Psoriasis

LAS VEGAS – Current major guidelines for treatment of psoriatic arthritis (PsA) shortchange the value of the anti–interleukin-17 biologics for this disease, Kenneth B. Gordon, MD, said at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.

The 2018 joint American College of Rheumatology/National Psoriasis Association guidelines recommend the anti–tumor necrosis factor agents as first-line biologic therapy for PsA, with the anti–IL-17 biologics held in reserve as second-tier therapy for when the anti-TNFs don’t work. That’s largely because the guidance was developed before the compelling evidence for the anti–IL-17 agents as the biologics of choice was appreciated, according to Dr. Gordon, professor and chair of the department of dermatology at the Medical College of Wisconsin, Milwaukee.

“Many people go by these guidelines,” the dermatologist noted. “I think it’s really critical to look at the data and not just the guidelines because the guidelines don’t give full credit to the anti–IL-17 agents,” he added.

“Emerging psoriatic arthritis data may likely put this class of medications into the forefront of treatment for patients who have both psoriasis and psoriatic arthritis because you generally get higher responses for the skin disease than with anti-TNF therapy, and with similar responses in psoriatic arthritis.”

Two IL-17 inhibitors are approved for both PsA and psoriasis: secukinumab (Cosentyx) and ixekizumab (Taltz). In addition, brodalumab (Siliq), approved for psoriasis, is expected to receive an expanded indication for PsA based upon its strong showing in the AMVISION-1 and -2 trials. Data from those trials, as well as the FUTURE 2 trial for secukinumab and SPIRIT-P1 for ixekizumab, consistently document at least 20% improvement in the ACR criteria for PsA severity – that is, an ACR 20 response – in 50%-60% of patients on one of the three IL-17 inhibitors, as well as ACR 50 response rates of around 30%. Those outcomes are quite consistent with the impact of the anti-TNF biologics on joint disease. But the TNF inhibitors can’t touch the anti–IL-17 biologics when it comes to improvement in Psoriasis Area and Severity Index (PASI) scores: The anti–IL-17 agents have week-52 PASI 75 response rates in the range of 80%, PASI 90 response rates of 70%-75%, and PASI 100 response rates of 40%-55%, with the highest-end results being seen with brodalumab, he continued.

A point worth remembering when prescribing secukinumab is that the approved dose for PsA is 150 mg every 4 weeks, which is just half of the typical dose in psoriasis.

“I spend a lot of time convincing my rheumatology colleagues that if you’re treating both psoriasis and psoriatic arthritis, use the psoriasis dose. There’s some evidence that the higher dose provides some benefit in terms of prevention of permanent joint damage by x-ray,” Dr. Gordon said.

Evidence that TNF inhibitors inhibit permanent joint damage in patients with PsA has been considered a major advantage, establishing this medication class as first-line biologic therapy. But anti–IL-17 therapies appear to have a similar beneficial effect. That was demonstrated in the SPIRIT-P1 trial, where Sharp scores – a radiographic measure of progression of joint damage – were similar at 24 weeks in PsA patients randomized to ixekizumab as compared to adalimumab, with both biologics being superior to placebo. An Assessment of SpondyloArthritis International Society 20% improvement (ASAS 20) response or an ACR 50 response doesn’t capture what’s going on with regard to axial disease. That’s assessed through ASAS 20 and ASAS 40 responses – that is, at least 20% or 40% improvement, compared with baseline, in Assessment in Ankylosing Spondylitis scores. And in the MEASURE 1 and 2 trials, secukinumab achieved robust improvement in axial disease as reflected in favorable ASAS 20 and ASAS 40 responses through 52 weeks in patients with active ankylosing spondylitis.

“The anti–IL-17 agents do actually work in ankylosing spondylitis, which might be a surrogate for the treatment effect in axial psoriatic arthritis,” Dr. Gordon commented.

The phase 3b MAXIMISE trial presented at the 2019 EULAR meeting looked specifically at the impact of secukinumab in patients with psoriatic arthritis with axial involvement. An ASAS 20 response at week 12 was seen in 67% and 65% of patients randomized to secukinumab at 150 or 300 mg, respectively, if they were on concomitant methotrexate, and 64% and 61% if they were not, compared with ASAS 20 rates of 34% and 31% in placebo-treated controls.

“This is the only study of an anti–IL-17 agent that’s been done for axial disease to date in psoriatic arthritis. It’s very, very encouraging,” the dermatologist commented.

 

Durability of response and safety

“In terms of safety, the anti–IL-17s have been a truly remarkable success story. There are very low rates of things to be concerned about,” Dr. Gordon said.

Oral candidiasis occurs in 2%-4% of treated patients, but he noted, “It’s almost always very mild disease” that’s easily treatable with nystatin or, in the worst case, with some fluconazole.

Inflammatory bowel disease (IBD) as a side effect of anti–IL-17 therapy has been a controversial issue. Dr. Gordon’s interpretation of the evidence is that there probably is a very slight increase in the risk of developing ulcerative colitis, but not Crohn’s disease.

“This rate is extraordinarily low, so while it’s something that I consider, and if a patient has a personal history of IBD I will sometimes hesitate to use an anti–IL-17 agent, in patients who don’t have a personal history I’ll go ahead,” he explained.

There is a signal of a slight increase in risk of depression in patients on brodalumab, which isn’t the case for secukinumab or ixekizumab.

Importantly, large long-term extension studies with years of follow-up show that the initially low adverse event rates associated with the IL-17 inhibitors don’t increase over time; rather, they remain steady over years of use.

Long-term maintenance of response with these biologics is impressive. “It’s not perfect, but it’s still a tremendous advantage for patients, especially if you can get them through that initial period,” Dr. Gordon said.

For example, in the long-term extension of the UNCOVER-1 trial, psoriasis patients who had clear or almost clear skin at week 12 on ixekizumab and continued to take the medication open label for 5 years had PASI 75, 90, and 100 response rates of 94%, 82%, and 47%, respectively, at week 264.
 

What about IL-12/23 and IL-23 inhibitors in PsA?

In a separate presentation at the MedscapeLive seminar, Bruce E. Strober, MD, PhD, said that, although ustekinumab (Stelara) is approved for both psoriasis and PsA, the IL-12/-23 inhibitor’s efficacy in PsA is inconsistent and lower than other approved biologics. In contrast, the IL-23 inhibitor guselkumab (Tremfya), which also has the dual indications, is a strong performer in both. In the DISCOVER-2 trial, conducted in treatment-naive patients with PsA, guselkumab at the approved dose of 100 mg every 8 weeks achieved ACR 20, 50, and 70 rates of 64%, 31%, and 19%, respectively. It was also significantly better than placebo for resolution of enthesitis.

An important caveat: While radiographic inhibition of progression of joint disease occurred with guselkumab dosed at 100 mg every 4 weeks in DISCOVER-2, that’s not the approved dose. At 100 mg every 8 weeks – the FDA-approved dosing for both psoriatic arthritis and psoriasis – radiographic inhibition wasn’t better than with placebo, noted Dr. Strober, a dermatologist at Yale University, New Haven, Conn.

Dr. Gordon and Dr. Strober are clinical trialists who reported receiving research support and/or honoraria from more than a dozen pharmaceutical companies, including virtually all of those with biologics for dermatology.

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

bjancin@mdedge.com

LAS VEGAS – Current major guidelines for treatment of psoriatic arthritis (PsA) shortchange the value of the anti–interleukin-17 biologics for this disease, Kenneth B. Gordon, MD, said at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.

The 2018 joint American College of Rheumatology/National Psoriasis Association guidelines recommend the anti–tumor necrosis factor agents as first-line biologic therapy for PsA, with the anti–IL-17 biologics held in reserve as second-tier therapy for when the anti-TNFs don’t work. That’s largely because the guidance was developed before the compelling evidence for the anti–IL-17 agents as the biologics of choice was appreciated, according to Dr. Gordon, professor and chair of the department of dermatology at the Medical College of Wisconsin, Milwaukee.

“Many people go by these guidelines,” the dermatologist noted. “I think it’s really critical to look at the data and not just the guidelines because the guidelines don’t give full credit to the anti–IL-17 agents,” he added.

“Emerging psoriatic arthritis data may likely put this class of medications into the forefront of treatment for patients who have both psoriasis and psoriatic arthritis because you generally get higher responses for the skin disease than with anti-TNF therapy, and with similar responses in psoriatic arthritis.”

Two IL-17 inhibitors are approved for both PsA and psoriasis: secukinumab (Cosentyx) and ixekizumab (Taltz). In addition, brodalumab (Siliq), approved for psoriasis, is expected to receive an expanded indication for PsA based upon its strong showing in the AMVISION-1 and -2 trials. Data from those trials, as well as the FUTURE 2 trial for secukinumab and SPIRIT-P1 for ixekizumab, consistently document at least 20% improvement in the ACR criteria for PsA severity – that is, an ACR 20 response – in 50%-60% of patients on one of the three IL-17 inhibitors, as well as ACR 50 response rates of around 30%. Those outcomes are quite consistent with the impact of the anti-TNF biologics on joint disease. But the TNF inhibitors can’t touch the anti–IL-17 biologics when it comes to improvement in Psoriasis Area and Severity Index (PASI) scores: The anti–IL-17 agents have week-52 PASI 75 response rates in the range of 80%, PASI 90 response rates of 70%-75%, and PASI 100 response rates of 40%-55%, with the highest-end results being seen with brodalumab, he continued.

A point worth remembering when prescribing secukinumab is that the approved dose for PsA is 150 mg every 4 weeks, which is just half of the typical dose in psoriasis.

“I spend a lot of time convincing my rheumatology colleagues that if you’re treating both psoriasis and psoriatic arthritis, use the psoriasis dose. There’s some evidence that the higher dose provides some benefit in terms of prevention of permanent joint damage by x-ray,” Dr. Gordon said.

Evidence that TNF inhibitors inhibit permanent joint damage in patients with PsA has been considered a major advantage, establishing this medication class as first-line biologic therapy. But anti–IL-17 therapies appear to have a similar beneficial effect. That was demonstrated in the SPIRIT-P1 trial, where Sharp scores – a radiographic measure of progression of joint damage – were similar at 24 weeks in PsA patients randomized to ixekizumab as compared to adalimumab, with both biologics being superior to placebo. An Assessment of SpondyloArthritis International Society 20% improvement (ASAS 20) response or an ACR 50 response doesn’t capture what’s going on with regard to axial disease. That’s assessed through ASAS 20 and ASAS 40 responses – that is, at least 20% or 40% improvement, compared with baseline, in Assessment in Ankylosing Spondylitis scores. And in the MEASURE 1 and 2 trials, secukinumab achieved robust improvement in axial disease as reflected in favorable ASAS 20 and ASAS 40 responses through 52 weeks in patients with active ankylosing spondylitis.

“The anti–IL-17 agents do actually work in ankylosing spondylitis, which might be a surrogate for the treatment effect in axial psoriatic arthritis,” Dr. Gordon commented.

