Psoriasis

Spesolimab, a humanized, anti–interleukin-36 receptor monoclonal antibody, was associated with rapid improvement in pustules during flares, in a phase 2 study of 53 adults with generalized pustular psoriasis (GPP).

GPP is a life-threatening skin condition involving the widespread eruption of sterile pustules, with a clinical course that “can be relapsing with recurrent flares or persistent with intermittent flares,” Hervé Bachelez, MD, of the Université de Paris and coauthors wrote. GPP patients are often hospitalized, and mortality ranges from 2% to 16% from causes that include sepsis and cardiorespiratory failure.

“The role of the interleukin-36 pathway in GPP is supported by the finding of loss-of-function mutations in the interleukin-36 receptor antagonist gene (IL36RN) and associated genes (CARD14, AP1S3, SERPINA3, and MPO) and by the overexpression of interleukin-36 cytokines in GPP skin lesions,” therefore, IL-36 is a potential treatment target to manage flares, they explained.

In the multicenter, double-blind trial, published in the New England Journal of Medicine, the researchers randomized 35 adults with GPP flares to a single 900-mg intravenous dose of spesolimab and 18 to placebo. Patients in both groups could receive an open-label dose of spesolimab after day 8; all patients were followed for 12 weeks.

The primary study endpoint was the Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) pustulation subscore of 0 at 1 week after treatment. The GPPGA ranges from 0 (no visible pustules) to 4 (severe pustules). At baseline, 46% spesolimab patients and 39% placebo patients had a GPPGA pustulation subscore of 3, and 37% and 33%, respectively, had a pustulation subscore of 4.

After 1 week, 54% of the spesolimab patients had no visible pustules, compared with 6% of placebo patients; the difference was statistically significant (P < .001). The main secondary endpoint was a score of 0 or 1 (clear or almost clear skin) on the GPPGA total score after 1 week. Significantly more spesolimab patients had GPPGA total scores of 0 or 1, compared with placebo patients (43% vs. 11%, respectively; P = .02).

Overall, 6 of 35 spesolimab patients (17%) and 6% of those in the placebo groups developed infections during the first week, and 24 of 51 patients (47%) who had received spesolimab at any point during the study developed infections by week 12. Infections included urinary tract infections (three cases), influenza (three), otitis externa (two), folliculitis (two), upper respiratory tract infection (two), and pustule (two).

In the first week, 6% of spesolimab patients and none of the placebo patients reported serious adverse events; at week 12, 12% of patients who had received at least one spesolimab dose reported a serious adverse event. In addition, antidrug antibodies were identified in 23 (46%) of the 50 patients who received at least one dose of spesolimab.

“Symptoms that were observed in two patients who received spesolimab were reported as a drug reaction with eosinophilia and systemic symptoms (DRESS),” the authors noted. One patient had a RegiSCAR (European Registry of Severe Cutaneous Adverse Reactions) score and the other had a score of 3; a score below 2 indicates no DRESS, and a score of 2 or 3 indicates “possible DRESS,” they added.

“Because 15 of the 18 patients who were assigned to the placebo group received open-label spesolimab, the effect of spesolimab as compared with that of placebo could not be determined after week 1,” the researchers noted.

The study findings were limited by several factors including the short randomization period and small study population, the researchers noted. However, the effect sizes for both the primary and secondary endpoints were large, which strengthened the results.

The results support data from previous studies suggesting a role for IL-36 in the pathogenesis of GPP, and support the need for longer and larger studies of the safety and effectiveness of spesolimab for GPP patients, they concluded.

No FDA-approved therapy

“GPP is a very rare but devastating life-threatening disease that presents with the sudden onset of pustules throughout the skin,” Joel Gelfand, MD, professor of dermatology and director of the psoriasis and phototherapy center at the University of Pennsylvania, Philadelphia, said in an interview. “Without rapid treatment, GPP can result in death. Currently there are no [Food and Drug Administration]–approved treatments for this orphan disease.”

Dr. Gelfand said he was surprised by the degree of efficacy and the speed of the patient response to spesolimab, compared with placebo, which he described as “truly remarkable.” Based on the current study results, “spesolimab offers a tremendous step forward for our patients,” he added. 

Looking ahead, Dr. Gelfand noted that “longer-term studies with a comparator, such as a biologic that targets IL-17, would be helpful to more fully understand the safety, efficacy, and role that spesolimab will have in real-world patients.”

On Dec. 15, Boehringer Ingelheim announced that the FDA had granted priority review for spesolimab for treating GPP flares.

The study was supported by Boehringer Ingelheim. Lead author Dr. Bachelez had no financial conflicts to disclose. Several authors are employees of Boehringer Ingelheim. Dr. Gelfand is a consultant for the study sponsor Boehringer Ingelheim and has received research grants from Boehringer Ingelheim to his institution to support an investigator-initiated study. He also disclosed serving as a consultant and receiving research grants from other manufacturers of psoriasis products.

Spesolimab, a humanized, anti–interleukin-36 receptor monoclonal antibody, was associated with rapid improvement in pustules during flares, in a phase 2 study of 53 adults with generalized pustular psoriasis (GPP).

GPP is a life-threatening skin condition involving the widespread eruption of sterile pustules, with a clinical course that “can be relapsing with recurrent flares or persistent with intermittent flares,” Hervé Bachelez, MD, of the Université de Paris and coauthors wrote. GPP patients are often hospitalized, and mortality ranges from 2% to 16% from causes that include sepsis and cardiorespiratory failure.

“The role of the interleukin-36 pathway in GPP is supported by the finding of loss-of-function mutations in the interleukin-36 receptor antagonist gene (IL36RN) and associated genes (CARD14, AP1S3, SERPINA3, and MPO) and by the overexpression of interleukin-36 cytokines in GPP skin lesions,” therefore, IL-36 is a potential treatment target to manage flares, they explained.

In the multicenter, double-blind trial, published in the New England Journal of Medicine, the researchers randomized 35 adults with GPP flares to a single 900-mg intravenous dose of spesolimab and 18 to placebo. Patients in both groups could receive an open-label dose of spesolimab after day 8; all patients were followed for 12 weeks.

The primary study endpoint was the Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) pustulation subscore of 0 at 1 week after treatment. The GPPGA ranges from 0 (no visible pustules) to 4 (severe pustules). At baseline, 46% spesolimab patients and 39% placebo patients had a GPPGA pustulation subscore of 3, and 37% and 33%, respectively, had a pustulation subscore of 4.

After 1 week, 54% of the spesolimab patients had no visible pustules, compared with 6% of placebo patients; the difference was statistically significant (P < .001). The main secondary endpoint was a score of 0 or 1 (clear or almost clear skin) on the GPPGA total score after 1 week. Significantly more spesolimab patients had GPPGA total scores of 0 or 1, compared with placebo patients (43% vs. 11%, respectively; P = .02).

Overall, 6 of 35 spesolimab patients (17%) and 6% of those in the placebo groups developed infections during the first week, and 24 of 51 patients (47%) who had received spesolimab at any point during the study developed infections by week 12. Infections included urinary tract infections (three cases), influenza (three), otitis externa (two), folliculitis (two), upper respiratory tract infection (two), and pustule (two).

In the first week, 6% of spesolimab patients and none of the placebo patients reported serious adverse events; at week 12, 12% of patients who had received at least one spesolimab dose reported a serious adverse event. In addition, antidrug antibodies were identified in 23 (46%) of the 50 patients who received at least one dose of spesolimab.

