during pregnancy, the investigators concluded that pregnancy outcomes and the rate of congenital anomalies did not significantly differ from other inflammatory bowel disease patients not receiving anti-TNF drugs or the general population.¹⁵

In 2012, the National Board of the National Psoriasis Foundation put infliximab amongst the first-line treatment modalities for GPPP.² In one case of GPPP in which the eruption persisted after delivery, the patient was treated with infliximab 7 weeks postpartum due to failure to control the disease with prednisolone 60 mg daily and cyclosporine 7.5 mg/kg daily. Unlike our patient, this patient was only started on an infliximab regimen after delivery.¹⁶ In another case reported in 2010, the patient was started on infliximab during the postpartum period of her first pregnancy following a pustular flare of previously diagnosed plaque psoriasis (not a generalized pustular psoriasis, as in our case).¹⁷ As a good response was obtained, infliximab treatment was continued in the patient throughout her second pregnancy.

Our case is unique in that infliximab was started during pregnancy because of intractable disease leading to systemic symptoms. Our patient showed an excellent response to infliximab after a 10-week disease course with repeated flare-ups and impairment to her overall condition. Delivery occurred at 36 weeks’ gestation due to suspected intrauterine growth retardation; however, the neonate was born with a 5-minute APGAR score of 10 and required no special medical care, which suggests that the low birth weight was constitutional due to the patient’s small frame (her height was 4 ft 11 in). The breast milk of patients with inflammatory bowel disease has been detected to contain very small amounts of infliximab (101 ng/mL, about 1/200 of the therapeutic blood level).¹⁸ Considering the large molecular weight of this agent and possible proteolysis in the stomach and intestines, infliximab is unlikely to affect the neonate.¹⁵ Thus, we encouraged our patient to breastfeed her baby. A case of fatal disseminated Bacille-Calmette-Guérin infection in an infant whose mother received infliximab treatment during pregnancy has been reported.¹⁹ It has been suggested that live vaccines should be avoided in neonates exposed to anti-TNF agents at least for the first 6 months of life or until the agent is no longer detectable in their blood.¹⁵ We therefore informed our patient’s family practitioner about this data.

Conclusion

We report a case of infliximab treatment for GPPP that was continued during the postpartum period. Infliximab was an effective treatment option in our patient with no detected serious adverse events and may be considered in other cases of GPPP that are not responsive to systemic steroids. However, further studies are warranted to evaluate the safety and efficacy of infliximab treatment for GPPP and psoriasis in pregnancy.

Generalized pustular psoriasis of pregnancy (GPPP), formerly known as impetigo herpetiformis, is a rare dermatosis that causes maternal and fetal morbidity and mortality. It is characterized by widespread, circular, erythematous plaques with pustules at the periphery.¹ Conventional first-line treatment includes systemic corticosteroids and cyclosporine. The National Psoriasis Foundation Medical Board also has included infliximab among the first-line treatment options for GPPP.² Herein, we report a case of GPPP treated with infliximab at 30 weeks’ gestation and during the postpartum period.

Case Report

A 22-year-old woman was admitted to our inpatient clinic at 20 weeks’ gestation in her second pregnancy for evaluation of cutaneous eruptions covering the entire body. The lesions first appeared 3 to 4 days prior to her admission and dramatically progressed. She had a history of psoriasis vulgaris diagnosed during her first pregnancy 2 years prior that was treated with topical steroids throughout the pregnancy and methotrexate during lactation for a total of 11 months. She then was started on cyclosporine, which she used for 6 months due to ineffectiveness of the methotrexate, but she stopped treatment 4 months before the second pregnancy.

At the current presentation, physical examination revealed erythroderma and widespread pustules on the chest, abdomen, arms, and legs, including the intertriginous regions, that tended to coalesce and form lakes of pus over an erythematous base (Figure 1). The mucosae were normal. She exhibited a low blood pressure (85/50 mmHg) and high body temperature (102 °F [38.9 °C]). Routine laboratory examination revealed anemia and a normal leukocyte count. Her erythrocyte sedimentation rate (57 mm/h [reference range, <20 mm/h]) and C-reactive protein level (102 mg/L [reference range, <6 mg/L]) were elevated, whereas total calcium (8.11 mg/dL [reference range, 8.2–10.6 mg/dL]) and albumin (3.15 g/dL [reference range, >4.0 g/dL]) levels were low.

The patient returned to the clinic 3 weeks postpartum with a few pustules on erythematous plaques on the chest, abdomen, and back. At this time, she received a third infusion of infliximab 8 weeks after the second dose. For the past 5 years, the patient has been undergoing infliximab maintenance treatment, which she receives at the hospital every 8 weeks with excellent response. She has had no further pregnancies to date.

Comment

Generalized pustular psoriasis of pregnancy is a rare condition that typically occurs in the third trimester but also can start in the first and second trimesters. It may result in maternal and fetal morbidity by causing fluid and electrolyte imbalance and/or placental insufficiency, resulting in an increased risk for fetal abnormalities, stillbirth, and neonatal death.³ In subsequent pregnancies, GPPP has been observed to recur at an earlier gestational age with a more severe presentation.^1,3

Generalized pustular psoriasis of pregnancy usually involves an eruption that begins symmetrically in the intertriginous areas and spreads to the rest of the body. The lesions present as erythematous annular plaques with pustules on the periphery and desquamation in the center due to older pustules.^1,3 The mucous membranes also may be involved with erosive and exfoliative plaques, and there may be nail involvement. Patients often present with systemic symptoms such as fever, malaise, diarrhea, and vomiting.¹ Laboratory investigations may reveal neutrophilic leukocytosis, high erythrocyte sedimentation rate, hypocalcemia, and hypoalbuminemia.⁴ Cultures from blood and pustules show no bacterial growth. A skin biopsy is helpful in diagnosis, with features similar to generalized pustular psoriasis, demonstrating spongiform pustules containing neutrophils, lymphocytic and neutrophilic infiltrates in the papillary dermis, and negative direct immunofluorescence.³

The differential diagnosis of GPPP includes subcorneal pustular dermatosis, dermatitis herpetiformis, herpes gestationis, impetigo, and acute generalized exanthematous pustulosis.^1,3 Due to concerns of fetal implications, treatment options in GPPP are somewhat limited; however, the condition requires treatment because it may result in unfavorable pregnancy outcomes. Topical corticosteroids may be an option for limited disease.^5,6 Systemic corticosteroids (eg, prednisone 60–80 mg/d) were previously considered as first-line agents, although they have shown limited efficacy in our case as well as in other case reports.⁷ Their ineffectiveness and risk for flare-up after dose tapering should be kept in mind when starting GPPP patients on systemic corticosteroids. Systemic cyclosporine (2–3 mg/kg/d) may be added to increase the efficacy of systemic steroids, which was done in several cases in literature.^1,6,8 Although cyclosporine has been classified as a pregnancy category C drug, an analysis of pregnancy outcomes of 629 renal transplant patients revealed no association with adverse pregnancy outcomes compared to the general population and no increase in fetal malformations.⁹ Therefore, cyclosporine is a safe treatment option and was classified as a first-line drug for GPPP in a 2012 review by the National Psoriasis Foundation Medical Board.² Narrowband UVB also has been reported to be used for the treatment of GPPP.¹⁰ Methotrexate and retinoids have been used in cases with lesions that persisted postpartum.¹

Anti–tumor necrosis factor (TNF) α agents are another effective option for treatment of GPPP. Anti-TNF agents are classified as pregnancy category B due to results showing that anti-mouse TNF-α monoclonal antibodies did not cause embryotoxicity or teratogenicity in pregnant mice.¹¹ Although Carter et al¹² published a review of US Food and Drug Administration data on pregnant women receiving anti-TNF treatment and concluded that these agents were associated with the VACTERL group of malformations (vertebral defects, anal atresia, cardiac defect, tracheoesophageal fistula with esophageal atresia, cardiac defects, renal and limb anomalies), no such association was found in further studies. A 2014 study showed no difference in the rate of major malformations in infants born to women who were treated with anti-TNF drugs compared to the disease-matched group not treated with these agents and pregnant women counselled for nonteratogenic exposure.¹³ The same study detected an increase in preterm and low-birth-weight deliveries and suggested this might be caused by the increased severity of disease in patients requiring anti-TNF medication. The British Society of Rheumatology Biologics Register published data on pregnancy outcomes in 130 rheumatoid arthritis patients who had been exposed to anti-TNF agents.¹⁴ The results suggested an increased rate of spontaneous abortions in women exposed to anti-TNF treatment around the time of conception, especially in those taking these medications together with methotrexate or leflunomide; however, results also indicated that disease activity may have had an impact on the rate of spontaneous abortions in these patients. In a 2013 review of 462 women with inflammatory bowel disease who had been exposed to anti-TNF agents during pregnancy, the investigators concluded that pregnancy outcomes and the rate of congenital anomalies did not significantly differ from other inflammatory bowel disease patients not receiving anti-TNF drugs or the general population.¹⁵

In 2012, the National Board of the National Psoriasis Foundation put infliximab amongst the first-line treatment modalities for GPPP.² In one case of GPPP in which the eruption persisted after delivery, the patient was treated with infliximab 7 weeks postpartum due to failure to control the disease with prednisolone 60 mg daily and cyclosporine 7.5 mg/kg daily. Unlike our patient, this patient was only started on an infliximab regimen after delivery.¹⁶ In another case reported in 2010, the patient was started on infliximab during the postpartum period of her first pregnancy following a pustular flare of previously diagnosed plaque psoriasis (not a generalized pustular psoriasis, as in our case).¹⁷ As a good response was obtained, infliximab treatment was continued in the patient throughout her second pregnancy.