The phase 3b MAXIMISE trial presented at the 2019 EULAR meeting looked specifically at the impact of secukinumab in patients with psoriatic arthritis with axial involvement. An ASAS 20 response at week 12 was seen in 67% and 65% of patients randomized to secukinumab at 150 or 300 mg, respectively, if they were on concomitant methotrexate, and 64% and 61% if they were not, compared with ASAS 20 rates of 34% and 31% in placebo-treated controls.

“This is the only study of an anti–IL-17 agent that’s been done for axial disease to date in psoriatic arthritis. It’s very, very encouraging,” the dermatologist commented.

 

Durability of response and safety

“In terms of safety, the anti–IL-17s have been a truly remarkable success story. There are very low rates of things to be concerned about,” Dr. Gordon said.

Oral candidiasis occurs in 2%-4% of treated patients, but he noted, “It’s almost always very mild disease” that’s easily treatable with nystatin or, in the worst case, with some fluconazole.

Inflammatory bowel disease (IBD) as a side effect of anti–IL-17 therapy has been a controversial issue. Dr. Gordon’s interpretation of the evidence is that there probably is a very slight increase in the risk of developing ulcerative colitis, but not Crohn’s disease.

“This rate is extraordinarily low, so while it’s something that I consider, and if a patient has a personal history of IBD I will sometimes hesitate to use an anti–IL-17 agent, in patients who don’t have a personal history I’ll go ahead,” he explained.

There is a signal of a slight increase in risk of depression in patients on brodalumab, which isn’t the case for secukinumab or ixekizumab.

Importantly, large long-term extension studies with years of follow-up show that the initially low adverse event rates associated with the IL-17 inhibitors don’t increase over time; rather, they remain steady over years of use.

Long-term maintenance of response with these biologics is impressive. “It’s not perfect, but it’s still a tremendous advantage for patients, especially if you can get them through that initial period,” Dr. Gordon said.

For example, in the long-term extension of the UNCOVER-1 trial, psoriasis patients who had clear or almost clear skin at week 12 on ixekizumab and continued to take the medication open label for 5 years had PASI 75, 90, and 100 response rates of 94%, 82%, and 47%, respectively, at week 264.
 

What about IL-12/23 and IL-23 inhibitors in PsA?

In a separate presentation at the MedscapeLive seminar, Bruce E. Strober, MD, PhD, said that, although ustekinumab (Stelara) is approved for both psoriasis and PsA, the IL-12/-23 inhibitor’s efficacy in PsA is inconsistent and lower than other approved biologics. In contrast, the IL-23 inhibitor guselkumab (Tremfya), which also has the dual indications, is a strong performer in both. In the DISCOVER-2 trial, conducted in treatment-naive patients with PsA, guselkumab at the approved dose of 100 mg every 8 weeks achieved ACR 20, 50, and 70 rates of 64%, 31%, and 19%, respectively. It was also significantly better than placebo for resolution of enthesitis.

An important caveat: While radiographic inhibition of progression of joint disease occurred with guselkumab dosed at 100 mg every 4 weeks in DISCOVER-2, that’s not the approved dose. At 100 mg every 8 weeks – the FDA-approved dosing for both psoriatic arthritis and psoriasis – radiographic inhibition wasn’t better than with placebo, noted Dr. Strober, a dermatologist at Yale University, New Haven, Conn.

Dr. Gordon and Dr. Strober are clinical trialists who reported receiving research support and/or honoraria from more than a dozen pharmaceutical companies, including virtually all of those with biologics for dermatology.

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

bjancin@mdedge.com

LAS VEGAS – Current major guidelines for treatment of psoriatic arthritis (PsA) shortchange the value of the anti–interleukin-17 biologics for this disease, Kenneth B. Gordon, MD, said at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.

The 2018 joint American College of Rheumatology/National Psoriasis Association guidelines recommend the anti–tumor necrosis factor agents as first-line biologic therapy for PsA, with the anti–IL-17 biologics held in reserve as second-tier therapy for when the anti-TNFs don’t work. That’s largely because the guidance was developed before the compelling evidence for the anti–IL-17 agents as the biologics of choice was appreciated, according to Dr. Gordon, professor and chair of the department of dermatology at the Medical College of Wisconsin, Milwaukee.

“Many people go by these guidelines,” the dermatologist noted. “I think it’s really critical to look at the data and not just the guidelines because the guidelines don’t give full credit to the anti–IL-17 agents,” he added.

“Emerging psoriatic arthritis data may likely put this class of medications into the forefront of treatment for patients who have both psoriasis and psoriatic arthritis because you generally get higher responses for the skin disease than with anti-TNF therapy, and with similar responses in psoriatic arthritis.”

Two IL-17 inhibitors are approved for both PsA and psoriasis: secukinumab (Cosentyx) and ixekizumab (Taltz). In addition, brodalumab (Siliq), approved for psoriasis, is expected to receive an expanded indication for PsA based upon its strong showing in the AMVISION-1 and -2 trials. Data from those trials, as well as the FUTURE 2 trial for secukinumab and SPIRIT-P1 for ixekizumab, consistently document at least 20% improvement in the ACR criteria for PsA severity – that is, an ACR 20 response – in 50%-60% of patients on one of the three IL-17 inhibitors, as well as ACR 50 response rates of around 30%. Those outcomes are quite consistent with the impact of the anti-TNF biologics on joint disease. But the TNF inhibitors can’t touch the anti–IL-17 biologics when it comes to improvement in Psoriasis Area and Severity Index (PASI) scores: The anti–IL-17 agents have week-52 PASI 75 response rates in the range of 80%, PASI 90 response rates of 70%-75%, and PASI 100 response rates of 40%-55%, with the highest-end results being seen with brodalumab, he continued.

A point worth remembering when prescribing secukinumab is that the approved dose for PsA is 150 mg every 4 weeks, which is just half of the typical dose in psoriasis.

“I spend a lot of time convincing my rheumatology colleagues that if you’re treating both psoriasis and psoriatic arthritis, use the psoriasis dose. There’s some evidence that the higher dose provides some benefit in terms of prevention of permanent joint damage by x-ray,” Dr. Gordon said.

Evidence that TNF inhibitors inhibit permanent joint damage in patients with PsA has been considered a major advantage, establishing this medication class as first-line biologic therapy. But anti–IL-17 therapies appear to have a similar beneficial effect. That was demonstrated in the SPIRIT-P1 trial, where Sharp scores – a radiographic measure of progression of joint damage – were similar at 24 weeks in PsA patients randomized to ixekizumab as compared to adalimumab, with both biologics being superior to placebo. An Assessment of SpondyloArthritis International Society 20% improvement (ASAS 20) response or an ACR 50 response doesn’t capture what’s going on with regard to axial disease. That’s assessed through ASAS 20 and ASAS 40 responses – that is, at least 20% or 40% improvement, compared with baseline, in Assessment in Ankylosing Spondylitis scores. And in the MEASURE 1 and 2 trials, secukinumab achieved robust improvement in axial disease as reflected in favorable ASAS 20 and ASAS 40 responses through 52 weeks in patients with active ankylosing spondylitis.

“The anti–IL-17 agents do actually work in ankylosing spondylitis, which might be a surrogate for the treatment effect in axial psoriatic arthritis,” Dr. Gordon commented.

The phase 3b MAXIMISE trial presented at the 2019 EULAR meeting looked specifically at the impact of secukinumab in patients with psoriatic arthritis with axial involvement. An ASAS 20 response at week 12 was seen in 67% and 65% of patients randomized to secukinumab at 150 or 300 mg, respectively, if they were on concomitant methotrexate, and 64% and 61% if they were not, compared with ASAS 20 rates of 34% and 31% in placebo-treated controls.

“This is the only study of an anti–IL-17 agent that’s been done for axial disease to date in psoriatic arthritis. It’s very, very encouraging,” the dermatologist commented.

 

Durability of response and safety

“In terms of safety, the anti–IL-17s have been a truly remarkable success story. There are very low rates of things to be concerned about,” Dr. Gordon said.

Oral candidiasis occurs in 2%-4% of treated patients, but he noted, “It’s almost always very mild disease” that’s easily treatable with nystatin or, in the worst case, with some fluconazole.

Inflammatory bowel disease (IBD) as a side effect of anti–IL-17 therapy has been a controversial issue. Dr. Gordon’s interpretation of the evidence is that there probably is a very slight increase in the risk of developing ulcerative colitis, but not Crohn’s disease.

“This rate is extraordinarily low, so while it’s something that I consider, and if a patient has a personal history of IBD I will sometimes hesitate to use an anti–IL-17 agent, in patients who don’t have a personal history I’ll go ahead,” he explained.

There is a signal of a slight increase in risk of depression in patients on brodalumab, which isn’t the case for secukinumab or ixekizumab.

Importantly, large long-term extension studies with years of follow-up show that the initially low adverse event rates associated with the IL-17 inhibitors don’t increase over time; rather, they remain steady over years of use.

Long-term maintenance of response with these biologics is impressive. “It’s not perfect, but it’s still a tremendous advantage for patients, especially if you can get them through that initial period,” Dr. Gordon said.

For example, in the long-term extension of the UNCOVER-1 trial, psoriasis patients who had clear or almost clear skin at week 12 on ixekizumab and continued to take the medication open label for 5 years had PASI 75, 90, and 100 response rates of 94%, 82%, and 47%, respectively, at week 264.
 

What about IL-12/23 and IL-23 inhibitors in PsA?

In a separate presentation at the MedscapeLive seminar, Bruce E. Strober, MD, PhD, said that, although ustekinumab (Stelara) is approved for both psoriasis and PsA, the IL-12/-23 inhibitor’s efficacy in PsA is inconsistent and lower than other approved biologics. In contrast, the IL-23 inhibitor guselkumab (Tremfya), which also has the dual indications, is a strong performer in both. In the DISCOVER-2 trial, conducted in treatment-naive patients with PsA, guselkumab at the approved dose of 100 mg every 8 weeks achieved ACR 20, 50, and 70 rates of 64%, 31%, and 19%, respectively. It was also significantly better than placebo for resolution of enthesitis.

An important caveat: While radiographic inhibition of progression of joint disease occurred with guselkumab dosed at 100 mg every 4 weeks in DISCOVER-2, that’s not the approved dose. At 100 mg every 8 weeks – the FDA-approved dosing for both psoriatic arthritis and psoriasis – radiographic inhibition wasn’t better than with placebo, noted Dr. Strober, a dermatologist at Yale University, New Haven, Conn.

Dr. Gordon and Dr. Strober are clinical trialists who reported receiving research support and/or honoraria from more than a dozen pharmaceutical companies, including virtually all of those with biologics for dermatology.

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

bjancin@mdedge.com

Big changes are coming in the use of oral apremilast, currently approved for moderate to severe psoriasis and plaque psoriasis in adults, Bruce E. Strober, MD, PhD, predicted at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.

“We’ll have a pediatric indication for apremilast in psoriasis down the line, and probably a mild to moderate indication for psoriasis, meaning we can use this drug in patients in whom we typically think about using only topical therapies. Keep on the lookout: I think the mild to moderate indication may be coming next year, and that’s going to really shake up the whole landscape of psoriasis therapy,” said Dr. Strober, a dermatologist at Yale University in New Haven, Conn., and Central Connecticut Dermatology in Cromwell, Conn.
 