“Symptoms that were observed in two patients who received spesolimab were reported as a drug reaction with eosinophilia and systemic symptoms (DRESS),” the authors noted. One patient had a RegiSCAR (European Registry of Severe Cutaneous Adverse Reactions) score and the other had a score of 3; a score below 2 indicates no DRESS, and a score of 2 or 3 indicates “possible DRESS,” they added.

“Because 15 of the 18 patients who were assigned to the placebo group received open-label spesolimab, the effect of spesolimab as compared with that of placebo could not be determined after week 1,” the researchers noted.

The study findings were limited by several factors including the short randomization period and small study population, the researchers noted. However, the effect sizes for both the primary and secondary endpoints were large, which strengthened the results.

The results support data from previous studies suggesting a role for IL-36 in the pathogenesis of GPP, and support the need for longer and larger studies of the safety and effectiveness of spesolimab for GPP patients, they concluded.

No FDA-approved therapy

“GPP is a very rare but devastating life-threatening disease that presents with the sudden onset of pustules throughout the skin,” Joel Gelfand, MD, professor of dermatology and director of the psoriasis and phototherapy center at the University of Pennsylvania, Philadelphia, said in an interview. “Without rapid treatment, GPP can result in death. Currently there are no [Food and Drug Administration]–approved treatments for this orphan disease.”

Dr. Gelfand said he was surprised by the degree of efficacy and the speed of the patient response to spesolimab, compared with placebo, which he described as “truly remarkable.” Based on the current study results, “spesolimab offers a tremendous step forward for our patients,” he added. 

Looking ahead, Dr. Gelfand noted that “longer-term studies with a comparator, such as a biologic that targets IL-17, would be helpful to more fully understand the safety, efficacy, and role that spesolimab will have in real-world patients.”

On Dec. 15, Boehringer Ingelheim announced that the FDA had granted priority review for spesolimab for treating GPP flares.

The study was supported by Boehringer Ingelheim. Lead author Dr. Bachelez had no financial conflicts to disclose. Several authors are employees of Boehringer Ingelheim. Dr. Gelfand is a consultant for the study sponsor Boehringer Ingelheim and has received research grants from Boehringer Ingelheim to his institution to support an investigator-initiated study. He also disclosed serving as a consultant and receiving research grants from other manufacturers of psoriasis products.

Spesolimab, a humanized, anti–interleukin-36 receptor monoclonal antibody, was associated with rapid improvement in pustules during flares, in a phase 2 study of 53 adults with generalized pustular psoriasis (GPP).

GPP is a life-threatening skin condition involving the widespread eruption of sterile pustules, with a clinical course that “can be relapsing with recurrent flares or persistent with intermittent flares,” Hervé Bachelez, MD, of the Université de Paris and coauthors wrote. GPP patients are often hospitalized, and mortality ranges from 2% to 16% from causes that include sepsis and cardiorespiratory failure.

“The role of the interleukin-36 pathway in GPP is supported by the finding of loss-of-function mutations in the interleukin-36 receptor antagonist gene (IL36RN) and associated genes (CARD14, AP1S3, SERPINA3, and MPO) and by the overexpression of interleukin-36 cytokines in GPP skin lesions,” therefore, IL-36 is a potential treatment target to manage flares, they explained.

In the multicenter, double-blind trial, published in the New England Journal of Medicine, the researchers randomized 35 adults with GPP flares to a single 900-mg intravenous dose of spesolimab and 18 to placebo. Patients in both groups could receive an open-label dose of spesolimab after day 8; all patients were followed for 12 weeks.

The primary study endpoint was the Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) pustulation subscore of 0 at 1 week after treatment. The GPPGA ranges from 0 (no visible pustules) to 4 (severe pustules). At baseline, 46% spesolimab patients and 39% placebo patients had a GPPGA pustulation subscore of 3, and 37% and 33%, respectively, had a pustulation subscore of 4.

After 1 week, 54% of the spesolimab patients had no visible pustules, compared with 6% of placebo patients; the difference was statistically significant (P < .001). The main secondary endpoint was a score of 0 or 1 (clear or almost clear skin) on the GPPGA total score after 1 week. Significantly more spesolimab patients had GPPGA total scores of 0 or 1, compared with placebo patients (43% vs. 11%, respectively; P = .02).

Overall, 6 of 35 spesolimab patients (17%) and 6% of those in the placebo groups developed infections during the first week, and 24 of 51 patients (47%) who had received spesolimab at any point during the study developed infections by week 12. Infections included urinary tract infections (three cases), influenza (three), otitis externa (two), folliculitis (two), upper respiratory tract infection (two), and pustule (two).

In the first week, 6% of spesolimab patients and none of the placebo patients reported serious adverse events; at week 12, 12% of patients who had received at least one spesolimab dose reported a serious adverse event. In addition, antidrug antibodies were identified in 23 (46%) of the 50 patients who received at least one dose of spesolimab.

“Symptoms that were observed in two patients who received spesolimab were reported as a drug reaction with eosinophilia and systemic symptoms (DRESS),” the authors noted. One patient had a RegiSCAR (European Registry of Severe Cutaneous Adverse Reactions) score and the other had a score of 3; a score below 2 indicates no DRESS, and a score of 2 or 3 indicates “possible DRESS,” they added.

“Because 15 of the 18 patients who were assigned to the placebo group received open-label spesolimab, the effect of spesolimab as compared with that of placebo could not be determined after week 1,” the researchers noted.

The study findings were limited by several factors including the short randomization period and small study population, the researchers noted. However, the effect sizes for both the primary and secondary endpoints were large, which strengthened the results.

The results support data from previous studies suggesting a role for IL-36 in the pathogenesis of GPP, and support the need for longer and larger studies of the safety and effectiveness of spesolimab for GPP patients, they concluded.

No FDA-approved therapy

“GPP is a very rare but devastating life-threatening disease that presents with the sudden onset of pustules throughout the skin,” Joel Gelfand, MD, professor of dermatology and director of the psoriasis and phototherapy center at the University of Pennsylvania, Philadelphia, said in an interview. “Without rapid treatment, GPP can result in death. Currently there are no [Food and Drug Administration]–approved treatments for this orphan disease.”

Dr. Gelfand said he was surprised by the degree of efficacy and the speed of the patient response to spesolimab, compared with placebo, which he described as “truly remarkable.” Based on the current study results, “spesolimab offers a tremendous step forward for our patients,” he added. 

Looking ahead, Dr. Gelfand noted that “longer-term studies with a comparator, such as a biologic that targets IL-17, would be helpful to more fully understand the safety, efficacy, and role that spesolimab will have in real-world patients.”

On Dec. 15, Boehringer Ingelheim announced that the FDA had granted priority review for spesolimab for treating GPP flares.

The study was supported by Boehringer Ingelheim. Lead author Dr. Bachelez had no financial conflicts to disclose. Several authors are employees of Boehringer Ingelheim. Dr. Gelfand is a consultant for the study sponsor Boehringer Ingelheim and has received research grants from Boehringer Ingelheim to his institution to support an investigator-initiated study. He also disclosed serving as a consultant and receiving research grants from other manufacturers of psoriasis products.

The Food and Drug Administration has accepted a Biologics License Application for spesolimab, a selective antibody that blocks interleukin-36 receptors, for the treatment of flares in patients with generalized pustular psoriasis, according to a statement from manufacturer Boehringer Ingelheim. The FDA also granted Priority Review to spesolimab. Priority Review is a designation granted to medications that would offer significant improvement over the currently available treatments.