Our case is unique in that infliximab was started during pregnancy because of intractable disease leading to systemic symptoms. Our patient showed an excellent response to infliximab after a 10-week disease course with repeated flare-ups and impairment to her overall condition. Delivery occurred at 36 weeks’ gestation due to suspected intrauterine growth retardation; however, the neonate was born with a 5-minute APGAR score of 10 and required no special medical care, which suggests that the low birth weight was constitutional due to the patient’s small frame (her height was 4 ft 11 in). The breast milk of patients with inflammatory bowel disease has been detected to contain very small amounts of infliximab (101 ng/mL, about 1/200 of the therapeutic blood level).¹⁸ Considering the large molecular weight of this agent and possible proteolysis in the stomach and intestines, infliximab is unlikely to affect the neonate.¹⁵ Thus, we encouraged our patient to breastfeed her baby. A case of fatal disseminated Bacille-Calmette-Guérin infection in an infant whose mother received infliximab treatment during pregnancy has been reported.¹⁹ It has been suggested that live vaccines should be avoided in neonates exposed to anti-TNF agents at least for the first 6 months of life or until the agent is no longer detectable in their blood.¹⁵ We therefore informed our patient’s family practitioner about this data.

Conclusion

We report a case of infliximab treatment for GPPP that was continued during the postpartum period. Infliximab was an effective treatment option in our patient with no detected serious adverse events and may be considered in other cases of GPPP that are not responsive to systemic steroids. However, further studies are warranted to evaluate the safety and efficacy of infliximab treatment for GPPP and psoriasis in pregnancy.

Generalized pustular psoriasis of pregnancy (GPPP), formerly known as impetigo herpetiformis, is a rare dermatosis that causes maternal and fetal morbidity and mortality. It is characterized by widespread, circular, erythematous plaques with pustules at the periphery.¹ Conventional first-line treatment includes systemic corticosteroids and cyclosporine. The National Psoriasis Foundation Medical Board also has included infliximab among the first-line treatment options for GPPP.² Herein, we report a case of GPPP treated with infliximab at 30 weeks’ gestation and during the postpartum period.

Case Report

A 22-year-old woman was admitted to our inpatient clinic at 20 weeks’ gestation in her second pregnancy for evaluation of cutaneous eruptions covering the entire body. The lesions first appeared 3 to 4 days prior to her admission and dramatically progressed. She had a history of psoriasis vulgaris diagnosed during her first pregnancy 2 years prior that was treated with topical steroids throughout the pregnancy and methotrexate during lactation for a total of 11 months. She then was started on cyclosporine, which she used for 6 months due to ineffectiveness of the methotrexate, but she stopped treatment 4 months before the second pregnancy.

At the current presentation, physical examination revealed erythroderma and widespread pustules on the chest, abdomen, arms, and legs, including the intertriginous regions, that tended to coalesce and form lakes of pus over an erythematous base (Figure 1). The mucosae were normal. She exhibited a low blood pressure (85/50 mmHg) and high body temperature (102 °F [38.9 °C]). Routine laboratory examination revealed anemia and a normal leukocyte count. Her erythrocyte sedimentation rate (57 mm/h [reference range, <20 mm/h]) and C-reactive protein level (102 mg/L [reference range, <6 mg/L]) were elevated, whereas total calcium (8.11 mg/dL [reference range, 8.2–10.6 mg/dL]) and albumin (3.15 g/dL [reference range, >4.0 g/dL]) levels were low.

The patient returned to the clinic 3 weeks postpartum with a few pustules on erythematous plaques on the chest, abdomen, and back. At this time, she received a third infusion of infliximab 8 weeks after the second dose. For the past 5 years, the patient has been undergoing infliximab maintenance treatment, which she receives at the hospital every 8 weeks with excellent response. She has had no further pregnancies to date.

Comment

Generalized pustular psoriasis of pregnancy is a rare condition that typically occurs in the third trimester but also can start in the first and second trimesters. It may result in maternal and fetal morbidity by causing fluid and electrolyte imbalance and/or placental insufficiency, resulting in an increased risk for fetal abnormalities, stillbirth, and neonatal death.³ In subsequent pregnancies, GPPP has been observed to recur at an earlier gestational age with a more severe presentation.^1,3

Generalized pustular psoriasis of pregnancy usually involves an eruption that begins symmetrically in the intertriginous areas and spreads to the rest of the body. The lesions present as erythematous annular plaques with pustules on the periphery and desquamation in the center due to older pustules.^1,3 The mucous membranes also may be involved with erosive and exfoliative plaques, and there may be nail involvement. Patients often present with systemic symptoms such as fever, malaise, diarrhea, and vomiting.¹ Laboratory investigations may reveal neutrophilic leukocytosis, high erythrocyte sedimentation rate, hypocalcemia, and hypoalbuminemia.⁴ Cultures from blood and pustules show no bacterial growth. A skin biopsy is helpful in diagnosis, with features similar to generalized pustular psoriasis, demonstrating spongiform pustules containing neutrophils, lymphocytic and neutrophilic infiltrates in the papillary dermis, and negative direct immunofluorescence.³

The differential diagnosis of GPPP includes subcorneal pustular dermatosis, dermatitis herpetiformis, herpes gestationis, impetigo, and acute generalized exanthematous pustulosis.^1,3 Due to concerns of fetal implications, treatment options in GPPP are somewhat limited; however, the condition requires treatment because it may result in unfavorable pregnancy outcomes. Topical corticosteroids may be an option for limited disease.^5,6 Systemic corticosteroids (eg, prednisone 60–80 mg/d) were previously considered as first-line agents, although they have shown limited efficacy in our case as well as in other case reports.⁷ Their ineffectiveness and risk for flare-up after dose tapering should be kept in mind when starting GPPP patients on systemic corticosteroids. Systemic cyclosporine (2–3 mg/kg/d) may be added to increase the efficacy of systemic steroids, which was done in several cases in literature.^1,6,8 Although cyclosporine has been classified as a pregnancy category C drug, an analysis of pregnancy outcomes of 629 renal transplant patients revealed no association with adverse pregnancy outcomes compared to the general population and no increase in fetal malformations.⁹ Therefore, cyclosporine is a safe treatment option and was classified as a first-line drug for GPPP in a 2012 review by the National Psoriasis Foundation Medical Board.² Narrowband UVB also has been reported to be used for the treatment of GPPP.¹⁰ Methotrexate and retinoids have been used in cases with lesions that persisted postpartum.¹

Anti–tumor necrosis factor (TNF) α agents are another effective option for treatment of GPPP. Anti-TNF agents are classified as pregnancy category B due to results showing that anti-mouse TNF-α monoclonal antibodies did not cause embryotoxicity or teratogenicity in pregnant mice.¹¹ Although Carter et al¹² published a review of US Food and Drug Administration data on pregnant women receiving anti-TNF treatment and concluded that these agents were associated with the VACTERL group of malformations (vertebral defects, anal atresia, cardiac defect, tracheoesophageal fistula with esophageal atresia, cardiac defects, renal and limb anomalies), no such association was found in further studies. A 2014 study showed no difference in the rate of major malformations in infants born to women who were treated with anti-TNF drugs compared to the disease-matched group not treated with these agents and pregnant women counselled for nonteratogenic exposure.¹³ The same study detected an increase in preterm and low-birth-weight deliveries and suggested this might be caused by the increased severity of disease in patients requiring anti-TNF medication. The British Society of Rheumatology Biologics Register published data on pregnancy outcomes in 130 rheumatoid arthritis patients who had been exposed to anti-TNF agents.¹⁴ The results suggested an increased rate of spontaneous abortions in women exposed to anti-TNF treatment around the time of conception, especially in those taking these medications together with methotrexate or leflunomide; however, results also indicated that disease activity may have had an impact on the rate of spontaneous abortions in these patients. In a 2013 review of 462 women with inflammatory bowel disease who had been exposed to anti-TNF agents during pregnancy, the investigators concluded that pregnancy outcomes and the rate of congenital anomalies did not significantly differ from other inflammatory bowel disease patients not receiving anti-TNF drugs or the general population.¹⁵