Mild or moderate psoriasis

Apremilast manufacturer Amgen has announced positive topline results from the phase 3 ADVANCE trial, a multicenter, placebo-controlled, double-blind, study of 595 patients with mild or moderate psoriasis as defined by an involved body surface area of 2%-15% and a Psoriasis Area and Severity Index score of 2-15. Participants were randomized to the approved dose of apremilast (Otezla) – 30 mg twice daily – or placebo for 16 weeks, followed by 16 weeks of open-label apremilast for all. The full study findings haven’t yet been published or presented at a medical conference, but Amgen announced that the results were positive for all primary and secondary endpoints, and the company plans to file a request with the Food and Drug Administration for an expanded indication for the oral agent.

Pediatric studies

A recently published phase 2, open-label, 1-year study of apremilast in 42 children and adolescents with moderate to severe plaque psoriasis demonstrated that weight-based dosing is the best approach in the pediatric population. The study, which serves as the template for coming phase 3 trials, showed that dosing apremilast at 20 mg twice daily in youths weighing not more than 35 kg and 30 mg twice daily in those who weighed more provided pharmacokinetic exposure similar to that achieved with apremilast at the standard adult dose of 30 mg twice daily. Most participants liked the taste of the tablet.

“My prediction is apremilast will have efficacy in children and teenagers comparable to what it has in adults, with a similar safety and adverse event profile,” Dr. Strober said.

Apremilast works by blocking phosphodiesterase type 4, thereby reducing cyclic AMP metabolism, with a resultant increase in cyclic AMP levels. Cyclic AMP is a regulator of inflammation. Boosting its level has the effect of decreasing tumor necrosis factor and other proinflammatory cytokines while increasing anti-inflammatory mediators, such as interleukin-10.

Dr. Strober characterized apremilast’s efficacy as “modest” by contemporary standards in adults with moderate to severe psoriasis, with week 16 PASI 75 rates of about 30% in randomized trials, compared with 5% in placebo-treated controls. He considers it a good option in patients with moderate disease who are needle phobic and in those averse to the inconvenience of laboratory monitoring. The drug is useful in treating psoriasis in especially challenging locations. Apremilast is specifically approved for scalp psoriasis, and Dr. Strober has anecdotally found it helpful in patients with palmoplantar psoriasis or genital psoriasis.

“Apremilast has tolerability issues: first and foremost diarrhea, nausea, and headache. Probably 15%-20% of patients have nausea or diarrhea ranging from mild to severe, and 1 in 20 have headache. You have to warn patients,” he said.

Roughly 1% of patients experience depressed mood. “I’ve seen it in a few patients. I definitely believe it’s real, so query patients about mood changes while taking apremilast,” the dermatologist advised.

One in 5 patients loses 5% of body weight during the first 6 months on apremilast, but there’s no additional weight loss thereafter. It’s wrong to characterize the oral agent as a weight-loss drug, though, since 80% of patients don’t lose weight, Dr. Strober noted.
 

Topical PDE-4 inhibitor shows promise

Separately at the Las Vegas meeting, Linda Stein Gold, MD, provided highlights of a phase 2b randomized trial of a topical cream formulation of an extremely potent PDE-4 inhibitor, roflumilast, in patients with chronic plaque psoriasis. This molecule is a couple hundred times more effective at inhibiting the PDE-4 receptor than either oral apremilast or topical crisaborole (Eucrisa). And as a once-daily topical agent with very little systemic absorption, roflumilast cream sidesteps the tolerability issues that accompany apremilast.

“Roflumilast is currently available as an oral formulation for treatment of [chronic obstructive pulmonary disease], so it has a fairly well-established safety profile,” noted Dr. Stein Gold, director of dermatology clinical research at the Henry Ford Health System in Detroit.

The 12-week, multicenter, phase 2b study sponsored by Arcutis Biotherapeutics included 331 patients with chronic plaque psoriasis who were randomized to once-daily 0.3% roflumilast cream, 0.15% roflumilast cream, or vehicle. Three-quarters of participants had baseline moderate disease.

A week-8 Investigator’s Global Assessment (IGA) score of 0 or 1, meaning clear skin or almost clear, plus at least a 2-grade improvement from baseline occurred in 32% of the high-dose roflumilast group, 25% of those on the 0.15% formulation, and 10% of controls. On the secondary endpoint of improvement in tough-to-treat intertriginous psoriasis, at week 12 an intertriginous IGA score of 0 or 1 plus at least a 2-point improvement from baseline was seen in 86% of the 0.3% roflumilast cream group, 50% on low-dose therapy, and 29% of controls. Moreover, the clinical improvements in IGA and itch kicked in quickly, with significant separation from placebo by week 2, Dr. Stein Gold noted.

The phase 3 program is now recruiting participants.

Dr. Strober and Dr. Stein Gold reported receiving research funding from and serving as consultants to Amgen and numerous other pharmaceutical companies.

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

bjancin@mdedge.com

Big changes are coming in the use of oral apremilast, currently approved for moderate to severe psoriasis and plaque psoriasis in adults, Bruce E. Strober, MD, PhD, predicted at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.

“We’ll have a pediatric indication for apremilast in psoriasis down the line, and probably a mild to moderate indication for psoriasis, meaning we can use this drug in patients in whom we typically think about using only topical therapies. Keep on the lookout: I think the mild to moderate indication may be coming next year, and that’s going to really shake up the whole landscape of psoriasis therapy,” said Dr. Strober, a dermatologist at Yale University in New Haven, Conn., and Central Connecticut Dermatology in Cromwell, Conn.
 

Mild or moderate psoriasis

Apremilast manufacturer Amgen has announced positive topline results from the phase 3 ADVANCE trial, a multicenter, placebo-controlled, double-blind, study of 595 patients with mild or moderate psoriasis as defined by an involved body surface area of 2%-15% and a Psoriasis Area and Severity Index score of 2-15. Participants were randomized to the approved dose of apremilast (Otezla) – 30 mg twice daily – or placebo for 16 weeks, followed by 16 weeks of open-label apremilast for all. The full study findings haven’t yet been published or presented at a medical conference, but Amgen announced that the results were positive for all primary and secondary endpoints, and the company plans to file a request with the Food and Drug Administration for an expanded indication for the oral agent.

Pediatric studies

A recently published phase 2, open-label, 1-year study of apremilast in 42 children and adolescents with moderate to severe plaque psoriasis demonstrated that weight-based dosing is the best approach in the pediatric population. The study, which serves as the template for coming phase 3 trials, showed that dosing apremilast at 20 mg twice daily in youths weighing not more than 35 kg and 30 mg twice daily in those who weighed more provided pharmacokinetic exposure similar to that achieved with apremilast at the standard adult dose of 30 mg twice daily. Most participants liked the taste of the tablet.

“My prediction is apremilast will have efficacy in children and teenagers comparable to what it has in adults, with a similar safety and adverse event profile,” Dr. Strober said.

Apremilast works by blocking phosphodiesterase type 4, thereby reducing cyclic AMP metabolism, with a resultant increase in cyclic AMP levels. Cyclic AMP is a regulator of inflammation. Boosting its level has the effect of decreasing tumor necrosis factor and other proinflammatory cytokines while increasing anti-inflammatory mediators, such as interleukin-10.

Dr. Strober characterized apremilast’s efficacy as “modest” by contemporary standards in adults with moderate to severe psoriasis, with week 16 PASI 75 rates of about 30% in randomized trials, compared with 5% in placebo-treated controls. He considers it a good option in patients with moderate disease who are needle phobic and in those averse to the inconvenience of laboratory monitoring. The drug is useful in treating psoriasis in especially challenging locations. Apremilast is specifically approved for scalp psoriasis, and Dr. Strober has anecdotally found it helpful in patients with palmoplantar psoriasis or genital psoriasis.

“Apremilast has tolerability issues: first and foremost diarrhea, nausea, and headache. Probably 15%-20% of patients have nausea or diarrhea ranging from mild to severe, and 1 in 20 have headache. You have to warn patients,” he said.

Roughly 1% of patients experience depressed mood. “I’ve seen it in a few patients. I definitely believe it’s real, so query patients about mood changes while taking apremilast,” the dermatologist advised.

One in 5 patients loses 5% of body weight during the first 6 months on apremilast, but there’s no additional weight loss thereafter. It’s wrong to characterize the oral agent as a weight-loss drug, though, since 80% of patients don’t lose weight, Dr. Strober noted.
 

Topical PDE-4 inhibitor shows promise

Separately at the Las Vegas meeting, Linda Stein Gold, MD, provided highlights of a phase 2b randomized trial of a topical cream formulation of an extremely potent PDE-4 inhibitor, roflumilast, in patients with chronic plaque psoriasis. This molecule is a couple hundred times more effective at inhibiting the PDE-4 receptor than either oral apremilast or topical crisaborole (Eucrisa). And as a once-daily topical agent with very little systemic absorption, roflumilast cream sidesteps the tolerability issues that accompany apremilast.

“Roflumilast is currently available as an oral formulation for treatment of [chronic obstructive pulmonary disease], so it has a fairly well-established safety profile,” noted Dr. Stein Gold, director of dermatology clinical research at the Henry Ford Health System in Detroit.

The 12-week, multicenter, phase 2b study sponsored by Arcutis Biotherapeutics included 331 patients with chronic plaque psoriasis who were randomized to once-daily 0.3% roflumilast cream, 0.15% roflumilast cream, or vehicle. Three-quarters of participants had baseline moderate disease.

A week-8 Investigator’s Global Assessment (IGA) score of 0 or 1, meaning clear skin or almost clear, plus at least a 2-grade improvement from baseline occurred in 32% of the high-dose roflumilast group, 25% of those on the 0.15% formulation, and 10% of controls. On the secondary endpoint of improvement in tough-to-treat intertriginous psoriasis, at week 12 an intertriginous IGA score of 0 or 1 plus at least a 2-point improvement from baseline was seen in 86% of the 0.3% roflumilast cream group, 50% on low-dose therapy, and 29% of controls. Moreover, the clinical improvements in IGA and itch kicked in quickly, with significant separation from placebo by week 2, Dr. Stein Gold noted.

The phase 3 program is now recruiting participants.

Dr. Strober and Dr. Stein Gold reported receiving research funding from and serving as consultants to Amgen and numerous other pharmaceutical companies.

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

bjancin@mdedge.com

Big changes are coming in the use of oral apremilast, currently approved for moderate to severe psoriasis and plaque psoriasis in adults, Bruce E. Strober, MD, PhD, predicted at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.

“We’ll have a pediatric indication for apremilast in psoriasis down the line, and probably a mild to moderate indication for psoriasis, meaning we can use this drug in patients in whom we typically think about using only topical therapies. Keep on the lookout: I think the mild to moderate indication may be coming next year, and that’s going to really shake up the whole landscape of psoriasis therapy,” said Dr. Strober, a dermatologist at Yale University in New Haven, Conn., and Central Connecticut Dermatology in Cromwell, Conn.
 