Generalized pustular psoriasis (GPP), though rare, is a potentially life-threatening condition that is distinct from plaque psoriasis. Throughout the course of the disease, which is caused by the accumulation of neutrophils in the skin, patients may experience persistent disease with intermittent flares or relapsing disease with recurrent flares. The neutrophil accumulation results in the eruption of sterile, yet painful pustules across all parts of the body.

“While the severity of GPP flares can vary, if left untreated they can be life threatening due to complications such as sepsis and multisystem organ failure,” and have a significant impact on quality of life, according to the company statement.

The FDA also has granted spesolimab an Orphan Drug Designation for the treatment of GPP, and a Breakthrough Therapy Designation for the treatment of GPP flares in adults.

A marketing authorization application for spesolimab for the treatment of GPP was accepted for evaluation by the European Medicines Agency in October 2021, according to a company press release issued at that time.

A protocol for a phase 2 study of spesolimab versus placebo for treating acute flares in GPP patients was published in October in BMJ Open, after a phase 1 proof-of-concept study published in 2019 showed the potential of an IL-36 receptor antagonist to improve disease scores in adults with GPP.

More information is available on the Boehringer Ingelheim website.

dermnews@mdedge.com

The Food and Drug Administration has accepted a Biologics License Application for spesolimab, a selective antibody that blocks interleukin-36 receptors, for the treatment of flares in patients with generalized pustular psoriasis, according to a statement from manufacturer Boehringer Ingelheim. The FDA also granted Priority Review to spesolimab. Priority Review is a designation granted to medications that would offer significant improvement over the currently available treatments.

Generalized pustular psoriasis (GPP), though rare, is a potentially life-threatening condition that is distinct from plaque psoriasis. Throughout the course of the disease, which is caused by the accumulation of neutrophils in the skin, patients may experience persistent disease with intermittent flares or relapsing disease with recurrent flares. The neutrophil accumulation results in the eruption of sterile, yet painful pustules across all parts of the body.

“While the severity of GPP flares can vary, if left untreated they can be life threatening due to complications such as sepsis and multisystem organ failure,” and have a significant impact on quality of life, according to the company statement.

The FDA also has granted spesolimab an Orphan Drug Designation for the treatment of GPP, and a Breakthrough Therapy Designation for the treatment of GPP flares in adults.

A marketing authorization application for spesolimab for the treatment of GPP was accepted for evaluation by the European Medicines Agency in October 2021, according to a company press release issued at that time.

A protocol for a phase 2 study of spesolimab versus placebo for treating acute flares in GPP patients was published in October in BMJ Open, after a phase 1 proof-of-concept study published in 2019 showed the potential of an IL-36 receptor antagonist to improve disease scores in adults with GPP.

More information is available on the Boehringer Ingelheim website.

dermnews@mdedge.com

The Food and Drug Administration has accepted a Biologics License Application for spesolimab, a selective antibody that blocks interleukin-36 receptors, for the treatment of flares in patients with generalized pustular psoriasis, according to a statement from manufacturer Boehringer Ingelheim. The FDA also granted Priority Review to spesolimab. Priority Review is a designation granted to medications that would offer significant improvement over the currently available treatments.

Generalized pustular psoriasis (GPP), though rare, is a potentially life-threatening condition that is distinct from plaque psoriasis. Throughout the course of the disease, which is caused by the accumulation of neutrophils in the skin, patients may experience persistent disease with intermittent flares or relapsing disease with recurrent flares. The neutrophil accumulation results in the eruption of sterile, yet painful pustules across all parts of the body.

“While the severity of GPP flares can vary, if left untreated they can be life threatening due to complications such as sepsis and multisystem organ failure,” and have a significant impact on quality of life, according to the company statement.

The FDA also has granted spesolimab an Orphan Drug Designation for the treatment of GPP, and a Breakthrough Therapy Designation for the treatment of GPP flares in adults.

A marketing authorization application for spesolimab for the treatment of GPP was accepted for evaluation by the European Medicines Agency in October 2021, according to a company press release issued at that time.

A protocol for a phase 2 study of spesolimab versus placebo for treating acute flares in GPP patients was published in October in BMJ Open, after a phase 1 proof-of-concept study published in 2019 showed the potential of an IL-36 receptor antagonist to improve disease scores in adults with GPP.

More information is available on the Boehringer Ingelheim website.

dermnews@mdedge.com

A new study has established guselkumab (Tremfya) as both a safe and effective treatment option for psoriatic arthritis (PsA) in patients who had previously responded poorly to tumor necrosis factor inhibitors (TNFis).

“While the positive guselkumab benefit-risk profile observed through week 24 was maintained through 1 year, real-world evidence will further inform long-term guselkumab persistence in TNFi-inadequate response patients,” writes Laura C. Coates, MBChB, PhD, of the University of Oxford (England), and her coauthors. The study was published in the Annals of the Rheumatic Diseases.

Previous studies indicated that the anti–interleukin-23p19 monoclonal antibody improved outcomes in patients with PsA, even after 1 year, but some uncertainty remained regarding the surprisingly similar level of effectiveness in biologic-naive and TNFi-treated patients. Guselkumab is approved for treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy and adults with active psoriatic arthritis.

Clarity on guselkumab’s effectiveness in certain patients

“In previous studies that cemented guselkumab as a treatment option for PsA, what was odd was that the results were pretty comparable,” Eric M. Ruderman, MD, professor of medicine and associate chief for clinical affairs in the division of rheumatology at Northwestern University in Chicago, Illinois, said in an interview. “We didn’t really have a sense of how well it worked in patients who had failed other biologics, which is where you might expect a drug with a new mechanism to be used when it comes into a particular disease category.

“Not surprisingly, in this study, the overall response rate was a little less than the response rate in the other two trials,” said Dr. Ruderman, who was not involved in the study. “You can’t really compare across studies, but it does fit with what we might expect: People who’ve previously failed a TNF inhibitor might be a little less likely to respond to guselkumab, compared to someone who hasn’t seen a TNF inhibitor.”

When asked about potential follow-up studies, Dr. Ruderman noted that “the missing piece of the puzzle is that we still really have no way to compare this to other biologics. The next step would be to ask, in a single trial, what happens if you give some people TNF inhibitors and some people guselkumab? Just to try to give us context. Is this equivalent? Is it less effective? More effective? Where does it fit? Without that information, rheumatologists may struggle to figure out who is the right person for this drug and how often should they use it.”

Study details

To assess the efficacy and safety of guselkumab in patients who had previously taken TNFis but stopped because of inefficacy or intolerance, the researchers launched a randomized, double-blind study called COSMOS at 84 European sites from March 2019 to November 2020. The study’s 285 patients – 52% of whom were women, with an average overall age of 49 – were assigned to two groups: guselkumab (n = 189) or placebo (n = 96). A total of 88% of all patients had used one TNFi prior; 12% had used two.

The guselkumab group received 100-mg injections at week 0, week 4, and then every 8 weeks through week 44; the placebo group received injections at weeks 0, 4, 12, and 20, followed by 100 mg of guselkumab at weeks 24, 28, 36, and 44. Patients with less than 5% improvement from baseline in both tender and swollen joint counts at week 16 qualified for early escape to “initiate or increase the dose of one permitted concomitant medication up to the maximum allowed dose at the physician’s discretion.” Ultimately, 88% of patients in the guselkumab arm and 83% of the placebo arm completed the study.

At 24 weeks, more than 44% of the guselkumab group achieved a 20% or greater improvement in American College of Rheumatology criteria (ACR20), compared with just under 20% of the placebo group, a difference of nearly 25% (95% confidence interval, 14.1%-35.2%; multiplicity-adjusted P < .001). At 48 weeks, nearly 58% of the guselkumab group had achieved ACR20; of the 51 patients in the placebo arm who started taking guselkumab at week 24, 55% achieved ACR20 by week 48.