In 2012, the National Board of the National Psoriasis Foundation put infliximab amongst the first-line treatment modalities for GPPP.² In one case of GPPP in which the eruption persisted after delivery, the patient was treated with infliximab 7 weeks postpartum due to failure to control the disease with prednisolone 60 mg daily and cyclosporine 7.5 mg/kg daily. Unlike our patient, this patient was only started on an infliximab regimen after delivery.¹⁶ In another case reported in 2010, the patient was started on infliximab during the postpartum period of her first pregnancy following a pustular flare of previously diagnosed plaque psoriasis (not a generalized pustular psoriasis, as in our case).¹⁷ As a good response was obtained, infliximab treatment was continued in the patient throughout her second pregnancy.

Our case is unique in that infliximab was started during pregnancy because of intractable disease leading to systemic symptoms. Our patient showed an excellent response to infliximab after a 10-week disease course with repeated flare-ups and impairment to her overall condition. Delivery occurred at 36 weeks’ gestation due to suspected intrauterine growth retardation; however, the neonate was born with a 5-minute APGAR score of 10 and required no special medical care, which suggests that the low birth weight was constitutional due to the patient’s small frame (her height was 4 ft 11 in). The breast milk of patients with inflammatory bowel disease has been detected to contain very small amounts of infliximab (101 ng/mL, about 1/200 of the therapeutic blood level).¹⁸ Considering the large molecular weight of this agent and possible proteolysis in the stomach and intestines, infliximab is unlikely to affect the neonate.¹⁵ Thus, we encouraged our patient to breastfeed her baby. A case of fatal disseminated Bacille-Calmette-Guérin infection in an infant whose mother received infliximab treatment during pregnancy has been reported.¹⁹ It has been suggested that live vaccines should be avoided in neonates exposed to anti-TNF agents at least for the first 6 months of life or until the agent is no longer detectable in their blood.¹⁵ We therefore informed our patient’s family practitioner about this data.

Conclusion

We report a case of infliximab treatment for GPPP that was continued during the postpartum period. Infliximab was an effective treatment option in our patient with no detected serious adverse events and may be considered in other cases of GPPP that are not responsive to systemic steroids. However, further studies are warranted to evaluate the safety and efficacy of infliximab treatment for GPPP and psoriasis in pregnancy.

Only about 30% or fewer of patients with psoriatic arthritis (PsA) on therapy achieve disease remission by any definition. One reason for this may be inadequate attention to common comorbid conditions, Alexis Ogdie, MD, MSCE, declared at the 2021 Rheumatology Winter Clinical Symposium.

Courtesy Dr. Alexis Ogdie

“I believe that addressing off-target aspects of disease is really important to improving the patient experience of their disease. We might need to target these directly in order to improve outcomes,” said Dr. Ogdie, a rheumatologist and epidemiologist at the University of Pennsylvania, Philadelphia, who coauthored the current American College of Rheumatology/National Psoriasis Foundation PsA guidelines.

Since rheumatologists are by now well informed about the increased cardiovascular risk associated with PsA, she focused on two common comorbidities that get less attention, both of which are associated with worse clinical outcomes in PsA: obesity and mental health issues.
 

Anxiety and depression

Dr. Ogdie was first author of a large, population-based, longitudinal cohort study of cause-specific mortality in 8,706 U.K. patients with PsA, 41,752 with RA, and more than 81,000 controls. Particularly striking was the finding of elevated mortality because of suicide in the rheumatic disease patients: a 203% increased risk in the PsA population, compared with the general population, and a 147% greater risk in patients with RA.

Overall, 30%-40% of PsA patients have comorbid depression and/or anxiety.

“That’s pretty striking. It’s also true for rheumatoid arthritis and axial spondyloarthritis. And if you’re depressed, you’re much less likely to respond to therapy in the way that we are measuring response to therapy,” Dr. Ogdie said.

Her approach to screening for depression and anxiety in her PsA patients, and indeed in all her other patients, is to begin by normalizing the topic, explaining to them that these affective disorders are common among patients with these disorders. She lets her patients know they can talk to her about it. And she informs them that, while effective treatment of their rheumatic disease may improve their depression or anxiety, managing those is also important for improving their disease. Additionally, understanding whether depression is present is important prior to prescribing certain medications. Apremilast (Otezla), for example, can worsen preexisting depression.

“Ask about signs and symptoms of depression,” Dr. Ogdie urged her colleagues. “I do this at every single visit in my review of symptoms. This is one I don’t skip. I ask: ‘Do you have any symptoms of depression or anxiety?’ ”

Structured evidence-based screening tools, many of which are well suited for completion during a patient’s preappointment check-in survey, include the Patient Health Questionnaire–2, the PHQ-9, the Patient-Reported Outcomes Measure Information System–10, PROMIS–Depression, and Routine Assessment of Patient Index Data 3.

“I also really like the PROMIS-29. It covers many domains of interest: depression and anxiety, sleep, fatigue, pain, physical function. It gives a lot of information about what’s going on in a patient’s life right now,” according to the rheumatologist.

The main thing is to regularly screen for anxiety and depression and then refer symptomatic patients for further assessment and treatment. This is not something that all rheumatologists have been trained to do.

Obesity

Dr. Ogdie was lead author of a national CORRONA Registry study which concluded that obese patients with PsA were only half as likely to achieve remission on a tumor necrosis factor (TNF) inhibitor, compared with nonobese patients. She believes the same holds true for all other types of therapy: Across the board, obesity is associated with a poor response. And obesity is much more common in PsA patients than the general population in every age group. Moreover, obesity is associated with risk factors for cardiovascular disease and is associated with fatty liver disease, two other major comorbid conditions in the PsA population.

The CORRONA Registry findings are supportive of an earlier Italian prospective, observational study of 135 obese and an equal number of normal-weight PsA patients, all of whom started on a TNF inhibitor and were followed for 24 months. In a multivariate-adjusted analysis, obesity was independently associated with a 390% higher risk of not achieving minimal disease activity.

The same Italian group subsequently conducted a prospective dietary intervention study in 138 overweight or obese patients with PsA starting anti-TNF therapy. A total of 59% of participants randomized to either of the two dietary interventions experienced at least a 5% weight loss at 6 months. The key study finding: Compared with the subjects with less than 5% weight loss, those with 5%-10% weight loss were 275% more likely to achieve minimal disease activity at 6 months, and in those with greater than 10% weight loss the likelihood of attaining minimal disease activity increased by 567%.

“We’re talking about a disease where treatments tested in clinical trials have odds ratios in the 1.2 range, compared with other therapies, so this is a really striking difference,” she observed.

Several studies have demonstrated that obesity in psoriasis patients is a risk factor for developing PsA. Recently, U.K. investigators took things a step further, reporting in a huge observational study that obese or overweight psoriasis patients who reduced their body mass index over a 10-year period had a corresponding reduction in the risk of developing PsA, compared with overweight or obese psoriasis patients whose BMI remained steady over the same period.

What’s needed now is access to programs to help patients with PsA lose weight. Health insurers are often unwilling to provide coverage. “We have a really tough time getting the patients in to see a nutritionist unless they’re willing to pay out of pocket,” Dr. Ogdie said.

Physical activity is an important element in successful weight loss. It also is recommended in practice guidelines for patients with inflammatory arthritis because of its salutary effects on disease activity scores, pain and stiffness, sleep, and quality of life. But a recent survey conducted by Dr. Ogdie and coworkers concluded that patients with PsA and other forms of inflammatory arthritis don’t receive much exercise guidance from their rheumatologists. About 60% of subjects were inactive. Those who were physically active typically engaged in aerobic exercise but were much less likely to do the other guideline-recommended forms of exercise, namely flexibility, balance, and resistance training. The patients’ report of low engagement of their physicians “suggests an opportunity for more prescriptive exercise discussions,” according to the investigators.