Mild or moderate psoriasis

Apremilast manufacturer Amgen has announced positive topline results from the phase 3 ADVANCE trial, a multicenter, placebo-controlled, double-blind, study of 595 patients with mild or moderate psoriasis as defined by an involved body surface area of 2%-15% and a Psoriasis Area and Severity Index score of 2-15. Participants were randomized to the approved dose of apremilast (Otezla) – 30 mg twice daily – or placebo for 16 weeks, followed by 16 weeks of open-label apremilast for all. The full study findings haven’t yet been published or presented at a medical conference, but Amgen announced that the results were positive for all primary and secondary endpoints, and the company plans to file a request with the Food and Drug Administration for an expanded indication for the oral agent.

Pediatric studies

A recently published phase 2, open-label, 1-year study of apremilast in 42 children and adolescents with moderate to severe plaque psoriasis demonstrated that weight-based dosing is the best approach in the pediatric population. The study, which serves as the template for coming phase 3 trials, showed that dosing apremilast at 20 mg twice daily in youths weighing not more than 35 kg and 30 mg twice daily in those who weighed more provided pharmacokinetic exposure similar to that achieved with apremilast at the standard adult dose of 30 mg twice daily. Most participants liked the taste of the tablet.

“My prediction is apremilast will have efficacy in children and teenagers comparable to what it has in adults, with a similar safety and adverse event profile,” Dr. Strober said.

Apremilast works by blocking phosphodiesterase type 4, thereby reducing cyclic AMP metabolism, with a resultant increase in cyclic AMP levels. Cyclic AMP is a regulator of inflammation. Boosting its level has the effect of decreasing tumor necrosis factor and other proinflammatory cytokines while increasing anti-inflammatory mediators, such as interleukin-10.

Dr. Strober characterized apremilast’s efficacy as “modest” by contemporary standards in adults with moderate to severe psoriasis, with week 16 PASI 75 rates of about 30% in randomized trials, compared with 5% in placebo-treated controls. He considers it a good option in patients with moderate disease who are needle phobic and in those averse to the inconvenience of laboratory monitoring. The drug is useful in treating psoriasis in especially challenging locations. Apremilast is specifically approved for scalp psoriasis, and Dr. Strober has anecdotally found it helpful in patients with palmoplantar psoriasis or genital psoriasis.

“Apremilast has tolerability issues: first and foremost diarrhea, nausea, and headache. Probably 15%-20% of patients have nausea or diarrhea ranging from mild to severe, and 1 in 20 have headache. You have to warn patients,” he said.

Roughly 1% of patients experience depressed mood. “I’ve seen it in a few patients. I definitely believe it’s real, so query patients about mood changes while taking apremilast,” the dermatologist advised.

One in 5 patients loses 5% of body weight during the first 6 months on apremilast, but there’s no additional weight loss thereafter. It’s wrong to characterize the oral agent as a weight-loss drug, though, since 80% of patients don’t lose weight, Dr. Strober noted.
 

Topical PDE-4 inhibitor shows promise

Separately at the Las Vegas meeting, Linda Stein Gold, MD, provided highlights of a phase 2b randomized trial of a topical cream formulation of an extremely potent PDE-4 inhibitor, roflumilast, in patients with chronic plaque psoriasis. This molecule is a couple hundred times more effective at inhibiting the PDE-4 receptor than either oral apremilast or topical crisaborole (Eucrisa). And as a once-daily topical agent with very little systemic absorption, roflumilast cream sidesteps the tolerability issues that accompany apremilast.

“Roflumilast is currently available as an oral formulation for treatment of [chronic obstructive pulmonary disease], so it has a fairly well-established safety profile,” noted Dr. Stein Gold, director of dermatology clinical research at the Henry Ford Health System in Detroit.

The 12-week, multicenter, phase 2b study sponsored by Arcutis Biotherapeutics included 331 patients with chronic plaque psoriasis who were randomized to once-daily 0.3% roflumilast cream, 0.15% roflumilast cream, or vehicle. Three-quarters of participants had baseline moderate disease.

A week-8 Investigator’s Global Assessment (IGA) score of 0 or 1, meaning clear skin or almost clear, plus at least a 2-grade improvement from baseline occurred in 32% of the high-dose roflumilast group, 25% of those on the 0.15% formulation, and 10% of controls. On the secondary endpoint of improvement in tough-to-treat intertriginous psoriasis, at week 12 an intertriginous IGA score of 0 or 1 plus at least a 2-point improvement from baseline was seen in 86% of the 0.3% roflumilast cream group, 50% on low-dose therapy, and 29% of controls. Moreover, the clinical improvements in IGA and itch kicked in quickly, with significant separation from placebo by week 2, Dr. Stein Gold noted.

The phase 3 program is now recruiting participants.

Dr. Strober and Dr. Stein Gold reported receiving research funding from and serving as consultants to Amgen and numerous other pharmaceutical companies.

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

bjancin@mdedge.com

In a single-center retrospective analysis of 102 patients with psoriasis induced by tumor necrosis factor (TNF) inhibitors, most cases improved or resolved with use of topical medications or with discontinuation of the inciting TNF inhibitor, with or without other interventions. All patients were treated and diagnosed by dermatologists.

While TNF inhibitors have revolutionized management of numerous debilitating chronic inflammatory diseases, they are associated with mild and potentially serious adverse reactions, including de novo psoriasiform eruptions, noted Sean E. Mazloom, MD, and colleagues, at the Cleveland Clinic, Cleveland, Ohio, in the Journal of the American Academy of Dermatology. Despite the fact that it has been more than 15 years since the first reports of TNF inhibitor-induced psoriasis, optimal treatment strategies still remain poorly understood.
 

IBD and RA most common

Dr. Mazloom and colleagues identified 102 patients (median onset, 41 years; 72.5% female) with TNF inhibitor-induced psoriasis seen at a single tertiary care institution (the Cleveland Clinic) over a 10-year period. The authors proposed a treatment algorithm based on their findings.

Inciting TNF inhibitors were prescribed most commonly for inflammatory bowel disease (IBD) (52%) and rheumatoid arthritis (RA) (24.5%). The most common inciting TNF inhibitor was infliximab (52%). TNF inhibitor-induced psoriasis improved or resolved with topical medications alone in 63.5% of patients, and cyclosporine and methotrexate (10 mg weekly) were often effective (cyclosporine in five of five patients; methotrexate in 7 of 13) if topicals failed.

Noting that the success with topicals in this cohort exceeded that of earlier reports, the authors suggested that more accurate diagnoses and optimal strategies attributable to the involvement of dermatologists may be explanatory.

In 67% of refractory cases, discontinuation of the inciting TNF inhibitor with or without other interventions improved or resolved TNF inhibitor-induced psoriasis. With switching of TNF inhibitors, persistence or worsening of TNF inhibitor-induced psoriasis was reported in 16 of 25 patients (64%).

Algorithm aims at balancing control

The treatment algorithm proposed by Dr. Mazloom and colleagues aims at balancing control of the primary disease with minimization of skin symptom discomfort and continuation of the inciting TNF inhibitor if possible. Only with cyclosporine or methotrexate failure amid severe symptoms and less-than-optimal primary disease control should TNF inhibitors be discontinued and biologics and/or small-molecule inhibitors with alternative mechanisms of action be introduced. Transitioning to other TNF inhibitors may be tried before alternative strategies when the underlying disease is well-controlled but TNF inhibitor-induced psoriasis remains severe.

“Most dermatologists who see TNF-induced psoriasis often are likely already using strategies like the one proposed in the algorithm,” commented senior author Anthony Fernandez, MD, PhD, of the Cleveland (Ohio) Clinic, in an interview. “The concern is over those who may not see TNF inhibitor-induced psoriasis very often, and who may, as a knee-jerk response to TNF-induced psoriasis, stop the inciting medication. When strong side effects occur in IBD and RA, it’s critical to know how well the TNF inhibitor is controlling the underlying disease because lack of control can lead to permanent damage.”

Risk to benefit ratio favors retaining TNF inhibitors

The dermatologist’s goal, if the TNF inhibitor is working well, should be to exhaust all reasonable options to control the psoriasiform eruption and keep the patient on the TNF inhibitor rather than turn to potentially less effective alternatives, Dr. Fernandez added. “The risk:benefit ratio still usually favors adding more immune therapies to treat these reactions in order to enable patients to stay” on their TNF inhibitors.

Study authors disclosed no direct funding for the study. Dr Fernandez, the senior author, receives research funding from Pfizer, Mallinckrodt, and Novartis, consults for AbbVie and Celgene, and is a speaker for AbbVie and Mallinckrodt.

SOURCE: Mazloom SE et al. J Am Acad Dermatol. 2020 Dec;83(6):1590-8.

In a single-center retrospective analysis of 102 patients with psoriasis induced by tumor necrosis factor (TNF) inhibitors, most cases improved or resolved with use of topical medications or with discontinuation of the inciting TNF inhibitor, with or without other interventions. All patients were treated and diagnosed by dermatologists.

While TNF inhibitors have revolutionized management of numerous debilitating chronic inflammatory diseases, they are associated with mild and potentially serious adverse reactions, including de novo psoriasiform eruptions, noted Sean E. Mazloom, MD, and colleagues, at the Cleveland Clinic, Cleveland, Ohio, in the Journal of the American Academy of Dermatology. Despite the fact that it has been more than 15 years since the first reports of TNF inhibitor-induced psoriasis, optimal treatment strategies still remain poorly understood.
 

IBD and RA most common

Dr. Mazloom and colleagues identified 102 patients (median onset, 41 years; 72.5% female) with TNF inhibitor-induced psoriasis seen at a single tertiary care institution (the Cleveland Clinic) over a 10-year period. The authors proposed a treatment algorithm based on their findings.

Inciting TNF inhibitors were prescribed most commonly for inflammatory bowel disease (IBD) (52%) and rheumatoid arthritis (RA) (24.5%). The most common inciting TNF inhibitor was infliximab (52%). TNF inhibitor-induced psoriasis improved or resolved with topical medications alone in 63.5% of patients, and cyclosporine and methotrexate (10 mg weekly) were often effective (cyclosporine in five of five patients; methotrexate in 7 of 13) if topicals failed.

Noting that the success with topicals in this cohort exceeded that of earlier reports, the authors suggested that more accurate diagnoses and optimal strategies attributable to the involvement of dermatologists may be explanatory.

In 67% of refractory cases, discontinuation of the inciting TNF inhibitor with or without other interventions improved or resolved TNF inhibitor-induced psoriasis. With switching of TNF inhibitors, persistence or worsening of TNF inhibitor-induced psoriasis was reported in 16 of 25 patients (64%).

Algorithm aims at balancing control

The treatment algorithm proposed by Dr. Mazloom and colleagues aims at balancing control of the primary disease with minimization of skin symptom discomfort and continuation of the inciting TNF inhibitor if possible. Only with cyclosporine or methotrexate failure amid severe symptoms and less-than-optimal primary disease control should TNF inhibitors be discontinued and biologics and/or small-molecule inhibitors with alternative mechanisms of action be introduced. Transitioning to other TNF inhibitors may be tried before alternative strategies when the underlying disease is well-controlled but TNF inhibitor-induced psoriasis remains severe.