Through 24 weeks, 80 patients in the guselkumab group (42%) and 46 patients in the placebo group (48%) experienced adverse events; only 3.7% and 3.1% developed serious adverse events, respectively. The most common adverse events in the guselkumab group at that point included nasopharyngitis (5%) and upper respiratory tract infection (4%), which occurred at a similar frequency (5% and 3%) in the placebo group.

The authors acknowledge their study’s limitations, including imbalances in baseline characteristics such as gender and weight, as well as the COSMOS study being restricted to European patients and thus potentially limiting diversity. In addition, while the COVID-19 pandemic may have increased major protocol deviations near the end of the study, the authors note that “most were related to timing of study visits and did not impact efficacy.”

The study was funded by Janssen, and six authors reported being employees of the company. The authors also acknowledge numerous potential conflicts of interest, including receiving consulting fees and research grants from various pharmaceutical companies, including Janssen. Dr. Ruderman is a consultant for AbbVie, Bristol-Myers Squibb, Eli Lilly, Novartis, Pfizer, and Janssen and served on the data safety monitoring committee for two other phase 3 guselkumab trials.

A version of this article first appeared on Medscape.com.

A new study has established guselkumab (Tremfya) as both a safe and effective treatment option for psoriatic arthritis (PsA) in patients who had previously responded poorly to tumor necrosis factor inhibitors (TNFis).

“While the positive guselkumab benefit-risk profile observed through week 24 was maintained through 1 year, real-world evidence will further inform long-term guselkumab persistence in TNFi-inadequate response patients,” writes Laura C. Coates, MBChB, PhD, of the University of Oxford (England), and her coauthors. The study was published in the Annals of the Rheumatic Diseases.

Previous studies indicated that the anti–interleukin-23p19 monoclonal antibody improved outcomes in patients with PsA, even after 1 year, but some uncertainty remained regarding the surprisingly similar level of effectiveness in biologic-naive and TNFi-treated patients. Guselkumab is approved for treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy and adults with active psoriatic arthritis.

Clarity on guselkumab’s effectiveness in certain patients

“In previous studies that cemented guselkumab as a treatment option for PsA, what was odd was that the results were pretty comparable,” Eric M. Ruderman, MD, professor of medicine and associate chief for clinical affairs in the division of rheumatology at Northwestern University in Chicago, Illinois, said in an interview. “We didn’t really have a sense of how well it worked in patients who had failed other biologics, which is where you might expect a drug with a new mechanism to be used when it comes into a particular disease category.

“Not surprisingly, in this study, the overall response rate was a little less than the response rate in the other two trials,” said Dr. Ruderman, who was not involved in the study. “You can’t really compare across studies, but it does fit with what we might expect: People who’ve previously failed a TNF inhibitor might be a little less likely to respond to guselkumab, compared to someone who hasn’t seen a TNF inhibitor.”

When asked about potential follow-up studies, Dr. Ruderman noted that “the missing piece of the puzzle is that we still really have no way to compare this to other biologics. The next step would be to ask, in a single trial, what happens if you give some people TNF inhibitors and some people guselkumab? Just to try to give us context. Is this equivalent? Is it less effective? More effective? Where does it fit? Without that information, rheumatologists may struggle to figure out who is the right person for this drug and how often should they use it.”

Study details

To assess the efficacy and safety of guselkumab in patients who had previously taken TNFis but stopped because of inefficacy or intolerance, the researchers launched a randomized, double-blind study called COSMOS at 84 European sites from March 2019 to November 2020. The study’s 285 patients – 52% of whom were women, with an average overall age of 49 – were assigned to two groups: guselkumab (n = 189) or placebo (n = 96). A total of 88% of all patients had used one TNFi prior; 12% had used two.

The guselkumab group received 100-mg injections at week 0, week 4, and then every 8 weeks through week 44; the placebo group received injections at weeks 0, 4, 12, and 20, followed by 100 mg of guselkumab at weeks 24, 28, 36, and 44. Patients with less than 5% improvement from baseline in both tender and swollen joint counts at week 16 qualified for early escape to “initiate or increase the dose of one permitted concomitant medication up to the maximum allowed dose at the physician’s discretion.” Ultimately, 88% of patients in the guselkumab arm and 83% of the placebo arm completed the study.

At 24 weeks, more than 44% of the guselkumab group achieved a 20% or greater improvement in American College of Rheumatology criteria (ACR20), compared with just under 20% of the placebo group, a difference of nearly 25% (95% confidence interval, 14.1%-35.2%; multiplicity-adjusted P < .001). At 48 weeks, nearly 58% of the guselkumab group had achieved ACR20; of the 51 patients in the placebo arm who started taking guselkumab at week 24, 55% achieved ACR20 by week 48.

Through 24 weeks, 80 patients in the guselkumab group (42%) and 46 patients in the placebo group (48%) experienced adverse events; only 3.7% and 3.1% developed serious adverse events, respectively. The most common adverse events in the guselkumab group at that point included nasopharyngitis (5%) and upper respiratory tract infection (4%), which occurred at a similar frequency (5% and 3%) in the placebo group.

The authors acknowledge their study’s limitations, including imbalances in baseline characteristics such as gender and weight, as well as the COSMOS study being restricted to European patients and thus potentially limiting diversity. In addition, while the COVID-19 pandemic may have increased major protocol deviations near the end of the study, the authors note that “most were related to timing of study visits and did not impact efficacy.”

The study was funded by Janssen, and six authors reported being employees of the company. The authors also acknowledge numerous potential conflicts of interest, including receiving consulting fees and research grants from various pharmaceutical companies, including Janssen. Dr. Ruderman is a consultant for AbbVie, Bristol-Myers Squibb, Eli Lilly, Novartis, Pfizer, and Janssen and served on the data safety monitoring committee for two other phase 3 guselkumab trials.

A version of this article first appeared on Medscape.com.

A new study has established guselkumab (Tremfya) as both a safe and effective treatment option for psoriatic arthritis (PsA) in patients who had previously responded poorly to tumor necrosis factor inhibitors (TNFis).

“While the positive guselkumab benefit-risk profile observed through week 24 was maintained through 1 year, real-world evidence will further inform long-term guselkumab persistence in TNFi-inadequate response patients,” writes Laura C. Coates, MBChB, PhD, of the University of Oxford (England), and her coauthors. The study was published in the Annals of the Rheumatic Diseases.

Previous studies indicated that the anti–interleukin-23p19 monoclonal antibody improved outcomes in patients with PsA, even after 1 year, but some uncertainty remained regarding the surprisingly similar level of effectiveness in biologic-naive and TNFi-treated patients. Guselkumab is approved for treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy and adults with active psoriatic arthritis.

Clarity on guselkumab’s effectiveness in certain patients

“In previous studies that cemented guselkumab as a treatment option for PsA, what was odd was that the results were pretty comparable,” Eric M. Ruderman, MD, professor of medicine and associate chief for clinical affairs in the division of rheumatology at Northwestern University in Chicago, Illinois, said in an interview. “We didn’t really have a sense of how well it worked in patients who had failed other biologics, which is where you might expect a drug with a new mechanism to be used when it comes into a particular disease category.

“Not surprisingly, in this study, the overall response rate was a little less than the response rate in the other two trials,” said Dr. Ruderman, who was not involved in the study. “You can’t really compare across studies, but it does fit with what we might expect: People who’ve previously failed a TNF inhibitor might be a little less likely to respond to guselkumab, compared to someone who hasn’t seen a TNF inhibitor.”