Diabetes, a critical risk factor for cardiovascular disease, occurs at an increased incidence in PsA. This was demonstrated in a U.K. cohort study coauthored by Dr. Ogdie. The study, which included nearly 4,200 individuals with PsA, concluded that they had a 43% greater incidence of diabetes than the general population in an analysis adjusted for body mass index, smoking, alcohol use, and demographics.

New-onset diabetes can be readily picked up by rheumatologists based upon the laboratory work they often order at patient office visits, or during their review of symptoms, she noted, and added that the U.S. Preventive Services Task Force recommends ordering a hemoglobin A1c test every 3 years.

Dr. Ogdie reported receiving research grants and/or consulting fees from numerous pharmaceutical companies. Her research is also funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the Rheumatology Research Foundation, and the National Psoriasis Foundation.

bjancin@mdedge.com

Only about 30% or fewer of patients with psoriatic arthritis (PsA) on therapy achieve disease remission by any definition. One reason for this may be inadequate attention to common comorbid conditions, Alexis Ogdie, MD, MSCE, declared at the 2021 Rheumatology Winter Clinical Symposium.

Courtesy Dr. Alexis Ogdie

“I believe that addressing off-target aspects of disease is really important to improving the patient experience of their disease. We might need to target these directly in order to improve outcomes,” said Dr. Ogdie, a rheumatologist and epidemiologist at the University of Pennsylvania, Philadelphia, who coauthored the current American College of Rheumatology/National Psoriasis Foundation PsA guidelines.

Since rheumatologists are by now well informed about the increased cardiovascular risk associated with PsA, she focused on two common comorbidities that get less attention, both of which are associated with worse clinical outcomes in PsA: obesity and mental health issues.
 

Anxiety and depression

Dr. Ogdie was first author of a large, population-based, longitudinal cohort study of cause-specific mortality in 8,706 U.K. patients with PsA, 41,752 with RA, and more than 81,000 controls. Particularly striking was the finding of elevated mortality because of suicide in the rheumatic disease patients: a 203% increased risk in the PsA population, compared with the general population, and a 147% greater risk in patients with RA.

Overall, 30%-40% of PsA patients have comorbid depression and/or anxiety.

“That’s pretty striking. It’s also true for rheumatoid arthritis and axial spondyloarthritis. And if you’re depressed, you’re much less likely to respond to therapy in the way that we are measuring response to therapy,” Dr. Ogdie said.

Her approach to screening for depression and anxiety in her PsA patients, and indeed in all her other patients, is to begin by normalizing the topic, explaining to them that these affective disorders are common among patients with these disorders. She lets her patients know they can talk to her about it. And she informs them that, while effective treatment of their rheumatic disease may improve their depression or anxiety, managing those is also important for improving their disease. Additionally, understanding whether depression is present is important prior to prescribing certain medications. Apremilast (Otezla), for example, can worsen preexisting depression.

“Ask about signs and symptoms of depression,” Dr. Ogdie urged her colleagues. “I do this at every single visit in my review of symptoms. This is one I don’t skip. I ask: ‘Do you have any symptoms of depression or anxiety?’ ”

Structured evidence-based screening tools, many of which are well suited for completion during a patient’s preappointment check-in survey, include the Patient Health Questionnaire–2, the PHQ-9, the Patient-Reported Outcomes Measure Information System–10, PROMIS–Depression, and Routine Assessment of Patient Index Data 3.

“I also really like the PROMIS-29. It covers many domains of interest: depression and anxiety, sleep, fatigue, pain, physical function. It gives a lot of information about what’s going on in a patient’s life right now,” according to the rheumatologist.

The main thing is to regularly screen for anxiety and depression and then refer symptomatic patients for further assessment and treatment. This is not something that all rheumatologists have been trained to do.

Obesity

Dr. Ogdie was lead author of a national CORRONA Registry study which concluded that obese patients with PsA were only half as likely to achieve remission on a tumor necrosis factor (TNF) inhibitor, compared with nonobese patients. She believes the same holds true for all other types of therapy: Across the board, obesity is associated with a poor response. And obesity is much more common in PsA patients than the general population in every age group. Moreover, obesity is associated with risk factors for cardiovascular disease and is associated with fatty liver disease, two other major comorbid conditions in the PsA population.

The CORRONA Registry findings are supportive of an earlier Italian prospective, observational study of 135 obese and an equal number of normal-weight PsA patients, all of whom started on a TNF inhibitor and were followed for 24 months. In a multivariate-adjusted analysis, obesity was independently associated with a 390% higher risk of not achieving minimal disease activity.

The same Italian group subsequently conducted a prospective dietary intervention study in 138 overweight or obese patients with PsA starting anti-TNF therapy. A total of 59% of participants randomized to either of the two dietary interventions experienced at least a 5% weight loss at 6 months. The key study finding: Compared with the subjects with less than 5% weight loss, those with 5%-10% weight loss were 275% more likely to achieve minimal disease activity at 6 months, and in those with greater than 10% weight loss the likelihood of attaining minimal disease activity increased by 567%.

“We’re talking about a disease where treatments tested in clinical trials have odds ratios in the 1.2 range, compared with other therapies, so this is a really striking difference,” she observed.

Several studies have demonstrated that obesity in psoriasis patients is a risk factor for developing PsA. Recently, U.K. investigators took things a step further, reporting in a huge observational study that obese or overweight psoriasis patients who reduced their body mass index over a 10-year period had a corresponding reduction in the risk of developing PsA, compared with overweight or obese psoriasis patients whose BMI remained steady over the same period.

What’s needed now is access to programs to help patients with PsA lose weight. Health insurers are often unwilling to provide coverage. “We have a really tough time getting the patients in to see a nutritionist unless they’re willing to pay out of pocket,” Dr. Ogdie said.

Physical activity is an important element in successful weight loss. It also is recommended in practice guidelines for patients with inflammatory arthritis because of its salutary effects on disease activity scores, pain and stiffness, sleep, and quality of life. But a recent survey conducted by Dr. Ogdie and coworkers concluded that patients with PsA and other forms of inflammatory arthritis don’t receive much exercise guidance from their rheumatologists. About 60% of subjects were inactive. Those who were physically active typically engaged in aerobic exercise but were much less likely to do the other guideline-recommended forms of exercise, namely flexibility, balance, and resistance training. The patients’ report of low engagement of their physicians “suggests an opportunity for more prescriptive exercise discussions,” according to the investigators.

Diabetes, a critical risk factor for cardiovascular disease, occurs at an increased incidence in PsA. This was demonstrated in a U.K. cohort study coauthored by Dr. Ogdie. The study, which included nearly 4,200 individuals with PsA, concluded that they had a 43% greater incidence of diabetes than the general population in an analysis adjusted for body mass index, smoking, alcohol use, and demographics.

New-onset diabetes can be readily picked up by rheumatologists based upon the laboratory work they often order at patient office visits, or during their review of symptoms, she noted, and added that the U.S. Preventive Services Task Force recommends ordering a hemoglobin A1c test every 3 years.

Dr. Ogdie reported receiving research grants and/or consulting fees from numerous pharmaceutical companies. Her research is also funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the Rheumatology Research Foundation, and the National Psoriasis Foundation.

bjancin@mdedge.com

Only about 30% or fewer of patients with psoriatic arthritis (PsA) on therapy achieve disease remission by any definition. One reason for this may be inadequate attention to common comorbid conditions, Alexis Ogdie, MD, MSCE, declared at the 2021 Rheumatology Winter Clinical Symposium.

Courtesy Dr. Alexis Ogdie

“I believe that addressing off-target aspects of disease is really important to improving the patient experience of their disease. We might need to target these directly in order to improve outcomes,” said Dr. Ogdie, a rheumatologist and epidemiologist at the University of Pennsylvania, Philadelphia, who coauthored the current American College of Rheumatology/National Psoriasis Foundation PsA guidelines.

Since rheumatologists are by now well informed about the increased cardiovascular risk associated with PsA, she focused on two common comorbidities that get less attention, both of which are associated with worse clinical outcomes in PsA: obesity and mental health issues.
 

Anxiety and depression

Dr. Ogdie was first author of a large, population-based, longitudinal cohort study of cause-specific mortality in 8,706 U.K. patients with PsA, 41,752 with RA, and more than 81,000 controls. Particularly striking was the finding of elevated mortality because of suicide in the rheumatic disease patients: a 203% increased risk in the PsA population, compared with the general population, and a 147% greater risk in patients with RA.

Overall, 30%-40% of PsA patients have comorbid depression and/or anxiety.

“That’s pretty striking. It’s also true for rheumatoid arthritis and axial spondyloarthritis. And if you’re depressed, you’re much less likely to respond to therapy in the way that we are measuring response to therapy,” Dr. Ogdie said.