“Most dermatologists who see TNF-induced psoriasis often are likely already using strategies like the one proposed in the algorithm,” commented senior author Anthony Fernandez, MD, PhD, of the Cleveland (Ohio) Clinic, in an interview. “The concern is over those who may not see TNF inhibitor-induced psoriasis very often, and who may, as a knee-jerk response to TNF-induced psoriasis, stop the inciting medication. When strong side effects occur in IBD and RA, it’s critical to know how well the TNF inhibitor is controlling the underlying disease because lack of control can lead to permanent damage.”

Risk to benefit ratio favors retaining TNF inhibitors

The dermatologist’s goal, if the TNF inhibitor is working well, should be to exhaust all reasonable options to control the psoriasiform eruption and keep the patient on the TNF inhibitor rather than turn to potentially less effective alternatives, Dr. Fernandez added. “The risk:benefit ratio still usually favors adding more immune therapies to treat these reactions in order to enable patients to stay” on their TNF inhibitors.

Study authors disclosed no direct funding for the study. Dr Fernandez, the senior author, receives research funding from Pfizer, Mallinckrodt, and Novartis, consults for AbbVie and Celgene, and is a speaker for AbbVie and Mallinckrodt.

SOURCE: Mazloom SE et al. J Am Acad Dermatol. 2020 Dec;83(6):1590-8.

In a single-center retrospective analysis of 102 patients with psoriasis induced by tumor necrosis factor (TNF) inhibitors, most cases improved or resolved with use of topical medications or with discontinuation of the inciting TNF inhibitor, with or without other interventions. All patients were treated and diagnosed by dermatologists.

While TNF inhibitors have revolutionized management of numerous debilitating chronic inflammatory diseases, they are associated with mild and potentially serious adverse reactions, including de novo psoriasiform eruptions, noted Sean E. Mazloom, MD, and colleagues, at the Cleveland Clinic, Cleveland, Ohio, in the Journal of the American Academy of Dermatology. Despite the fact that it has been more than 15 years since the first reports of TNF inhibitor-induced psoriasis, optimal treatment strategies still remain poorly understood.
 

IBD and RA most common

Dr. Mazloom and colleagues identified 102 patients (median onset, 41 years; 72.5% female) with TNF inhibitor-induced psoriasis seen at a single tertiary care institution (the Cleveland Clinic) over a 10-year period. The authors proposed a treatment algorithm based on their findings.

Inciting TNF inhibitors were prescribed most commonly for inflammatory bowel disease (IBD) (52%) and rheumatoid arthritis (RA) (24.5%). The most common inciting TNF inhibitor was infliximab (52%). TNF inhibitor-induced psoriasis improved or resolved with topical medications alone in 63.5% of patients, and cyclosporine and methotrexate (10 mg weekly) were often effective (cyclosporine in five of five patients; methotrexate in 7 of 13) if topicals failed.

Noting that the success with topicals in this cohort exceeded that of earlier reports, the authors suggested that more accurate diagnoses and optimal strategies attributable to the involvement of dermatologists may be explanatory.

In 67% of refractory cases, discontinuation of the inciting TNF inhibitor with or without other interventions improved or resolved TNF inhibitor-induced psoriasis. With switching of TNF inhibitors, persistence or worsening of TNF inhibitor-induced psoriasis was reported in 16 of 25 patients (64%).

Algorithm aims at balancing control

The treatment algorithm proposed by Dr. Mazloom and colleagues aims at balancing control of the primary disease with minimization of skin symptom discomfort and continuation of the inciting TNF inhibitor if possible. Only with cyclosporine or methotrexate failure amid severe symptoms and less-than-optimal primary disease control should TNF inhibitors be discontinued and biologics and/or small-molecule inhibitors with alternative mechanisms of action be introduced. Transitioning to other TNF inhibitors may be tried before alternative strategies when the underlying disease is well-controlled but TNF inhibitor-induced psoriasis remains severe.

“Most dermatologists who see TNF-induced psoriasis often are likely already using strategies like the one proposed in the algorithm,” commented senior author Anthony Fernandez, MD, PhD, of the Cleveland (Ohio) Clinic, in an interview. “The concern is over those who may not see TNF inhibitor-induced psoriasis very often, and who may, as a knee-jerk response to TNF-induced psoriasis, stop the inciting medication. When strong side effects occur in IBD and RA, it’s critical to know how well the TNF inhibitor is controlling the underlying disease because lack of control can lead to permanent damage.”

Risk to benefit ratio favors retaining TNF inhibitors

The dermatologist’s goal, if the TNF inhibitor is working well, should be to exhaust all reasonable options to control the psoriasiform eruption and keep the patient on the TNF inhibitor rather than turn to potentially less effective alternatives, Dr. Fernandez added. “The risk:benefit ratio still usually favors adding more immune therapies to treat these reactions in order to enable patients to stay” on their TNF inhibitors.

Study authors disclosed no direct funding for the study. Dr Fernandez, the senior author, receives research funding from Pfizer, Mallinckrodt, and Novartis, consults for AbbVie and Celgene, and is a speaker for AbbVie and Mallinckrodt.

SOURCE: Mazloom SE et al. J Am Acad Dermatol. 2020 Dec;83(6):1590-8.

The full 5-year results of a long-term extension study of tildrakizumab for psoriasis show a high rate of sustained disease control coupled with a favorable safety profile during more than 5,400 patient-years of prospective follow-up, Diamont Thaçi, MD, PhD, reported at the virtual annual congress of the European Academy of Dermatology and Venereology.

For example, 89% of patients who had a PASI-75 response on the 100-mg dose of tildrakizumab (Ilumya) – the dose approved in the United States – at week 28 in the parent reSURFACE 1 and reSURFACE 2 trials maintained their PASI-75 response throughout the next 4½ years in the long-term extension study, as did 93% of those with a week 28 PASI-75 response on 200 mg, a dose approved elsewhere, said Dr. Thaçi, professor of dermatology and director of the Comprehensive Center for Inflammation Medicine at Lübeck (Germany) University.

The same held true for PASI-90, a response achieved by 71% of participants on 100 mg of tildrakizumab at week 28 and 66% at week 244, and by 73% of those on the 200-mg dose at week 28 and 70% at 5 years. A PASI-100 response was documented at week 28 in 29% of patients on the lower dose and 37% of those on 200 mg, with week 244 PASI-100 rates of 33% and 41%, respectively.

The long-term extension study enrolled 622 patients with moderate to severe chronic plaque psoriasis with at least a PASI-75 response to 100 mg or 200 mg of the humanized monoclonal antibody interleukin-23p19 inhibitor at week 28 in reSURFACE 1 or 2, or who were partial or nonresponders to etanercept in reSURFACE 2 and were then switched to tildrakizumab at 200 mg. Five hundred and forty-five of the 622 patients (88%) completed the full 5 years of the extension study.

Very few patients left the study because of loss of efficacy or adverse events. Indeed, the exposure-adjusted rate of drug-related serious adverse events was 0.8 cases per 100 patient-years at tildrakizumab 100 mg and 0.5 per 100 patient-years at 200 mg. Moreover, the rates of drug-related serious adverse events leading to treatment continuation were 0.3 and 0.2 per 100 patient-years at the 100-mg and 200-mg doses. Rates of treatment-emergent severe infection were 1.2 and 1.3 per 100 patient-years on the lower and higher doses. Major adverse cardiovascular events occurred at rates of 0.5 and 0.7 cases per 100 patient-years.

“I think the adverse events are generally similar to what has been seen with other biologics, but slightly less with tildrakizumab. Registries will provide a clearer picture. What’s interesting is that even if you double the dosage you don’t see an increase in side effects,” Dr. Thaçi said.

Asked what happens when a tildrakizumab responder stops taking the monoclonal antibody, he replied, “This is something very interesting we see with the IL-23 inhibitors: The disease comes back very slowly. It takes months, and sometimes years, for the patient to lose the PASI-75 or even the PASI-90 response. But we still consider that continuous treatment is probably the better way to go because we cannot be sure who will lose or regain response. At the moment we don’t have a biomarker to tell us what we should do in our daily practice.”

Dr. Thaçi reported serving as an adviser to and paid investigator for Almirall, the study sponsor, and approximately 20 other pharmaceutical companies.

bjancin@mdedge.com

The full 5-year results of a long-term extension study of tildrakizumab for psoriasis show a high rate of sustained disease control coupled with a favorable safety profile during more than 5,400 patient-years of prospective follow-up, Diamont Thaçi, MD, PhD, reported at the virtual annual congress of the European Academy of Dermatology and Venereology.

For example, 89% of patients who had a PASI-75 response on the 100-mg dose of tildrakizumab (Ilumya) – the dose approved in the United States – at week 28 in the parent reSURFACE 1 and reSURFACE 2 trials maintained their PASI-75 response throughout the next 4½ years in the long-term extension study, as did 93% of those with a week 28 PASI-75 response on 200 mg, a dose approved elsewhere, said Dr. Thaçi, professor of dermatology and director of the Comprehensive Center for Inflammation Medicine at Lübeck (Germany) University.

The same held true for PASI-90, a response achieved by 71% of participants on 100 mg of tildrakizumab at week 28 and 66% at week 244, and by 73% of those on the 200-mg dose at week 28 and 70% at 5 years. A PASI-100 response was documented at week 28 in 29% of patients on the lower dose and 37% of those on 200 mg, with week 244 PASI-100 rates of 33% and 41%, respectively.

The long-term extension study enrolled 622 patients with moderate to severe chronic plaque psoriasis with at least a PASI-75 response to 100 mg or 200 mg of the humanized monoclonal antibody interleukin-23p19 inhibitor at week 28 in reSURFACE 1 or 2, or who were partial or nonresponders to etanercept in reSURFACE 2 and were then switched to tildrakizumab at 200 mg. Five hundred and forty-five of the 622 patients (88%) completed the full 5 years of the extension study.

Very few patients left the study because of loss of efficacy or adverse events. Indeed, the exposure-adjusted rate of drug-related serious adverse events was 0.8 cases per 100 patient-years at tildrakizumab 100 mg and 0.5 per 100 patient-years at 200 mg. Moreover, the rates of drug-related serious adverse events leading to treatment continuation were 0.3 and 0.2 per 100 patient-years at the 100-mg and 200-mg doses. Rates of treatment-emergent severe infection were 1.2 and 1.3 per 100 patient-years on the lower and higher doses. Major adverse cardiovascular events occurred at rates of 0.5 and 0.7 cases per 100 patient-years.

“I think the adverse events are generally similar to what has been seen with other biologics, but slightly less with tildrakizumab. Registries will provide a clearer picture. What’s interesting is that even if you double the dosage you don’t see an increase in side effects,” Dr. Thaçi said.

Asked what happens when a tildrakizumab responder stops taking the monoclonal antibody, he replied, “This is something very interesting we see with the IL-23 inhibitors: The disease comes back very slowly. It takes months, and sometimes years, for the patient to lose the PASI-75 or even the PASI-90 response. But we still consider that continuous treatment is probably the better way to go because we cannot be sure who will lose or regain response. At the moment we don’t have a biomarker to tell us what we should do in our daily practice.”