When asked about potential follow-up studies, Dr. Ruderman noted that “the missing piece of the puzzle is that we still really have no way to compare this to other biologics. The next step would be to ask, in a single trial, what happens if you give some people TNF inhibitors and some people guselkumab? Just to try to give us context. Is this equivalent? Is it less effective? More effective? Where does it fit? Without that information, rheumatologists may struggle to figure out who is the right person for this drug and how often should they use it.”

Study details

To assess the efficacy and safety of guselkumab in patients who had previously taken TNFis but stopped because of inefficacy or intolerance, the researchers launched a randomized, double-blind study called COSMOS at 84 European sites from March 2019 to November 2020. The study’s 285 patients – 52% of whom were women, with an average overall age of 49 – were assigned to two groups: guselkumab (n = 189) or placebo (n = 96). A total of 88% of all patients had used one TNFi prior; 12% had used two.

The guselkumab group received 100-mg injections at week 0, week 4, and then every 8 weeks through week 44; the placebo group received injections at weeks 0, 4, 12, and 20, followed by 100 mg of guselkumab at weeks 24, 28, 36, and 44. Patients with less than 5% improvement from baseline in both tender and swollen joint counts at week 16 qualified for early escape to “initiate or increase the dose of one permitted concomitant medication up to the maximum allowed dose at the physician’s discretion.” Ultimately, 88% of patients in the guselkumab arm and 83% of the placebo arm completed the study.

At 24 weeks, more than 44% of the guselkumab group achieved a 20% or greater improvement in American College of Rheumatology criteria (ACR20), compared with just under 20% of the placebo group, a difference of nearly 25% (95% confidence interval, 14.1%-35.2%; multiplicity-adjusted P < .001). At 48 weeks, nearly 58% of the guselkumab group had achieved ACR20; of the 51 patients in the placebo arm who started taking guselkumab at week 24, 55% achieved ACR20 by week 48.

Through 24 weeks, 80 patients in the guselkumab group (42%) and 46 patients in the placebo group (48%) experienced adverse events; only 3.7% and 3.1% developed serious adverse events, respectively. The most common adverse events in the guselkumab group at that point included nasopharyngitis (5%) and upper respiratory tract infection (4%), which occurred at a similar frequency (5% and 3%) in the placebo group.

The authors acknowledge their study’s limitations, including imbalances in baseline characteristics such as gender and weight, as well as the COSMOS study being restricted to European patients and thus potentially limiting diversity. In addition, while the COVID-19 pandemic may have increased major protocol deviations near the end of the study, the authors note that “most were related to timing of study visits and did not impact efficacy.”

The study was funded by Janssen, and six authors reported being employees of the company. The authors also acknowledge numerous potential conflicts of interest, including receiving consulting fees and research grants from various pharmaceutical companies, including Janssen. Dr. Ruderman is a consultant for AbbVie, Bristol-Myers Squibb, Eli Lilly, Novartis, Pfizer, and Janssen and served on the data safety monitoring committee for two other phase 3 guselkumab trials.

A version of this article first appeared on Medscape.com.

A retrospective observational study of nearly 1200 prior biologic-experienced adult patients with psoriasis now receiving either secukinumab (n=780) or ixekizumab (n=411), both of which inhibit IL-17A, examined drug persistence after 18 months. Ixekizumab was associated with significantly higher rates of high treatment adherence (42% vs 35%; P = .019) and persistence (44.9% vs 36.9%; P = .007) and lower discontinuation (48.4% vs 56.0%; P = .018) and switching (26.6% vs 34.0%; P = .009) rates than secukinumab. Both drugs are dosed monthly after an initial loading dose (Blauvelt A et al. Dermatol Ther (Heidelb).

With several biologic options available, patients may be switched from one biologic to another if they are not having an adequate response. Separate studies have shown that patients with an inadequate response to ustekinumab are likely to have a better response when switched to brodalumab or guselkumab, although this does not tell us if one is more likely to be effective than the other. In a recent matching-adjusted indirect comparison study using data for patients with psoriasis who responded inadequately to ustekinumab and switched to receive brodalumab (n=121) or guselkumab (n=135) the authors found that brodalumab was associated with greater improvements than guselkumab in inadequate responders to ustekinumab with a PASI 100 rate at week 36 of 40.3% for brodalumab vs 20.0% for guselkumab; P < 0.001. (Hampton P et al. Psoriasis (Auckl).

While biologics have revolutionized the treatment of psoriasis, not all patients with extensive disease desire or are appropriate for a systemic therapy. Topical steroids, the most commonly used topical psoriasis therapy, still carry some risk of systemic absorption and are associate with cutaneous side effects such as atrophy with prolonged use. Tarpinarof 1% cream is a novel aryl hydrocarbon receptor modulating agent that has been shown in phase 3 studies to be an effective treatment for psoriasis when applied once a day. A recent open label study of 21 adult patients with extensive plaque psoriasis (20% or more body surface area (BSA) involvement, mean baseline BSA 27.2%) who applied tapinarof cream 1% QD daily showed that 94.7% of patients had a decrease in their PASI score (mean PASI decrease of 59.6%). Despite the large BSA being treated, tapinarof plasma concentration were low and remained below the quantification level in the majority (67.9%) of samples tested. There were also no concerning EKG changes such as QT prolongation. Folliculitis and headache were the most common adverse events (each reported by 4 patients) (Jett JE et al. Am J Clin Dermatol).

These studies all provide valuable data in helping us to make the best treatment decisions for patients with moderate to severe plaque psoriasis.

A retrospective observational study of nearly 1200 prior biologic-experienced adult patients with psoriasis now receiving either secukinumab (n=780) or ixekizumab (n=411), both of which inhibit IL-17A, examined drug persistence after 18 months. Ixekizumab was associated with significantly higher rates of high treatment adherence (42% vs 35%; P = .019) and persistence (44.9% vs 36.9%; P = .007) and lower discontinuation (48.4% vs 56.0%; P = .018) and switching (26.6% vs 34.0%; P = .009) rates than secukinumab. Both drugs are dosed monthly after an initial loading dose (Blauvelt A et al. Dermatol Ther (Heidelb).

With several biologic options available, patients may be switched from one biologic to another if they are not having an adequate response. Separate studies have shown that patients with an inadequate response to ustekinumab are likely to have a better response when switched to brodalumab or guselkumab, although this does not tell us if one is more likely to be effective than the other. In a recent matching-adjusted indirect comparison study using data for patients with psoriasis who responded inadequately to ustekinumab and switched to receive brodalumab (n=121) or guselkumab (n=135) the authors found that brodalumab was associated with greater improvements than guselkumab in inadequate responders to ustekinumab with a PASI 100 rate at week 36 of 40.3% for brodalumab vs 20.0% for guselkumab; P < 0.001. (Hampton P et al. Psoriasis (Auckl).

While biologics have revolutionized the treatment of psoriasis, not all patients with extensive disease desire or are appropriate for a systemic therapy. Topical steroids, the most commonly used topical psoriasis therapy, still carry some risk of systemic absorption and are associate with cutaneous side effects such as atrophy with prolonged use. Tarpinarof 1% cream is a novel aryl hydrocarbon receptor modulating agent that has been shown in phase 3 studies to be an effective treatment for psoriasis when applied once a day. A recent open label study of 21 adult patients with extensive plaque psoriasis (20% or more body surface area (BSA) involvement, mean baseline BSA 27.2%) who applied tapinarof cream 1% QD daily showed that 94.7% of patients had a decrease in their PASI score (mean PASI decrease of 59.6%). Despite the large BSA being treated, tapinarof plasma concentration were low and remained below the quantification level in the majority (67.9%) of samples tested. There were also no concerning EKG changes such as QT prolongation. Folliculitis and headache were the most common adverse events (each reported by 4 patients) (Jett JE et al. Am J Clin Dermatol).