Her approach to screening for depression and anxiety in her PsA patients, and indeed in all her other patients, is to begin by normalizing the topic, explaining to them that these affective disorders are common among patients with these disorders. She lets her patients know they can talk to her about it. And she informs them that, while effective treatment of their rheumatic disease may improve their depression or anxiety, managing those is also important for improving their disease. Additionally, understanding whether depression is present is important prior to prescribing certain medications. Apremilast (Otezla), for example, can worsen preexisting depression.

“Ask about signs and symptoms of depression,” Dr. Ogdie urged her colleagues. “I do this at every single visit in my review of symptoms. This is one I don’t skip. I ask: ‘Do you have any symptoms of depression or anxiety?’ ”

Structured evidence-based screening tools, many of which are well suited for completion during a patient’s preappointment check-in survey, include the Patient Health Questionnaire–2, the PHQ-9, the Patient-Reported Outcomes Measure Information System–10, PROMIS–Depression, and Routine Assessment of Patient Index Data 3.

“I also really like the PROMIS-29. It covers many domains of interest: depression and anxiety, sleep, fatigue, pain, physical function. It gives a lot of information about what’s going on in a patient’s life right now,” according to the rheumatologist.

The main thing is to regularly screen for anxiety and depression and then refer symptomatic patients for further assessment and treatment. This is not something that all rheumatologists have been trained to do.

Obesity

Dr. Ogdie was lead author of a national CORRONA Registry study which concluded that obese patients with PsA were only half as likely to achieve remission on a tumor necrosis factor (TNF) inhibitor, compared with nonobese patients. She believes the same holds true for all other types of therapy: Across the board, obesity is associated with a poor response. And obesity is much more common in PsA patients than the general population in every age group. Moreover, obesity is associated with risk factors for cardiovascular disease and is associated with fatty liver disease, two other major comorbid conditions in the PsA population.

The CORRONA Registry findings are supportive of an earlier Italian prospective, observational study of 135 obese and an equal number of normal-weight PsA patients, all of whom started on a TNF inhibitor and were followed for 24 months. In a multivariate-adjusted analysis, obesity was independently associated with a 390% higher risk of not achieving minimal disease activity.

The same Italian group subsequently conducted a prospective dietary intervention study in 138 overweight or obese patients with PsA starting anti-TNF therapy. A total of 59% of participants randomized to either of the two dietary interventions experienced at least a 5% weight loss at 6 months. The key study finding: Compared with the subjects with less than 5% weight loss, those with 5%-10% weight loss were 275% more likely to achieve minimal disease activity at 6 months, and in those with greater than 10% weight loss the likelihood of attaining minimal disease activity increased by 567%.

“We’re talking about a disease where treatments tested in clinical trials have odds ratios in the 1.2 range, compared with other therapies, so this is a really striking difference,” she observed.

Several studies have demonstrated that obesity in psoriasis patients is a risk factor for developing PsA. Recently, U.K. investigators took things a step further, reporting in a huge observational study that obese or overweight psoriasis patients who reduced their body mass index over a 10-year period had a corresponding reduction in the risk of developing PsA, compared with overweight or obese psoriasis patients whose BMI remained steady over the same period.

What’s needed now is access to programs to help patients with PsA lose weight. Health insurers are often unwilling to provide coverage. “We have a really tough time getting the patients in to see a nutritionist unless they’re willing to pay out of pocket,” Dr. Ogdie said.

Physical activity is an important element in successful weight loss. It also is recommended in practice guidelines for patients with inflammatory arthritis because of its salutary effects on disease activity scores, pain and stiffness, sleep, and quality of life. But a recent survey conducted by Dr. Ogdie and coworkers concluded that patients with PsA and other forms of inflammatory arthritis don’t receive much exercise guidance from their rheumatologists. About 60% of subjects were inactive. Those who were physically active typically engaged in aerobic exercise but were much less likely to do the other guideline-recommended forms of exercise, namely flexibility, balance, and resistance training. The patients’ report of low engagement of their physicians “suggests an opportunity for more prescriptive exercise discussions,” according to the investigators.

Diabetes, a critical risk factor for cardiovascular disease, occurs at an increased incidence in PsA. This was demonstrated in a U.K. cohort study coauthored by Dr. Ogdie. The study, which included nearly 4,200 individuals with PsA, concluded that they had a 43% greater incidence of diabetes than the general population in an analysis adjusted for body mass index, smoking, alcohol use, and demographics.

New-onset diabetes can be readily picked up by rheumatologists based upon the laboratory work they often order at patient office visits, or during their review of symptoms, she noted, and added that the U.S. Preventive Services Task Force recommends ordering a hemoglobin A1c test every 3 years.

Dr. Ogdie reported receiving research grants and/or consulting fees from numerous pharmaceutical companies. Her research is also funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the Rheumatology Research Foundation, and the National Psoriasis Foundation.

bjancin@mdedge.com

Several surprising recent insights into the pathophysiology of psoriasis may eventually lead to superior treatment strategies for this common T-cell-mediated disease, Kenneth Brian Gordon, MD, said at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually.

Courtesy National Psoriasis Foundation

Among these unexpected developments was the startling finding that skin inflammation in mild psoriasis is at least as great as in severe disease; evidence that psoriasis may actually be an autoimmune disease rather than a nonspecific immune-mediated disease; and the newly appreciated importance of interleukin-19 (IL-19) in keratinocyte proliferation, according to Dr. Gordon, professor and chair of the department of dermatology at the Medical College of Wisconsin, Milwaukee.

Immunoregulatory deficits in mild vs. severe psoriasis

Conventional wisdom has held that mild psoriasis as defined by limited affected body surface area involves less skin inflammation than more extensive severe psoriasis, so less-potent topical therapies are appropriate. Not so, according to Dr. Gordon, who highlighted work by James G. Krueger, MD, PhD, head of the laboratory of investigative dermatology at Rockefeller University, New York, and coinvestigators. They demonstrated that overall skin inflammation expressed as the sum of T-cell activation and IL-19-mediated epidermal responses didn’t differ in lesions of mild as compared with severe psoriasis. Indeed, mild skin lesions featured a greater number of T-cells, stronger expression of proinflammatory cytokine IL-17A, and greater expression of the central psoriasis transcriptome. The big difference between skin lesions of mild versus severe psoriasis was that severe psoriasis was characterized by strikingly weaker expression of immunoregulatory genes, including programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA4), than that of mild lesions.

The implication is that IL-17-targeted therapies may be of benefit in a much larger segment of the psoriatic population: namely, those with mild disease, who comprise the majority of psoriasis patients by a wide margin, according to the investigators.

Dr. Gordon concurs.

“The primary problem in psoriasis is not so much the inflammatory activity, but the ability to turn off the activity,” he explained. “That implies that if a patient wants to get clear or have significant improvement in disease, you can’t use a less effective medication just because they have less amount of disease. You’re going to need to treat it just as aggressively because the great majority of our medications block the proinflammatory pathways.”

The deficit in immunoregulatory action identified by Dr. Krueger and colleagues in patients with severe disease could provide a novel therapeutic target. If the deficient immunoregulation could be boosted, it might achieve disease control without need for continuous anti-inflammatory therapy.

 

Autoimmunity in psoriasis

“When I started work in psoriasis, we always thought there would be a common antigen for the immune process in the disease. We never found it. So for that reason, we sort of put it aside and called psoriasis a nonspecific immune-mediated disease,” Dr. Gordon recalled.

That view is being reexamined. “While we’re not completely certain, there is now some evidence that there might be autoimmunity in psoriasis,” he said.

He cited work by an international team of investigators who identified the cathelicidin antimicrobial peptide LL37 as being overexpressed in psoriatic skin, where it appears to serve as a T-cell autoantigen. LL37-specific CD4+ and CD8+ T-cells are skin homing: They can infiltrate lesional skin, where they produce interferon-gamma and proinflammatory Th17 cytokines. The investigators reported that levels of circulating LL37-specific T cells correlated with disease activity such that they were found in three-quarters of patients with moderate to severe plaque psoriasis.

“As LL37 is able to activate innate immune cells and break innate tolerance to self-nucleic acids, it represents an even more appealing target to treat psoriasis. Therapeutic targeting of LL37-specific T cells may provide new avenues to prevent or treat psoriasis without inducing indiscriminate immunosuppression,” the investigators concluded.

Similarly, German investigators have identified ADAMTS-like protein 5 (ADAMTSL5) as an autoantigen specific for melanocytes in psoriasis patients who possess the central psoriasis risk gene, known as HLA-C*06:02, which is present in two-thirds of patients with psoriasis. They proposed that their newly recognized autoimmune pathway may explain how HLA-C*06.02 predisposes to psoriasis.