Dr. Thaçi reported serving as an adviser to and paid investigator for Almirall, the study sponsor, and approximately 20 other pharmaceutical companies.

bjancin@mdedge.com

The full 5-year results of a long-term extension study of tildrakizumab for psoriasis show a high rate of sustained disease control coupled with a favorable safety profile during more than 5,400 patient-years of prospective follow-up, Diamont Thaçi, MD, PhD, reported at the virtual annual congress of the European Academy of Dermatology and Venereology.

For example, 89% of patients who had a PASI-75 response on the 100-mg dose of tildrakizumab (Ilumya) – the dose approved in the United States – at week 28 in the parent reSURFACE 1 and reSURFACE 2 trials maintained their PASI-75 response throughout the next 4½ years in the long-term extension study, as did 93% of those with a week 28 PASI-75 response on 200 mg, a dose approved elsewhere, said Dr. Thaçi, professor of dermatology and director of the Comprehensive Center for Inflammation Medicine at Lübeck (Germany) University.

The same held true for PASI-90, a response achieved by 71% of participants on 100 mg of tildrakizumab at week 28 and 66% at week 244, and by 73% of those on the 200-mg dose at week 28 and 70% at 5 years. A PASI-100 response was documented at week 28 in 29% of patients on the lower dose and 37% of those on 200 mg, with week 244 PASI-100 rates of 33% and 41%, respectively.

The long-term extension study enrolled 622 patients with moderate to severe chronic plaque psoriasis with at least a PASI-75 response to 100 mg or 200 mg of the humanized monoclonal antibody interleukin-23p19 inhibitor at week 28 in reSURFACE 1 or 2, or who were partial or nonresponders to etanercept in reSURFACE 2 and were then switched to tildrakizumab at 200 mg. Five hundred and forty-five of the 622 patients (88%) completed the full 5 years of the extension study.

Very few patients left the study because of loss of efficacy or adverse events. Indeed, the exposure-adjusted rate of drug-related serious adverse events was 0.8 cases per 100 patient-years at tildrakizumab 100 mg and 0.5 per 100 patient-years at 200 mg. Moreover, the rates of drug-related serious adverse events leading to treatment continuation were 0.3 and 0.2 per 100 patient-years at the 100-mg and 200-mg doses. Rates of treatment-emergent severe infection were 1.2 and 1.3 per 100 patient-years on the lower and higher doses. Major adverse cardiovascular events occurred at rates of 0.5 and 0.7 cases per 100 patient-years.

“I think the adverse events are generally similar to what has been seen with other biologics, but slightly less with tildrakizumab. Registries will provide a clearer picture. What’s interesting is that even if you double the dosage you don’t see an increase in side effects,” Dr. Thaçi said.

Asked what happens when a tildrakizumab responder stops taking the monoclonal antibody, he replied, “This is something very interesting we see with the IL-23 inhibitors: The disease comes back very slowly. It takes months, and sometimes years, for the patient to lose the PASI-75 or even the PASI-90 response. But we still consider that continuous treatment is probably the better way to go because we cannot be sure who will lose or regain response. At the moment we don’t have a biomarker to tell us what we should do in our daily practice.”

Dr. Thaçi reported serving as an adviser to and paid investigator for Almirall, the study sponsor, and approximately 20 other pharmaceutical companies.

bjancin@mdedge.com

Not all chronic systemic inflammatory diseases are equal enhancers of atherosclerotic cardiovascular disease risk, according to a large case-control study.  

Current AHA/American College of Cardiology guidelines cite three chronic inflammatory diseases as atherosclerotic cardiovascular disease risk enhancers: rheumatoid arthritis, psoriasis, and HIV infection. But this study of those three diseases, along with three others marked by elevated high sensitivity C-reactive protein (systemic sclerosis, inflammatory bowel disease, and systemic lupus erythematosus [SLE]), showed that chronic inflammatory diseases are not monolithic in terms of their associated risk of incident coronary heart disease (CHD).

Indeed, two of the six inflammatory diseases – psoriasis and inflammatory bowel disease – turned out to be not at all associated with increased cardiovascular risk in the 37,117-patient study. The highest-risk disease was SLE, not specifically mentioned in the guidelines, Arjun Sinha, MD, a cardiology fellow at Northwestern University, Chicago, noted in his presentation at the virtual American Heart Association scientific sessions. 

The study included 18,129 patients with one of the six chronic inflammatory diseases and 18,988 matched controls, none with CHD at baseline. All regularly received outpatient care at Northwestern during 2000-2019. There were 1,011 incident CHD events during a median of 3.5 years of follow-up. 

In a Cox proportional hazards analysis adjusted for demographics, insurance status, hypertension, diabetes, current smoking, total cholesterol, and estimated glomerular filtration rate, here’s how the chronic inflammatory diseases stacked up in terms of incident CHD and MI risks: 

• SLE: hazard ratio for CHD, 2.85; for MI, 4.76.
• Systemic sclerosis: HR for CHD, 2.14; for MI, 3.19.
• HIV: HR for CHD, 1.38; for MI, 1.69.
• Rheumatoid arthritis: HR for CHD, 1.22; for MI, 1.45.
• Psoriasis: no significant increase.
• Inflammatory bowel disease: no significant increase.

In an exploratory analysis, Dr. Sinha and coinvestigators evaluated the risk of incident CHD stratified by disease severity. For lack of standardized disease severity scales, the investigators relied upon tertiles of CD4 T cell count in the HIV group and CRP in the others. The HR for new-onset CHD in the more than 5,000 patients with psoriasis didn’t vary by CRP tertile. However, there was a nonsignificant trend for greater disease severity, as reflected by CRP tertile, to be associated with increased incident CHD risk in the HIV and inflammatory bowel disease groups. 

In contrast, patients with rheumatoid arthritis or systemic sclerosis who were in the top CRP tertile had a significantly greater risk of developing CHD than that of controls, with HRs of 2.11 in the rheumatoid arthritis group and 4.59 with systemic sclerosis, although patients in the other two tertiles weren’t at significantly increased risk. But all three tertiles of CRP in patients with SLE were associated with significantly increased CHD risk: 3.17-fold in the lowest tertile of lupus severity, 5.38-fold in the middle tertile, and 4.04-fold in the top tertile for inflammation. 

These findings could be used in clinical practice to fine-tune atherosclerotic cardiovascular disease risk assessment based upon chronic inflammatory disease type and severity. That’s information which in turn can help guide the timing and intensity of preventive therapy for patients with each disease type. 

But studying the association between chronic systemic inflammatory diseases and CHD risk can be useful in additional ways, according to Dr. Sinha. These inflammatory diseases can serve as models of atherosclerosis that shed light on the non–lipid-related mechanisms involved in cardiovascular disease. 

“The gradient in risk may be hypothesis-generating with respect to which specific inflammatory pathways may contribute to CHD,” he explained. 

Each of these six chronic inflammatory diseases is characterized by a different form of major immune dysfunction, Dr. Sinha continued. A case in point is SLE, the inflammatory disease associated with the highest risk of CHD and MI. Lupus is characterized by a form of neutrophil dysfunction marked by increased formation and reduced degradation of neutrophil extracellular traps, or NETs, as well as by an increase in autoreactive B cells and dysfunctional CD4+ T helper cells. The increase in NETs of of particular interest because NETs have also been shown to contribute to the development of atherosclerosis, endothelial dysfunction, plaque erosion, and thrombosis. 

In another exploratory analysis, Dr. Sinha and coworkers found that SLE patients with a neutrophil count above the median level were twice as likely to develop CHD than were those with a neutrophil count below the median. 

A better understanding of the upstream pathways linking NET formation in SLE and atherosclerosis could lead to development of new or repurposed medications that target immune dysfunction in order to curb atherosclerosis, said Dr. Sinha, whose study won the AHA’s Samuel A. Levine Early Career Clinical Investigator Award. 

He reported having no financial conflicts regarding his study. 

bjancin@mdedge.com 

Not all chronic systemic inflammatory diseases are equal enhancers of atherosclerotic cardiovascular disease risk, according to a large case-control study.  

Current AHA/American College of Cardiology guidelines cite three chronic inflammatory diseases as atherosclerotic cardiovascular disease risk enhancers: rheumatoid arthritis, psoriasis, and HIV infection. But this study of those three diseases, along with three others marked by elevated high sensitivity C-reactive protein (systemic sclerosis, inflammatory bowel disease, and systemic lupus erythematosus [SLE]), showed that chronic inflammatory diseases are not monolithic in terms of their associated risk of incident coronary heart disease (CHD).

Indeed, two of the six inflammatory diseases – psoriasis and inflammatory bowel disease – turned out to be not at all associated with increased cardiovascular risk in the 37,117-patient study. The highest-risk disease was SLE, not specifically mentioned in the guidelines, Arjun Sinha, MD, a cardiology fellow at Northwestern University, Chicago, noted in his presentation at the virtual American Heart Association scientific sessions. 

The study included 18,129 patients with one of the six chronic inflammatory diseases and 18,988 matched controls, none with CHD at baseline. All regularly received outpatient care at Northwestern during 2000-2019. There were 1,011 incident CHD events during a median of 3.5 years of follow-up. 

In a Cox proportional hazards analysis adjusted for demographics, insurance status, hypertension, diabetes, current smoking, total cholesterol, and estimated glomerular filtration rate, here’s how the chronic inflammatory diseases stacked up in terms of incident CHD and MI risks: 

• SLE: hazard ratio for CHD, 2.85; for MI, 4.76.
• Systemic sclerosis: HR for CHD, 2.14; for MI, 3.19.
• HIV: HR for CHD, 1.38; for MI, 1.69.
• Rheumatoid arthritis: HR for CHD, 1.22; for MI, 1.45.
• Psoriasis: no significant increase.
• Inflammatory bowel disease: no significant increase.

In an exploratory analysis, Dr. Sinha and coinvestigators evaluated the risk of incident CHD stratified by disease severity. For lack of standardized disease severity scales, the investigators relied upon tertiles of CD4 T cell count in the HIV group and CRP in the others. The HR for new-onset CHD in the more than 5,000 patients with psoriasis didn’t vary by CRP tertile. However, there was a nonsignificant trend for greater disease severity, as reflected by CRP tertile, to be associated with increased incident CHD risk in the HIV and inflammatory bowel disease groups. 

In contrast, patients with rheumatoid arthritis or systemic sclerosis who were in the top CRP tertile had a significantly greater risk of developing CHD than that of controls, with HRs of 2.11 in the rheumatoid arthritis group and 4.59 with systemic sclerosis, although patients in the other two tertiles weren’t at significantly increased risk. But all three tertiles of CRP in patients with SLE were associated with significantly increased CHD risk: 3.17-fold in the lowest tertile of lupus severity, 5.38-fold in the middle tertile, and 4.04-fold in the top tertile for inflammation. 