These studies all provide valuable data in helping us to make the best treatment decisions for patients with moderate to severe plaque psoriasis.

A retrospective observational study of nearly 1200 prior biologic-experienced adult patients with psoriasis now receiving either secukinumab (n=780) or ixekizumab (n=411), both of which inhibit IL-17A, examined drug persistence after 18 months. Ixekizumab was associated with significantly higher rates of high treatment adherence (42% vs 35%; P = .019) and persistence (44.9% vs 36.9%; P = .007) and lower discontinuation (48.4% vs 56.0%; P = .018) and switching (26.6% vs 34.0%; P = .009) rates than secukinumab. Both drugs are dosed monthly after an initial loading dose (Blauvelt A et al. Dermatol Ther (Heidelb).

With several biologic options available, patients may be switched from one biologic to another if they are not having an adequate response. Separate studies have shown that patients with an inadequate response to ustekinumab are likely to have a better response when switched to brodalumab or guselkumab, although this does not tell us if one is more likely to be effective than the other. In a recent matching-adjusted indirect comparison study using data for patients with psoriasis who responded inadequately to ustekinumab and switched to receive brodalumab (n=121) or guselkumab (n=135) the authors found that brodalumab was associated with greater improvements than guselkumab in inadequate responders to ustekinumab with a PASI 100 rate at week 36 of 40.3% for brodalumab vs 20.0% for guselkumab; P < 0.001. (Hampton P et al. Psoriasis (Auckl).

While biologics have revolutionized the treatment of psoriasis, not all patients with extensive disease desire or are appropriate for a systemic therapy. Topical steroids, the most commonly used topical psoriasis therapy, still carry some risk of systemic absorption and are associate with cutaneous side effects such as atrophy with prolonged use. Tarpinarof 1% cream is a novel aryl hydrocarbon receptor modulating agent that has been shown in phase 3 studies to be an effective treatment for psoriasis when applied once a day. A recent open label study of 21 adult patients with extensive plaque psoriasis (20% or more body surface area (BSA) involvement, mean baseline BSA 27.2%) who applied tapinarof cream 1% QD daily showed that 94.7% of patients had a decrease in their PASI score (mean PASI decrease of 59.6%). Despite the large BSA being treated, tapinarof plasma concentration were low and remained below the quantification level in the majority (67.9%) of samples tested. There were also no concerning EKG changes such as QT prolongation. Folliculitis and headache were the most common adverse events (each reported by 4 patients) (Jett JE et al. Am J Clin Dermatol).

These studies all provide valuable data in helping us to make the best treatment decisions for patients with moderate to severe plaque psoriasis.

Key clinical point: Patients with moderate-to-severe plaque psoriasis who respond inadequately to ustekinumab should preferably be switched to brodalumab rather than guselkumab.

Major finding: Patients with an inadequate response to ustekinumab who switched to brodalumab vs guselkumab had higher Psoriasis Area Severity Index (PASI) 100 response rate at week 36 (40.3% vs 20.0%; P < .001) and PASI 90 response rate at weeks 12 (62.7% vs 48.1%; P = .002) and 36 (63.7% vs 51.1%; P = .004).

Study details: This matching-adjusted indirect comparison study employed data for patients with moderate-to-severe plaque psoriasis who responded inadequately to ustekinumab and switched to receive brodalumab (n=121) in AMAGINE-2 and -3 and or to receive guselkumab (n=135) in NAVIGATE, phase 3, trials.

Disclosures: The study was supported by LEO Pharma A/S. P Hampton and M Augustin declared receiving research/educational grants, consultation/speaker honoraria, and/or travel expenses and serving as an advisory board member or clinical trial participant for various companies, including LEO Pharma. E Borg is a current employee and JB Hansen is a former employee of LEO Pharma.

Source: Hampton P et al. Psoriasis (Auckl). 2021 Nov 3. doi: 10.2147/PTT.S326121.

Key clinical point: Patients with moderate-to-severe plaque psoriasis who respond inadequately to ustekinumab should preferably be switched to brodalumab rather than guselkumab.

Major finding: Patients with an inadequate response to ustekinumab who switched to brodalumab vs guselkumab had higher Psoriasis Area Severity Index (PASI) 100 response rate at week 36 (40.3% vs 20.0%; P < .001) and PASI 90 response rate at weeks 12 (62.7% vs 48.1%; P = .002) and 36 (63.7% vs 51.1%; P = .004).

Study details: This matching-adjusted indirect comparison study employed data for patients with moderate-to-severe plaque psoriasis who responded inadequately to ustekinumab and switched to receive brodalumab (n=121) in AMAGINE-2 and -3 and or to receive guselkumab (n=135) in NAVIGATE, phase 3, trials.

Disclosures: The study was supported by LEO Pharma A/S. P Hampton and M Augustin declared receiving research/educational grants, consultation/speaker honoraria, and/or travel expenses and serving as an advisory board member or clinical trial participant for various companies, including LEO Pharma. E Borg is a current employee and JB Hansen is a former employee of LEO Pharma.

Source: Hampton P et al. Psoriasis (Auckl). 2021 Nov 3. doi: 10.2147/PTT.S326121.

Key clinical point: Patients with moderate-to-severe plaque psoriasis who respond inadequately to ustekinumab should preferably be switched to brodalumab rather than guselkumab.

Major finding: Patients with an inadequate response to ustekinumab who switched to brodalumab vs guselkumab had higher Psoriasis Area Severity Index (PASI) 100 response rate at week 36 (40.3% vs 20.0%; P < .001) and PASI 90 response rate at weeks 12 (62.7% vs 48.1%; P = .002) and 36 (63.7% vs 51.1%; P = .004).

Study details: This matching-adjusted indirect comparison study employed data for patients with moderate-to-severe plaque psoriasis who responded inadequately to ustekinumab and switched to receive brodalumab (n=121) in AMAGINE-2 and -3 and or to receive guselkumab (n=135) in NAVIGATE, phase 3, trials.

Disclosures: The study was supported by LEO Pharma A/S. P Hampton and M Augustin declared receiving research/educational grants, consultation/speaker honoraria, and/or travel expenses and serving as an advisory board member or clinical trial participant for various companies, including LEO Pharma. E Borg is a current employee and JB Hansen is a former employee of LEO Pharma.

Source: Hampton P et al. Psoriasis (Auckl). 2021 Nov 3. doi: 10.2147/PTT.S326121.

Key clinical point: Patients with psoriasis exhibit significantly lower levels of salivary cortisol despite having higher psychological stress levels, suggesting the existence of an impaired cortisol response to stress.

Major finding: Although patients with psoriasis vs controls had a significantly higher Perceived Stress Scale score (17.2±0.6 vs 15.1±0.8; P = .0289), their salivary cortisol levels were significantly lower (9.6±0.5 vs 14.0±1.1 nmol/L; P < .001).

Study details: This was a cross-sectional study including 126 adult patients with plaque psoriasis who had not received systemic anti-psoriasis therapy since at least 6 months and 116 healthy adult controls.

Disclosures: The study was supported by Fondazione Cariplo. P Gisondi and G Girolomoni declared serving as consultants or speakers for various organizations.