Growing clinical relevance of IL-19

It’s now well-established that IL-17 is the pivotal force driving the changes in keratinocytes that define the visible expressions of psoriasis, including plaque scale and thickness, which are due to abnormal keratinocyte maturation and proliferation, respectively. Less well appreciated is the fact that IL-17-activated keratinocytes produce IL-19, which feeds back and further stimulates keratinocyte proliferation.

In light of mounting evidence that IL-19 plays an important role in the pathogenesis of psoriasis and that naked eye assessment of visible psoriasis may not reflect the true extent of inflammation, Brian J. Nickoloff, MD, PhD, and coworkers at Lilly Research Laboratories have developed a novel serum IL-19 immunoassay that appears to provide a much-needed objective biomarker of disease activity in psoriasis patients. They demonstrated that serum IL-19 levels correlated with Psoriasis Area and Severity Index scores, and that treatment with the anti-IL-17A biologic ixekizumab (Taltz) led to rapid reduction of IL-19 down to a normal level.

Moreover, following withdrawal of ixekizumab, IL-19 levels rose prior to clinical relapse, then dropped again in response to retreatment. The hope is that this assay will serve as an accurate tool for assessment of response to therapy.

Dr. Gordon reported receiving research funding and/or honoraria from more than a dozen pharmaceutical companies involved in psoriasis therapy.

MedscapeLive and this news organization are owned by the same parent company.

bjancin@mdedge.com

Several surprising recent insights into the pathophysiology of psoriasis may eventually lead to superior treatment strategies for this common T-cell-mediated disease, Kenneth Brian Gordon, MD, said at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually.

Courtesy National Psoriasis Foundation

Among these unexpected developments was the startling finding that skin inflammation in mild psoriasis is at least as great as in severe disease; evidence that psoriasis may actually be an autoimmune disease rather than a nonspecific immune-mediated disease; and the newly appreciated importance of interleukin-19 (IL-19) in keratinocyte proliferation, according to Dr. Gordon, professor and chair of the department of dermatology at the Medical College of Wisconsin, Milwaukee.

Immunoregulatory deficits in mild vs. severe psoriasis

Conventional wisdom has held that mild psoriasis as defined by limited affected body surface area involves less skin inflammation than more extensive severe psoriasis, so less-potent topical therapies are appropriate. Not so, according to Dr. Gordon, who highlighted work by James G. Krueger, MD, PhD, head of the laboratory of investigative dermatology at Rockefeller University, New York, and coinvestigators. They demonstrated that overall skin inflammation expressed as the sum of T-cell activation and IL-19-mediated epidermal responses didn’t differ in lesions of mild as compared with severe psoriasis. Indeed, mild skin lesions featured a greater number of T-cells, stronger expression of proinflammatory cytokine IL-17A, and greater expression of the central psoriasis transcriptome. The big difference between skin lesions of mild versus severe psoriasis was that severe psoriasis was characterized by strikingly weaker expression of immunoregulatory genes, including programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA4), than that of mild lesions.

The implication is that IL-17-targeted therapies may be of benefit in a much larger segment of the psoriatic population: namely, those with mild disease, who comprise the majority of psoriasis patients by a wide margin, according to the investigators.

Dr. Gordon concurs.

“The primary problem in psoriasis is not so much the inflammatory activity, but the ability to turn off the activity,” he explained. “That implies that if a patient wants to get clear or have significant improvement in disease, you can’t use a less effective medication just because they have less amount of disease. You’re going to need to treat it just as aggressively because the great majority of our medications block the proinflammatory pathways.”

The deficit in immunoregulatory action identified by Dr. Krueger and colleagues in patients with severe disease could provide a novel therapeutic target. If the deficient immunoregulation could be boosted, it might achieve disease control without need for continuous anti-inflammatory therapy.

 

Autoimmunity in psoriasis

“When I started work in psoriasis, we always thought there would be a common antigen for the immune process in the disease. We never found it. So for that reason, we sort of put it aside and called psoriasis a nonspecific immune-mediated disease,” Dr. Gordon recalled.

That view is being reexamined. “While we’re not completely certain, there is now some evidence that there might be autoimmunity in psoriasis,” he said.

He cited work by an international team of investigators who identified the cathelicidin antimicrobial peptide LL37 as being overexpressed in psoriatic skin, where it appears to serve as a T-cell autoantigen. LL37-specific CD4+ and CD8+ T-cells are skin homing: They can infiltrate lesional skin, where they produce interferon-gamma and proinflammatory Th17 cytokines. The investigators reported that levels of circulating LL37-specific T cells correlated with disease activity such that they were found in three-quarters of patients with moderate to severe plaque psoriasis.

“As LL37 is able to activate innate immune cells and break innate tolerance to self-nucleic acids, it represents an even more appealing target to treat psoriasis. Therapeutic targeting of LL37-specific T cells may provide new avenues to prevent or treat psoriasis without inducing indiscriminate immunosuppression,” the investigators concluded.

Similarly, German investigators have identified ADAMTS-like protein 5 (ADAMTSL5) as an autoantigen specific for melanocytes in psoriasis patients who possess the central psoriasis risk gene, known as HLA-C*06:02, which is present in two-thirds of patients with psoriasis. They proposed that their newly recognized autoimmune pathway may explain how HLA-C*06.02 predisposes to psoriasis.

Growing clinical relevance of IL-19

It’s now well-established that IL-17 is the pivotal force driving the changes in keratinocytes that define the visible expressions of psoriasis, including plaque scale and thickness, which are due to abnormal keratinocyte maturation and proliferation, respectively. Less well appreciated is the fact that IL-17-activated keratinocytes produce IL-19, which feeds back and further stimulates keratinocyte proliferation.

In light of mounting evidence that IL-19 plays an important role in the pathogenesis of psoriasis and that naked eye assessment of visible psoriasis may not reflect the true extent of inflammation, Brian J. Nickoloff, MD, PhD, and coworkers at Lilly Research Laboratories have developed a novel serum IL-19 immunoassay that appears to provide a much-needed objective biomarker of disease activity in psoriasis patients. They demonstrated that serum IL-19 levels correlated with Psoriasis Area and Severity Index scores, and that treatment with the anti-IL-17A biologic ixekizumab (Taltz) led to rapid reduction of IL-19 down to a normal level.

Moreover, following withdrawal of ixekizumab, IL-19 levels rose prior to clinical relapse, then dropped again in response to retreatment. The hope is that this assay will serve as an accurate tool for assessment of response to therapy.

Dr. Gordon reported receiving research funding and/or honoraria from more than a dozen pharmaceutical companies involved in psoriasis therapy.

MedscapeLive and this news organization are owned by the same parent company.

bjancin@mdedge.com

Several surprising recent insights into the pathophysiology of psoriasis may eventually lead to superior treatment strategies for this common T-cell-mediated disease, Kenneth Brian Gordon, MD, said at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually.

Courtesy National Psoriasis Foundation

Among these unexpected developments was the startling finding that skin inflammation in mild psoriasis is at least as great as in severe disease; evidence that psoriasis may actually be an autoimmune disease rather than a nonspecific immune-mediated disease; and the newly appreciated importance of interleukin-19 (IL-19) in keratinocyte proliferation, according to Dr. Gordon, professor and chair of the department of dermatology at the Medical College of Wisconsin, Milwaukee.

Immunoregulatory deficits in mild vs. severe psoriasis

Conventional wisdom has held that mild psoriasis as defined by limited affected body surface area involves less skin inflammation than more extensive severe psoriasis, so less-potent topical therapies are appropriate. Not so, according to Dr. Gordon, who highlighted work by James G. Krueger, MD, PhD, head of the laboratory of investigative dermatology at Rockefeller University, New York, and coinvestigators. They demonstrated that overall skin inflammation expressed as the sum of T-cell activation and IL-19-mediated epidermal responses didn’t differ in lesions of mild as compared with severe psoriasis. Indeed, mild skin lesions featured a greater number of T-cells, stronger expression of proinflammatory cytokine IL-17A, and greater expression of the central psoriasis transcriptome. The big difference between skin lesions of mild versus severe psoriasis was that severe psoriasis was characterized by strikingly weaker expression of immunoregulatory genes, including programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA4), than that of mild lesions.

The implication is that IL-17-targeted therapies may be of benefit in a much larger segment of the psoriatic population: namely, those with mild disease, who comprise the majority of psoriasis patients by a wide margin, according to the investigators.

Dr. Gordon concurs.