These findings could be used in clinical practice to fine-tune atherosclerotic cardiovascular disease risk assessment based upon chronic inflammatory disease type and severity. That’s information which in turn can help guide the timing and intensity of preventive therapy for patients with each disease type. 

But studying the association between chronic systemic inflammatory diseases and CHD risk can be useful in additional ways, according to Dr. Sinha. These inflammatory diseases can serve as models of atherosclerosis that shed light on the non–lipid-related mechanisms involved in cardiovascular disease. 

“The gradient in risk may be hypothesis-generating with respect to which specific inflammatory pathways may contribute to CHD,” he explained. 

Each of these six chronic inflammatory diseases is characterized by a different form of major immune dysfunction, Dr. Sinha continued. A case in point is SLE, the inflammatory disease associated with the highest risk of CHD and MI. Lupus is characterized by a form of neutrophil dysfunction marked by increased formation and reduced degradation of neutrophil extracellular traps, or NETs, as well as by an increase in autoreactive B cells and dysfunctional CD4+ T helper cells. The increase in NETs of of particular interest because NETs have also been shown to contribute to the development of atherosclerosis, endothelial dysfunction, plaque erosion, and thrombosis. 

In another exploratory analysis, Dr. Sinha and coworkers found that SLE patients with a neutrophil count above the median level were twice as likely to develop CHD than were those with a neutrophil count below the median. 

A better understanding of the upstream pathways linking NET formation in SLE and atherosclerosis could lead to development of new or repurposed medications that target immune dysfunction in order to curb atherosclerosis, said Dr. Sinha, whose study won the AHA’s Samuel A. Levine Early Career Clinical Investigator Award. 

He reported having no financial conflicts regarding his study. 

bjancin@mdedge.com 

Not all chronic systemic inflammatory diseases are equal enhancers of atherosclerotic cardiovascular disease risk, according to a large case-control study.  

Current AHA/American College of Cardiology guidelines cite three chronic inflammatory diseases as atherosclerotic cardiovascular disease risk enhancers: rheumatoid arthritis, psoriasis, and HIV infection. But this study of those three diseases, along with three others marked by elevated high sensitivity C-reactive protein (systemic sclerosis, inflammatory bowel disease, and systemic lupus erythematosus [SLE]), showed that chronic inflammatory diseases are not monolithic in terms of their associated risk of incident coronary heart disease (CHD).

Indeed, two of the six inflammatory diseases – psoriasis and inflammatory bowel disease – turned out to be not at all associated with increased cardiovascular risk in the 37,117-patient study. The highest-risk disease was SLE, not specifically mentioned in the guidelines, Arjun Sinha, MD, a cardiology fellow at Northwestern University, Chicago, noted in his presentation at the virtual American Heart Association scientific sessions. 

The study included 18,129 patients with one of the six chronic inflammatory diseases and 18,988 matched controls, none with CHD at baseline. All regularly received outpatient care at Northwestern during 2000-2019. There were 1,011 incident CHD events during a median of 3.5 years of follow-up. 

In a Cox proportional hazards analysis adjusted for demographics, insurance status, hypertension, diabetes, current smoking, total cholesterol, and estimated glomerular filtration rate, here’s how the chronic inflammatory diseases stacked up in terms of incident CHD and MI risks: 

• SLE: hazard ratio for CHD, 2.85; for MI, 4.76.
• Systemic sclerosis: HR for CHD, 2.14; for MI, 3.19.
• HIV: HR for CHD, 1.38; for MI, 1.69.
• Rheumatoid arthritis: HR for CHD, 1.22; for MI, 1.45.
• Psoriasis: no significant increase.
• Inflammatory bowel disease: no significant increase.

In an exploratory analysis, Dr. Sinha and coinvestigators evaluated the risk of incident CHD stratified by disease severity. For lack of standardized disease severity scales, the investigators relied upon tertiles of CD4 T cell count in the HIV group and CRP in the others. The HR for new-onset CHD in the more than 5,000 patients with psoriasis didn’t vary by CRP tertile. However, there was a nonsignificant trend for greater disease severity, as reflected by CRP tertile, to be associated with increased incident CHD risk in the HIV and inflammatory bowel disease groups. 

In contrast, patients with rheumatoid arthritis or systemic sclerosis who were in the top CRP tertile had a significantly greater risk of developing CHD than that of controls, with HRs of 2.11 in the rheumatoid arthritis group and 4.59 with systemic sclerosis, although patients in the other two tertiles weren’t at significantly increased risk. But all three tertiles of CRP in patients with SLE were associated with significantly increased CHD risk: 3.17-fold in the lowest tertile of lupus severity, 5.38-fold in the middle tertile, and 4.04-fold in the top tertile for inflammation. 

These findings could be used in clinical practice to fine-tune atherosclerotic cardiovascular disease risk assessment based upon chronic inflammatory disease type and severity. That’s information which in turn can help guide the timing and intensity of preventive therapy for patients with each disease type. 

But studying the association between chronic systemic inflammatory diseases and CHD risk can be useful in additional ways, according to Dr. Sinha. These inflammatory diseases can serve as models of atherosclerosis that shed light on the non–lipid-related mechanisms involved in cardiovascular disease. 

“The gradient in risk may be hypothesis-generating with respect to which specific inflammatory pathways may contribute to CHD,” he explained. 

Each of these six chronic inflammatory diseases is characterized by a different form of major immune dysfunction, Dr. Sinha continued. A case in point is SLE, the inflammatory disease associated with the highest risk of CHD and MI. Lupus is characterized by a form of neutrophil dysfunction marked by increased formation and reduced degradation of neutrophil extracellular traps, or NETs, as well as by an increase in autoreactive B cells and dysfunctional CD4+ T helper cells. The increase in NETs of of particular interest because NETs have also been shown to contribute to the development of atherosclerosis, endothelial dysfunction, plaque erosion, and thrombosis. 

In another exploratory analysis, Dr. Sinha and coworkers found that SLE patients with a neutrophil count above the median level were twice as likely to develop CHD than were those with a neutrophil count below the median. 

A better understanding of the upstream pathways linking NET formation in SLE and atherosclerosis could lead to development of new or repurposed medications that target immune dysfunction in order to curb atherosclerosis, said Dr. Sinha, whose study won the AHA’s Samuel A. Levine Early Career Clinical Investigator Award. 

He reported having no financial conflicts regarding his study. 

bjancin@mdedge.com 

People taking even low-dose methotrexate need tuberculosis screening and ongoing clinical care if they live in areas where TB is common, results of a study presented at the virtual annual meeting of the American College of Rheumatology suggest.

Coauthor Carol Hitchon, MD, MSc, a rheumatologist with the University of Manitoba in Winnipeg, who presented the findings, warned that methotrexate (MTX) users who also take corticosteroids or other immunosuppressants are at particular risk and need TB screening.

Current management guidelines for rheumatic disease address TB in relation to biologics, but not in relation to methotrexate, Dr. Hitchon said.

“We know that methotrexate is the foundational DMARD [disease-modifying antirheumatic drug] for many rheumatic diseases, especially rheumatoid arthritis,” Dr. Hitchon noted at a press conference. “It’s safe and effective when dosed properly. However, methotrexate does have the potential for significant liver toxicity as well as infection, particularly for infectious organisms that are targeted by cell-mediated immunity, and TB is one of those agents.”

Using multiple databases, researchers conducted a systematic review of the literature published from 1990 to 2018 on TB rates among people who take less than 30 mg of methotrexate a week. Of the 4,700 studies they examined, 31 fit the criteria for this analysis.

They collected data on tuberculosis incidence or new TB diagnoses vs. reactivation of latent TB infection as well as TB outcomes, such as pulmonary symptoms, dissemination, and mortality.

They found a modest increase in the risk of TB infections in the setting of low-dose methotrexate. In addition, rates of TB in people with rheumatic disease who are treated with either methotrexate or biologics are generally higher than in the general population.

They also found that methotrexate users had higher rates of the type of TB that spreads beyond a patient’s lungs, compared with the general population.

Safety of INH with methotrexate

Researchers also looked at the safety of isoniazid (INH), the antibiotic used to treat TB, and found that isoniazid-related liver toxicity and neutropenia were more common when people took the antibiotic along with methotrexate, but those effects were usually reversible.

TB is endemic in various regions around the world. Historically there hasn’t been much rheumatology capacity in many of these areas, but as that capacity increases more people who are at high risk for developing or reactivating TB will be receiving methotrexate for rheumatic diseases, Dr. Hitchon said.

“It’s prudent for people managing patients who may be at higher risk for TB either from where they live or from where they travel that we should have a high suspicion for TB and consider screening as part of our workup in the course of initiating treatment like methotrexate,” she said.

Narender Annapureddy, MD, a rheumatologist at Vanderbilt University, Nashville, Tenn., who was not involved in the research, pointed out that a limitation of the work is that only 27% of the studies are from developing countries, which are more likely to have endemic TB, and those studies had very few cases.

“This finding needs to be studied in larger populations in TB-endemic areas and in high-risk populations,” he said in an interview.

As for practice implications in the United States, Dr. Annapureddy noted that TB is rare in the United States and most of the cases occur in people born in other countries.

“This population may be at risk for TB and should probably be screened for TB before initiating methotrexate,” he said. “Since biologics are usually the next step, especially in RA after patients fail methotrexate, having information on TB status may also help guide management options after MTX failure.

“Since high-dose steroids are another important risk factor for TB activation,” Dr. Annapureddy continued, “rheumatologists should likely consider screening patients who are going to be on moderate to high doses of steroids with MTX.”

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

People taking even low-dose methotrexate need tuberculosis screening and ongoing clinical care if they live in areas where TB is common, results of a study presented at the virtual annual meeting of the American College of Rheumatology suggest.

Coauthor Carol Hitchon, MD, MSc, a rheumatologist with the University of Manitoba in Winnipeg, who presented the findings, warned that methotrexate (MTX) users who also take corticosteroids or other immunosuppressants are at particular risk and need TB screening.

Current management guidelines for rheumatic disease address TB in relation to biologics, but not in relation to methotrexate, Dr. Hitchon said.

“We know that methotrexate is the foundational DMARD [disease-modifying antirheumatic drug] for many rheumatic diseases, especially rheumatoid arthritis,” Dr. Hitchon noted at a press conference. “It’s safe and effective when dosed properly. However, methotrexate does have the potential for significant liver toxicity as well as infection, particularly for infectious organisms that are targeted by cell-mediated immunity, and TB is one of those agents.”

Using multiple databases, researchers conducted a systematic review of the literature published from 1990 to 2018 on TB rates among people who take less than 30 mg of methotrexate a week. Of the 4,700 studies they examined, 31 fit the criteria for this analysis.

They collected data on tuberculosis incidence or new TB diagnoses vs. reactivation of latent TB infection as well as TB outcomes, such as pulmonary symptoms, dissemination, and mortality.

They found a modest increase in the risk of TB infections in the setting of low-dose methotrexate. In addition, rates of TB in people with rheumatic disease who are treated with either methotrexate or biologics are generally higher than in the general population.

They also found that methotrexate users had higher rates of the type of TB that spreads beyond a patient’s lungs, compared with the general population.