Source: Gisondi P et al. J Pers Med. 2021 Oct 23. doi: 10.3390/jpm11111069.

Key clinical point: Patients with psoriasis exhibit significantly lower levels of salivary cortisol despite having higher psychological stress levels, suggesting the existence of an impaired cortisol response to stress.

Major finding: Although patients with psoriasis vs controls had a significantly higher Perceived Stress Scale score (17.2±0.6 vs 15.1±0.8; P = .0289), their salivary cortisol levels were significantly lower (9.6±0.5 vs 14.0±1.1 nmol/L; P < .001).

Study details: This was a cross-sectional study including 126 adult patients with plaque psoriasis who had not received systemic anti-psoriasis therapy since at least 6 months and 116 healthy adult controls.

Disclosures: The study was supported by Fondazione Cariplo. P Gisondi and G Girolomoni declared serving as consultants or speakers for various organizations.

Source: Gisondi P et al. J Pers Med. 2021 Oct 23. doi: 10.3390/jpm11111069.

Key clinical point: Patients with psoriasis exhibit significantly lower levels of salivary cortisol despite having higher psychological stress levels, suggesting the existence of an impaired cortisol response to stress.

Major finding: Although patients with psoriasis vs controls had a significantly higher Perceived Stress Scale score (17.2±0.6 vs 15.1±0.8; P = .0289), their salivary cortisol levels were significantly lower (9.6±0.5 vs 14.0±1.1 nmol/L; P < .001).

Study details: This was a cross-sectional study including 126 adult patients with plaque psoriasis who had not received systemic anti-psoriasis therapy since at least 6 months and 116 healthy adult controls.

Disclosures: The study was supported by Fondazione Cariplo. P Gisondi and G Girolomoni declared serving as consultants or speakers for various organizations.

Source: Gisondi P et al. J Pers Med. 2021 Oct 23. doi: 10.3390/jpm11111069.

Key clinical point: Given the chronic nature of the disease, antipsoriasis biologics are associated with low median persistence, which is relatively high for interleukin inhibitors vs tumor necrosis factor inhibitors and may change over time.

Major finding: Overall, the median persistence was 23.8 months (95% CI, 21.6-26.2), longest for ustekinumab (49.3 months [95% CI, 38.0-59.1]) and shortest for etanercept (16.3 months [95% CI, 14.5-19.0]). An approximately 50% decrease in the median persistence for ustekinumab, from 62.3 (95% CI, 45.6-∞) months to 32.7 (95% CI, 21.2-49.3) months, occurred between 2010-2011 and 2014-2016.

Study details: The data come from a retrospective cohort study consisting of 2,292 adult patients with psoriasis who had received at least 1 biologic between 2010 and 2018.

Disclosures: The study was sponsored by LEO Pharma. Levin L-Å declared receiving consulting fees from various sources including LEO Pharma, and some of the authors are employees of LEO Pharma.

Source: Schmitt-Egenolf M et al. Dermatol Ther (Heidelb). 2021 Oct 14. doi: 10.1007/s13555-021-00616-7.

Key clinical point: Given the chronic nature of the disease, antipsoriasis biologics are associated with low median persistence, which is relatively high for interleukin inhibitors vs tumor necrosis factor inhibitors and may change over time.

Major finding: Overall, the median persistence was 23.8 months (95% CI, 21.6-26.2), longest for ustekinumab (49.3 months [95% CI, 38.0-59.1]) and shortest for etanercept (16.3 months [95% CI, 14.5-19.0]). An approximately 50% decrease in the median persistence for ustekinumab, from 62.3 (95% CI, 45.6-∞) months to 32.7 (95% CI, 21.2-49.3) months, occurred between 2010-2011 and 2014-2016.

Study details: The data come from a retrospective cohort study consisting of 2,292 adult patients with psoriasis who had received at least 1 biologic between 2010 and 2018.

Disclosures: The study was sponsored by LEO Pharma. Levin L-Å declared receiving consulting fees from various sources including LEO Pharma, and some of the authors are employees of LEO Pharma.

Source: Schmitt-Egenolf M et al. Dermatol Ther (Heidelb). 2021 Oct 14. doi: 10.1007/s13555-021-00616-7.

Key clinical point: Given the chronic nature of the disease, antipsoriasis biologics are associated with low median persistence, which is relatively high for interleukin inhibitors vs tumor necrosis factor inhibitors and may change over time.

Major finding: Overall, the median persistence was 23.8 months (95% CI, 21.6-26.2), longest for ustekinumab (49.3 months [95% CI, 38.0-59.1]) and shortest for etanercept (16.3 months [95% CI, 14.5-19.0]). An approximately 50% decrease in the median persistence for ustekinumab, from 62.3 (95% CI, 45.6-∞) months to 32.7 (95% CI, 21.2-49.3) months, occurred between 2010-2011 and 2014-2016.

Study details: The data come from a retrospective cohort study consisting of 2,292 adult patients with psoriasis who had received at least 1 biologic between 2010 and 2018.

Disclosures: The study was sponsored by LEO Pharma. Levin L-Å declared receiving consulting fees from various sources including LEO Pharma, and some of the authors are employees of LEO Pharma.

Source: Schmitt-Egenolf M et al. Dermatol Ther (Heidelb). 2021 Oct 14. doi: 10.1007/s13555-021-00616-7.

Key clinical point: The biosimilar AVT02 is as efficacious, safe, and immunogenic as its originator, adalimumab, in moderate-to-severe chronic plaque psoriasis.

Major finding: At week 16, AVT02 and originator adalimumab induced comparable percentage improvement in Psoriasis Area Severity Index (91.6% and 89.6%, respectively), with the difference in percentage improvement within the predefined equivalence margins of ±10% (90% CI, −0.76 to 5.29), along with similar safety, tolerability, and immunogenicity profiles, which lasted through week 50.

Study details: This was a phase 3 study including 413 adult patients with moderate-to-severe chronic plaque psoriasis who were initially assigned to receive AVT02 or adalimumab; at week 16, the latter were randomly reassigned to continue receiving adalimumab or switch to AVT02 until week 48.

Disclosures: The study was sponsored by Alvotech Swiss AG. SR Feldman and R Kay disclosed receiving research grants, speaker honoraria, or consultancy fees from various sources, including Alvotech, and some of the authors declared being employees of Alvotech.

Source: Feldman SR et al. BioDrugs. 2021 Oct 16. doi: 10.1007/s40259-021-00502-w.

Key clinical point: The biosimilar AVT02 is as efficacious, safe, and immunogenic as its originator, adalimumab, in moderate-to-severe chronic plaque psoriasis.

Major finding: At week 16, AVT02 and originator adalimumab induced comparable percentage improvement in Psoriasis Area Severity Index (91.6% and 89.6%, respectively), with the difference in percentage improvement within the predefined equivalence margins of ±10% (90% CI, −0.76 to 5.29), along with similar safety, tolerability, and immunogenicity profiles, which lasted through week 50.

Study details: This was a phase 3 study including 413 adult patients with moderate-to-severe chronic plaque psoriasis who were initially assigned to receive AVT02 or adalimumab; at week 16, the latter were randomly reassigned to continue receiving adalimumab or switch to AVT02 until week 48.

Disclosures: The study was sponsored by Alvotech Swiss AG. SR Feldman and R Kay disclosed receiving research grants, speaker honoraria, or consultancy fees from various sources, including Alvotech, and some of the authors declared being employees of Alvotech.

Source: Feldman SR et al. BioDrugs. 2021 Oct 16. doi: 10.1007/s40259-021-00502-w.