“The primary problem in psoriasis is not so much the inflammatory activity, but the ability to turn off the activity,” he explained. “That implies that if a patient wants to get clear or have significant improvement in disease, you can’t use a less effective medication just because they have less amount of disease. You’re going to need to treat it just as aggressively because the great majority of our medications block the proinflammatory pathways.”

The deficit in immunoregulatory action identified by Dr. Krueger and colleagues in patients with severe disease could provide a novel therapeutic target. If the deficient immunoregulation could be boosted, it might achieve disease control without need for continuous anti-inflammatory therapy.

 

Autoimmunity in psoriasis

“When I started work in psoriasis, we always thought there would be a common antigen for the immune process in the disease. We never found it. So for that reason, we sort of put it aside and called psoriasis a nonspecific immune-mediated disease,” Dr. Gordon recalled.

That view is being reexamined. “While we’re not completely certain, there is now some evidence that there might be autoimmunity in psoriasis,” he said.

He cited work by an international team of investigators who identified the cathelicidin antimicrobial peptide LL37 as being overexpressed in psoriatic skin, where it appears to serve as a T-cell autoantigen. LL37-specific CD4+ and CD8+ T-cells are skin homing: They can infiltrate lesional skin, where they produce interferon-gamma and proinflammatory Th17 cytokines. The investigators reported that levels of circulating LL37-specific T cells correlated with disease activity such that they were found in three-quarters of patients with moderate to severe plaque psoriasis.

“As LL37 is able to activate innate immune cells and break innate tolerance to self-nucleic acids, it represents an even more appealing target to treat psoriasis. Therapeutic targeting of LL37-specific T cells may provide new avenues to prevent or treat psoriasis without inducing indiscriminate immunosuppression,” the investigators concluded.

Similarly, German investigators have identified ADAMTS-like protein 5 (ADAMTSL5) as an autoantigen specific for melanocytes in psoriasis patients who possess the central psoriasis risk gene, known as HLA-C*06:02, which is present in two-thirds of patients with psoriasis. They proposed that their newly recognized autoimmune pathway may explain how HLA-C*06.02 predisposes to psoriasis.

Growing clinical relevance of IL-19

It’s now well-established that IL-17 is the pivotal force driving the changes in keratinocytes that define the visible expressions of psoriasis, including plaque scale and thickness, which are due to abnormal keratinocyte maturation and proliferation, respectively. Less well appreciated is the fact that IL-17-activated keratinocytes produce IL-19, which feeds back and further stimulates keratinocyte proliferation.

In light of mounting evidence that IL-19 plays an important role in the pathogenesis of psoriasis and that naked eye assessment of visible psoriasis may not reflect the true extent of inflammation, Brian J. Nickoloff, MD, PhD, and coworkers at Lilly Research Laboratories have developed a novel serum IL-19 immunoassay that appears to provide a much-needed objective biomarker of disease activity in psoriasis patients. They demonstrated that serum IL-19 levels correlated with Psoriasis Area and Severity Index scores, and that treatment with the anti-IL-17A biologic ixekizumab (Taltz) led to rapid reduction of IL-19 down to a normal level.

Moreover, following withdrawal of ixekizumab, IL-19 levels rose prior to clinical relapse, then dropped again in response to retreatment. The hope is that this assay will serve as an accurate tool for assessment of response to therapy.

Dr. Gordon reported receiving research funding and/or honoraria from more than a dozen pharmaceutical companies involved in psoriasis therapy.

MedscapeLive and this news organization are owned by the same parent company.

bjancin@mdedge.com

To the Editor:

The evolution in the understanding of psoriasis and psoriatic arthritis has unfolded many new facets of this immune-mediated inflammatory disease. Once considered to be just a cutaneous disease, psoriasis is not actually confined to skin but can involve almost any other system of the body. Cardiovascular morbidity and mortality are the major concerns in patients with psoriasis. We report the sudden death of a young man with severe psoriasis.

A 31-year-old man was admitted for severe psoriasis with pustular exacerbation (Figures 1A and 1B). He had moderate to severe unstable disease during the last 8 years and was managed with oral methotrexate (0.3–0.5 mg/kg/wk). He was not compliant with treatment, which led to multiple relapses. There was no personal or family history of risk factors for cardiovascular events (CVEs). At the time of present hospitalization, his vital parameters were normal. Physical examination revealed erythematous scaly plaques on more than 75% of the body surface area. Multiple pustules also were noted, often coalescing to form plaques (Figure 1C). Baseline investigations consisting of complete blood cell count, lipid profile, liver and renal functions, and chest radiography were within reference range. Baseline electrocardiogram (ECG) at admission was unremarkable (Figure 2A), except for sinus tachycardia. Low-voltage complexes in limb leads were appreciated as well as a corrected QT interval of 420 milliseconds (within reference range). Echocardiography was normal (visual ejection fraction of 60%).

The patient was unable to tolerate methotrexate due to excessive nausea; he was started on oral acitretin 25 mg once daily. There was no improvement in psoriasis over the following week, and he reported mild upper abdominal discomfort. He did not have any chest pain or dyspnea, and his pulse and blood pressure were normal. Serum electrolytes, liver function, lipid profile, and an ultrasound of the abdomen revealed no abnormalities. A repeat ECG showed no changes, and cardiac biomarkers were not elevated. Two days later, the patient collapsed while still in the hospital. A cardiac monitor and ECG showed ventricular tachycardia (VT)(Figure 2B); however, serum electrolytes, calcium, magnesium, and phosphorus levels were within reference range. Aggressive resuscitative measures including multiple attempts at cardioversion with up to 200 J (biphasic) and intravenous amiodarone infusion failed to revive the patient, and he died.

Proinflammatory cytokines such as IL-6 and tumor necrosis factor α are increased in young people with ventricular arrhythmias who have no evidence of myocardial injury (MI), suggesting an inflammatory background is involved.¹ Psoriasis, a common immune-mediated inflammatory disease, has a chronic state of systemic inflammation with notably higher serum levels of tumor necrosis factor α, IFN-γ, IL-6, IL-8, IL-12, and IL-18 compared to controls.² This inflammation is not confined to skin but can involve blood vessels, joints, and the liver, as demonstrated by increased fluorodeoxyglucose uptake.³ It also seems to exert its influence on supraventricular beat development in patients with psoriasis who do not have a history of CVEs.⁴ Tumor necrosis factor α is one of the major cytokines playing a role in the inflammatory process of psoriasis. Studies have shown serum levels of tumor necrosis factor α to correlate with the clinical symptoms of heart failure and to supraventricular arrhythmia in animal models.⁴ Various extreme CVEs can be an expression of this ongoing dynamic process. It would be interesting to know which specific factors among these inflammatory cytokines lead to rhythm irregularities.

Another theory is that young patients may experience micro-MI during the disease course. These small infarcted areas may act as aberrant pulse generators or lead to conduction disturbances. One study found increased correct QT interval dispersion, a predictor of ventricular arrhythmias, to be associated with psoriasis.⁵ A nationwide population-based matched cohort study by Chiu et al⁶ revealed that patients with psoriasis have a higher risk for arrhythmia independent of traditional cardiovascular risk factors. Our patient also had severe unstable psoriasis for 8 years that may have led to increased accumulation of proarrhythmogenic cytokines in the heart and could have led to VT.

Acitretin as a potential cause of sudden cardiac death remains a possibility in our case; however, the exact mechanism leading to such sudden arrhythmia is lacking. Acitretin is known to increase serum triglycerides and cholesterol, specifically by shifting high-density lipoproteins to low-density lipoproteins, thereby increasing the risk for CVE. However, it takes time for such derangement to occur, eventually leading to CVE. Mittal et al⁷ reported a psoriasis patient who died secondary to MI after 5 days of low-dose acitretin. Lack of evidence makes acitretin a less likely cause of mortality.

We present a case of sudden cardiac death secondary to VT in a young patient with psoriasis and no other traditional cardiovascular risk factors. This case highlights the importance of being vigilant for adverse CVEs such as arrhythmia in psoriatic patients, especially in younger patients with severe unstable disease.

To the Editor:

The evolution in the understanding of psoriasis and psoriatic arthritis has unfolded many new facets of this immune-mediated inflammatory disease. Once considered to be just a cutaneous disease, psoriasis is not actually confined to skin but can involve almost any other system of the body. Cardiovascular morbidity and mortality are the major concerns in patients with psoriasis. We report the sudden death of a young man with severe psoriasis.

A 31-year-old man was admitted for severe psoriasis with pustular exacerbation (Figures 1A and 1B). He had moderate to severe unstable disease during the last 8 years and was managed with oral methotrexate (0.3–0.5 mg/kg/wk). He was not compliant with treatment, which led to multiple relapses. There was no personal or family history of risk factors for cardiovascular events (CVEs). At the time of present hospitalization, his vital parameters were normal. Physical examination revealed erythematous scaly plaques on more than 75% of the body surface area. Multiple pustules also were noted, often coalescing to form plaques (Figure 1C). Baseline investigations consisting of complete blood cell count, lipid profile, liver and renal functions, and chest radiography were within reference range. Baseline electrocardiogram (ECG) at admission was unremarkable (Figure 2A), except for sinus tachycardia. Low-voltage complexes in limb leads were appreciated as well as a corrected QT interval of 420 milliseconds (within reference range). Echocardiography was normal (visual ejection fraction of 60%).

The patient was unable to tolerate methotrexate due to excessive nausea; he was started on oral acitretin 25 mg once daily. There was no improvement in psoriasis over the following week, and he reported mild upper abdominal discomfort. He did not have any chest pain or dyspnea, and his pulse and blood pressure were normal. Serum electrolytes, liver function, lipid profile, and an ultrasound of the abdomen revealed no abnormalities. A repeat ECG showed no changes, and cardiac biomarkers were not elevated. Two days later, the patient collapsed while still in the hospital. A cardiac monitor and ECG showed ventricular tachycardia (VT)(Figure 2B); however, serum electrolytes, calcium, magnesium, and phosphorus levels were within reference range. Aggressive resuscitative measures including multiple attempts at cardioversion with up to 200 J (biphasic) and intravenous amiodarone infusion failed to revive the patient, and he died.

Proinflammatory cytokines such as IL-6 and tumor necrosis factor α are increased in young people with ventricular arrhythmias who have no evidence of myocardial injury (MI), suggesting an inflammatory background is involved.¹ Psoriasis, a common immune-mediated inflammatory disease, has a chronic state of systemic inflammation with notably higher serum levels of tumor necrosis factor α, IFN-γ, IL-6, IL-8, IL-12, and IL-18 compared to controls.² This inflammation is not confined to skin but can involve blood vessels, joints, and the liver, as demonstrated by increased fluorodeoxyglucose uptake.³ It also seems to exert its influence on supraventricular beat development in patients with psoriasis who do not have a history of CVEs.⁴ Tumor necrosis factor α is one of the major cytokines playing a role in the inflammatory process of psoriasis. Studies have shown serum levels of tumor necrosis factor α to correlate with the clinical symptoms of heart failure and to supraventricular arrhythmia in animal models.⁴ Various extreme CVEs can be an expression of this ongoing dynamic process. It would be interesting to know which specific factors among these inflammatory cytokines lead to rhythm irregularities.

Another theory is that young patients may experience micro-MI during the disease course. These small infarcted areas may act as aberrant pulse generators or lead to conduction disturbances. One study found increased correct QT interval dispersion, a predictor of ventricular arrhythmias, to be associated with psoriasis.⁵ A nationwide population-based matched cohort study by Chiu et al⁶ revealed that patients with psoriasis have a higher risk for arrhythmia independent of traditional cardiovascular risk factors. Our patient also had severe unstable psoriasis for 8 years that may have led to increased accumulation of proarrhythmogenic cytokines in the heart and could have led to VT.

Acitretin as a potential cause of sudden cardiac death remains a possibility in our case; however, the exact mechanism leading to such sudden arrhythmia is lacking. Acitretin is known to increase serum triglycerides and cholesterol, specifically by shifting high-density lipoproteins to low-density lipoproteins, thereby increasing the risk for CVE. However, it takes time for such derangement to occur, eventually leading to CVE. Mittal et al⁷ reported a psoriasis patient who died secondary to MI after 5 days of low-dose acitretin. Lack of evidence makes acitretin a less likely cause of mortality.

We present a case of sudden cardiac death secondary to VT in a young patient with psoriasis and no other traditional cardiovascular risk factors. This case highlights the importance of being vigilant for adverse CVEs such as arrhythmia in psoriatic patients, especially in younger patients with severe unstable disease.

To the Editor:

The evolution in the understanding of psoriasis and psoriatic arthritis has unfolded many new facets of this immune-mediated inflammatory disease. Once considered to be just a cutaneous disease, psoriasis is not actually confined to skin but can involve almost any other system of the body. Cardiovascular morbidity and mortality are the major concerns in patients with psoriasis. We report the sudden death of a young man with severe psoriasis.

A 31-year-old man was admitted for severe psoriasis with pustular exacerbation (Figures 1A and 1B). He had moderate to severe unstable disease during the last 8 years and was managed with oral methotrexate (0.3–0.5 mg/kg/wk). He was not compliant with treatment, which led to multiple relapses. There was no personal or family history of risk factors for cardiovascular events (CVEs). At the time of present hospitalization, his vital parameters were normal. Physical examination revealed erythematous scaly plaques on more than 75% of the body surface area. Multiple pustules also were noted, often coalescing to form plaques (Figure 1C). Baseline investigations consisting of complete blood cell count, lipid profile, liver and renal functions, and chest radiography were within reference range. Baseline electrocardiogram (ECG) at admission was unremarkable (Figure 2A), except for sinus tachycardia. Low-voltage complexes in limb leads were appreciated as well as a corrected QT interval of 420 milliseconds (within reference range). Echocardiography was normal (visual ejection fraction of 60%).

The patient was unable to tolerate methotrexate due to excessive nausea; he was started on oral acitretin 25 mg once daily. There was no improvement in psoriasis over the following week, and he reported mild upper abdominal discomfort. He did not have any chest pain or dyspnea, and his pulse and blood pressure were normal. Serum electrolytes, liver function, lipid profile, and an ultrasound of the abdomen revealed no abnormalities. A repeat ECG showed no changes, and cardiac biomarkers were not elevated. Two days later, the patient collapsed while still in the hospital. A cardiac monitor and ECG showed ventricular tachycardia (VT)(Figure 2B); however, serum electrolytes, calcium, magnesium, and phosphorus levels were within reference range. Aggressive resuscitative measures including multiple attempts at cardioversion with up to 200 J (biphasic) and intravenous amiodarone infusion failed to revive the patient, and he died.

Proinflammatory cytokines such as IL-6 and tumor necrosis factor α are increased in young people with ventricular arrhythmias who have no evidence of myocardial injury (MI), suggesting an inflammatory background is involved.¹ Psoriasis, a common immune-mediated inflammatory disease, has a chronic state of systemic inflammation with notably higher serum levels of tumor necrosis factor α, IFN-γ, IL-6, IL-8, IL-12, and IL-18 compared to controls.² This inflammation is not confined to skin but can involve blood vessels, joints, and the liver, as demonstrated by increased fluorodeoxyglucose uptake.³ It also seems to exert its influence on supraventricular beat development in patients with psoriasis who do not have a history of CVEs.⁴ Tumor necrosis factor α is one of the major cytokines playing a role in the inflammatory process of psoriasis. Studies have shown serum levels of tumor necrosis factor α to correlate with the clinical symptoms of heart failure and to supraventricular arrhythmia in animal models.⁴ Various extreme CVEs can be an expression of this ongoing dynamic process. It would be interesting to know which specific factors among these inflammatory cytokines lead to rhythm irregularities.

Another theory is that young patients may experience micro-MI during the disease course. These small infarcted areas may act as aberrant pulse generators or lead to conduction disturbances. One study found increased correct QT interval dispersion, a predictor of ventricular arrhythmias, to be associated with psoriasis.⁵ A nationwide population-based matched cohort study by Chiu et al⁶ revealed that patients with psoriasis have a higher risk for arrhythmia independent of traditional cardiovascular risk factors. Our patient also had severe unstable psoriasis for 8 years that may have led to increased accumulation of proarrhythmogenic cytokines in the heart and could have led to VT.

Acitretin as a potential cause of sudden cardiac death remains a possibility in our case; however, the exact mechanism leading to such sudden arrhythmia is lacking. Acitretin is known to increase serum triglycerides and cholesterol, specifically by shifting high-density lipoproteins to low-density lipoproteins, thereby increasing the risk for CVE. However, it takes time for such derangement to occur, eventually leading to CVE. Mittal et al⁷ reported a psoriasis patient who died secondary to MI after 5 days of low-dose acitretin. Lack of evidence makes acitretin a less likely cause of mortality.

We present a case of sudden cardiac death secondary to VT in a young patient with psoriasis and no other traditional cardiovascular risk factors. This case highlights the importance of being vigilant for adverse CVEs such as arrhythmia in psoriatic patients, especially in younger patients with severe unstable disease.