Key clinical point: The biosimilar AVT02 is as efficacious, safe, and immunogenic as its originator, adalimumab, in moderate-to-severe chronic plaque psoriasis.

Major finding: At week 16, AVT02 and originator adalimumab induced comparable percentage improvement in Psoriasis Area Severity Index (91.6% and 89.6%, respectively), with the difference in percentage improvement within the predefined equivalence margins of ±10% (90% CI, −0.76 to 5.29), along with similar safety, tolerability, and immunogenicity profiles, which lasted through week 50.

Study details: This was a phase 3 study including 413 adult patients with moderate-to-severe chronic plaque psoriasis who were initially assigned to receive AVT02 or adalimumab; at week 16, the latter were randomly reassigned to continue receiving adalimumab or switch to AVT02 until week 48.

Disclosures: The study was sponsored by Alvotech Swiss AG. SR Feldman and R Kay disclosed receiving research grants, speaker honoraria, or consultancy fees from various sources, including Alvotech, and some of the authors declared being employees of Alvotech.

Source: Feldman SR et al. BioDrugs. 2021 Oct 16. doi: 10.1007/s40259-021-00502-w.

Key clinical point: Compared with secukinumab, ixekizumab concorded with significantly increased adherence rates and decreased nonpersistence, discontinuation, and switching in biologic-experienced patients with psoriasis.

Major finding: After 18 months of follow-up, ixekizumab was associated with significantly higher rates of high treatment adherence (42% vs 35%; P = .019) and persistence (44.9% vs 36.9%; P = .007) and lower discontinuation (48.4% vs 56.0%; P = .018) and switching (26.6% vs 34.0%; P = .009) rates than secukinumab.

Study details: Findings are from a retrospective observational study consisting of prior biologic-experienced adult patients with psoriasis now receiving either secukinumab (n=780) or ixekizumab (n=411).

Disclosures: The study was supported by Eli Lilly and Company, USA. The lead author declared serving as a scientific advisor/clinical study investigator for various companies including Eli Lilly. Some of the authors are full-time employees or stakeholders of Eli Lilly, and a few others work for an alternative employer, which received compensation from Eli Lilly.

Source: Blauvelt A et al. Dermatol Ther (Heidelb). 2021 Oct 15. doi: 10.1007/s13555-021-00627-4.

Key clinical point: Compared with secukinumab, ixekizumab concorded with significantly increased adherence rates and decreased nonpersistence, discontinuation, and switching in biologic-experienced patients with psoriasis.

Major finding: After 18 months of follow-up, ixekizumab was associated with significantly higher rates of high treatment adherence (42% vs 35%; P = .019) and persistence (44.9% vs 36.9%; P = .007) and lower discontinuation (48.4% vs 56.0%; P = .018) and switching (26.6% vs 34.0%; P = .009) rates than secukinumab.

Study details: Findings are from a retrospective observational study consisting of prior biologic-experienced adult patients with psoriasis now receiving either secukinumab (n=780) or ixekizumab (n=411).

Disclosures: The study was supported by Eli Lilly and Company, USA. The lead author declared serving as a scientific advisor/clinical study investigator for various companies including Eli Lilly. Some of the authors are full-time employees or stakeholders of Eli Lilly, and a few others work for an alternative employer, which received compensation from Eli Lilly.

Source: Blauvelt A et al. Dermatol Ther (Heidelb). 2021 Oct 15. doi: 10.1007/s13555-021-00627-4.

Key clinical point: Compared with secukinumab, ixekizumab concorded with significantly increased adherence rates and decreased nonpersistence, discontinuation, and switching in biologic-experienced patients with psoriasis.

Major finding: After 18 months of follow-up, ixekizumab was associated with significantly higher rates of high treatment adherence (42% vs 35%; P = .019) and persistence (44.9% vs 36.9%; P = .007) and lower discontinuation (48.4% vs 56.0%; P = .018) and switching (26.6% vs 34.0%; P = .009) rates than secukinumab.

Study details: Findings are from a retrospective observational study consisting of prior biologic-experienced adult patients with psoriasis now receiving either secukinumab (n=780) or ixekizumab (n=411).

Disclosures: The study was supported by Eli Lilly and Company, USA. The lead author declared serving as a scientific advisor/clinical study investigator for various companies including Eli Lilly. Some of the authors are full-time employees or stakeholders of Eli Lilly, and a few others work for an alternative employer, which received compensation from Eli Lilly.

Source: Blauvelt A et al. Dermatol Ther (Heidelb). 2021 Oct 15. doi: 10.1007/s13555-021-00627-4.

Key clinical point: Tapinarof cream 1% applied once daily (QD) displayed significant efficacy after 4 weeks along with good tolerability and limited systemic exposure in patients with extensive plaque psoriasis.

Major finding: At day 29, the mean Psoriasis Area Severity Index score changed significantly with a mean percentage change from baseline of −59.56% (95% CI, −73.53% to −45.59%) and the tapinarof plasma concentration remained below the quantification level (< 50 pg/mL) in the majority (67.9%) of patients; 17 patients reported no irritation and 2 had mild irritation at the application site.

Study details: Findings are from a phase 2a trial involving 21 adult patients with extensive plaque psoriasis (20% or more body surface area involvement) who applied tapinarof cream 1% QD for 29 days.

Disclosures: The study was supported by Dermavant Sciences, Inc. Some of the authors, including the lead author, declared serving as an employee or investigator for Dermavant Sciences, Inc.

Source: Jett JE et al. Am J Clin Dermatol. 2021 Oct 28. doi: 10.1007/s40257-021-00641-4.

Key clinical point: Tapinarof cream 1% applied once daily (QD) displayed significant efficacy after 4 weeks along with good tolerability and limited systemic exposure in patients with extensive plaque psoriasis.

Major finding: At day 29, the mean Psoriasis Area Severity Index score changed significantly with a mean percentage change from baseline of −59.56% (95% CI, −73.53% to −45.59%) and the tapinarof plasma concentration remained below the quantification level (< 50 pg/mL) in the majority (67.9%) of patients; 17 patients reported no irritation and 2 had mild irritation at the application site.

Study details: Findings are from a phase 2a trial involving 21 adult patients with extensive plaque psoriasis (20% or more body surface area involvement) who applied tapinarof cream 1% QD for 29 days.

Disclosures: The study was supported by Dermavant Sciences, Inc. Some of the authors, including the lead author, declared serving as an employee or investigator for Dermavant Sciences, Inc.

Source: Jett JE et al. Am J Clin Dermatol. 2021 Oct 28. doi: 10.1007/s40257-021-00641-4.

Key clinical point: Tapinarof cream 1% applied once daily (QD) displayed significant efficacy after 4 weeks along with good tolerability and limited systemic exposure in patients with extensive plaque psoriasis.

Major finding: At day 29, the mean Psoriasis Area Severity Index score changed significantly with a mean percentage change from baseline of −59.56% (95% CI, −73.53% to −45.59%) and the tapinarof plasma concentration remained below the quantification level (< 50 pg/mL) in the majority (67.9%) of patients; 17 patients reported no irritation and 2 had mild irritation at the application site.

Study details: Findings are from a phase 2a trial involving 21 adult patients with extensive plaque psoriasis (20% or more body surface area involvement) who applied tapinarof cream 1% QD for 29 days.

Disclosures: The study was supported by Dermavant Sciences, Inc. Some of the authors, including the lead author, declared serving as an employee or investigator for Dermavant Sciences, Inc.

Source: Jett JE et al. Am J Clin Dermatol. 2021 Oct 28. doi: 10.1007/s40257-021-00641-4.