Safety of INH with methotrexate

Researchers also looked at the safety of isoniazid (INH), the antibiotic used to treat TB, and found that isoniazid-related liver toxicity and neutropenia were more common when people took the antibiotic along with methotrexate, but those effects were usually reversible.

TB is endemic in various regions around the world. Historically there hasn’t been much rheumatology capacity in many of these areas, but as that capacity increases more people who are at high risk for developing or reactivating TB will be receiving methotrexate for rheumatic diseases, Dr. Hitchon said.

“It’s prudent for people managing patients who may be at higher risk for TB either from where they live or from where they travel that we should have a high suspicion for TB and consider screening as part of our workup in the course of initiating treatment like methotrexate,” she said.

Narender Annapureddy, MD, a rheumatologist at Vanderbilt University, Nashville, Tenn., who was not involved in the research, pointed out that a limitation of the work is that only 27% of the studies are from developing countries, which are more likely to have endemic TB, and those studies had very few cases.

“This finding needs to be studied in larger populations in TB-endemic areas and in high-risk populations,” he said in an interview.

As for practice implications in the United States, Dr. Annapureddy noted that TB is rare in the United States and most of the cases occur in people born in other countries.

“This population may be at risk for TB and should probably be screened for TB before initiating methotrexate,” he said. “Since biologics are usually the next step, especially in RA after patients fail methotrexate, having information on TB status may also help guide management options after MTX failure.

“Since high-dose steroids are another important risk factor for TB activation,” Dr. Annapureddy continued, “rheumatologists should likely consider screening patients who are going to be on moderate to high doses of steroids with MTX.”

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

People taking even low-dose methotrexate need tuberculosis screening and ongoing clinical care if they live in areas where TB is common, results of a study presented at the virtual annual meeting of the American College of Rheumatology suggest.

Coauthor Carol Hitchon, MD, MSc, a rheumatologist with the University of Manitoba in Winnipeg, who presented the findings, warned that methotrexate (MTX) users who also take corticosteroids or other immunosuppressants are at particular risk and need TB screening.

Current management guidelines for rheumatic disease address TB in relation to biologics, but not in relation to methotrexate, Dr. Hitchon said.

“We know that methotrexate is the foundational DMARD [disease-modifying antirheumatic drug] for many rheumatic diseases, especially rheumatoid arthritis,” Dr. Hitchon noted at a press conference. “It’s safe and effective when dosed properly. However, methotrexate does have the potential for significant liver toxicity as well as infection, particularly for infectious organisms that are targeted by cell-mediated immunity, and TB is one of those agents.”

Using multiple databases, researchers conducted a systematic review of the literature published from 1990 to 2018 on TB rates among people who take less than 30 mg of methotrexate a week. Of the 4,700 studies they examined, 31 fit the criteria for this analysis.

They collected data on tuberculosis incidence or new TB diagnoses vs. reactivation of latent TB infection as well as TB outcomes, such as pulmonary symptoms, dissemination, and mortality.

They found a modest increase in the risk of TB infections in the setting of low-dose methotrexate. In addition, rates of TB in people with rheumatic disease who are treated with either methotrexate or biologics are generally higher than in the general population.

They also found that methotrexate users had higher rates of the type of TB that spreads beyond a patient’s lungs, compared with the general population.

Safety of INH with methotrexate

Researchers also looked at the safety of isoniazid (INH), the antibiotic used to treat TB, and found that isoniazid-related liver toxicity and neutropenia were more common when people took the antibiotic along with methotrexate, but those effects were usually reversible.

TB is endemic in various regions around the world. Historically there hasn’t been much rheumatology capacity in many of these areas, but as that capacity increases more people who are at high risk for developing or reactivating TB will be receiving methotrexate for rheumatic diseases, Dr. Hitchon said.

“It’s prudent for people managing patients who may be at higher risk for TB either from where they live or from where they travel that we should have a high suspicion for TB and consider screening as part of our workup in the course of initiating treatment like methotrexate,” she said.

Narender Annapureddy, MD, a rheumatologist at Vanderbilt University, Nashville, Tenn., who was not involved in the research, pointed out that a limitation of the work is that only 27% of the studies are from developing countries, which are more likely to have endemic TB, and those studies had very few cases.

“This finding needs to be studied in larger populations in TB-endemic areas and in high-risk populations,” he said in an interview.

As for practice implications in the United States, Dr. Annapureddy noted that TB is rare in the United States and most of the cases occur in people born in other countries.

“This population may be at risk for TB and should probably be screened for TB before initiating methotrexate,” he said. “Since biologics are usually the next step, especially in RA after patients fail methotrexate, having information on TB status may also help guide management options after MTX failure.

“Since high-dose steroids are another important risk factor for TB activation,” Dr. Annapureddy continued, “rheumatologists should likely consider screening patients who are going to be on moderate to high doses of steroids with MTX.”

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

Tapinarof cream 1% applied once daily in patients with plaque psoriasis convincingly hit its primary and secondary endpoints and was well tolerated in two identical pivotal phase 3, randomized trials, Mark G. Lebwohl, MD, reported at the virtual annual congress of the European Academy of Dermatology and Venereology.

“Tapinarof cream has the potential to be a first-in-class topical therapeutic aryl hydrocarbon receptor modulating agent and will provide physicians and patients with a novel nonsteroidal topical treatment option that’s effective and well tolerated,” predicted Dr. Lebwohl, professor and chair of the department of dermatology at the Icahn School of Medicine at Mount Sinai, New York.

Dermavant Sciences, the company developing topical tapinarof for treatment of atopic dermatitis as well as psoriasis, announced that upon completion of an ongoing long-term extension study the company plans to file for approval of the drug for psoriasis in 2021.

The two pivotal phase 3 trials, PSOARING 1 and PSOARING 2, randomized a total of 1,025 patients with plaque psoriasis to once-daily tapinarof cream 1% or its vehicle. “This was a fairly difficult group of patients,” Dr. Lebwohl said. Roughly 80% had moderate psoriasis as defined by a baseline Physician Global Assessment (PGA) score of 3, with the remainder split evenly between mild and severe disease. Participants averaged 8% body surface area involvement. Body mass index was on average greater than 31 kg/m².

The primary efficacy endpoint was a PGA score of 0 or 1 – that is, clear or almost clear – plus at least a 2-grade improvement in PGA from baseline at week 12. This was achieved in 35.4% of patients on tapinarof cream once daily in PSOARING 1 and 40.2% in PSOARING 2, compared with 6.0% and 6.3% of vehicle-treated controls, a highly significant difference (both P < .0001).

The prespecified secondary endpoint was a 75% improvement in Psoriasis Area and Severity Index (PASI) score from baseline to week 12. The PASI 75 rates were 36.1% and 47.6% with tapinarof, significantly better than the 10.2% and 6.9% rates in controls.

The most common adverse event associated with tapinarof was folliculitis, which occurred in 20.6% of treated patients in PSOARING 1 and in 15.7% in PSOARING 2. More than 98% of cases were mild or moderate. The folliculitis led to study discontinuation in only 1.8% and 0.9% of subjects in the two trials.

The other noteworthy adverse event was contact dermatitis. It occurred in 3.8% and 4.7% of tapinarof-treated patients, again with low study discontinuation rates of 1.5% and 2.2%.

During the audience discussion, Linda Stein Gold, MD, lead investigator for PSOARING 2, was asked about this folliculitis. She said the mechanism is unclear, as is the best management. She encountered it in patients, didn’t treat it, and it went away on its own. It’s not a bacterial folliculitis; when cultured it invariably proved culture negative, she noted.

The comparative efficacy of tapinarof cream versus the potent and superpotent topical corticosteroids commonly used in the treatment of psoriasis hasn’t been evaluated in head-to-head studies. Her experience and that of the other investigators has been that tapinarof’s efficacy is comparably strong, “but we don’t have the steroid side effects,” said Dr. Stein Gold, director of dermatology clinical research at Henry Ford Health System in Detroit.

In an interview, Dr. Lebwohl said tapinarof, if approved, could help meet a major unmet need for new and better topical therapies for psoriasis.

“You keep hearing about all these biologic agents and small-molecule pills coming out, but the majority of patients still only need topical therapy,” he observed.

Moreover, even when patients with more severe disease achieve a PASI 75 or PASI 90 response with systemic therapy, they usually still need supplemental topical therapy to get them closer to the goal of clear skin.

The superpotent steroids that are the current mainstay of topical therapy come with predictable side effects that dictate a 2- to 4-week limit on their approved use. Also, they’re not supposed to be applied to the face or to intertriginous sites, including the groin, axillae, and under the breasts. In contrast, tapinarof has proved safe and effective in these sensitive areas.

Asked to predict how tapinarof is likely to be used in clinical practice, Dr. Lebwohl replied: “The efficacy was equivalent to strong topical steroids, so I think it could be used first line in place of topical steroids. And in particular, in patients with psoriasis at facial and intertriginous sites, I think an argument can be made for insisting that it be first line.”

He also expects that physicians will end up utilizing tapinarof for a varied group of steroid-responsive dermatoses beyond psoriasis and atopic dermatitis.

“It clearly reduces inflammation, which is why I would expect it would work well for those,” the dermatologist said.

The mechanism of action of tapinarof has been worked out. The drug enters the cell and binds to the aryl hydrocarbon receptor, forming a complex that enters the nucleus. There it joins with the aryl hydrocarbon receptor nuclear translocator, which regulates gene expression so as to reduce production of inflammatory cytokines while promoting an increase in skin barrier proteins, which is why tapinarof is also being developed as an atopic dermatitis therapy.

Dr. Lebwohl and Dr. Stein Gold reported receiving research funds from and serving as consultants to Dermavant Sciences as well as numerous other pharmaceutical companies.

bjancin@mdedge.com

Tapinarof cream 1% applied once daily in patients with plaque psoriasis convincingly hit its primary and secondary endpoints and was well tolerated in two identical pivotal phase 3, randomized trials, Mark G. Lebwohl, MD, reported at the virtual annual congress of the European Academy of Dermatology and Venereology.

“Tapinarof cream has the potential to be a first-in-class topical therapeutic aryl hydrocarbon receptor modulating agent and will provide physicians and patients with a novel nonsteroidal topical treatment option that’s effective and well tolerated,” predicted Dr. Lebwohl, professor and chair of the department of dermatology at the Icahn School of Medicine at Mount Sinai, New York.

Dermavant Sciences, the company developing topical tapinarof for treatment of atopic dermatitis as well as psoriasis, announced that upon completion of an ongoing long-term extension study the company plans to file for approval of the drug for psoriasis in 2021.

The two pivotal phase 3 trials, PSOARING 1 and PSOARING 2, randomized a total of 1,025 patients with plaque psoriasis to once-daily tapinarof cream 1% or its vehicle. “This was a fairly difficult group of patients,” Dr. Lebwohl said. Roughly 80% had moderate psoriasis as defined by a baseline Physician Global Assessment (PGA) score of 3, with the remainder split evenly between mild and severe disease. Participants averaged 8% body surface area involvement. Body mass index was on average greater than 31 kg/m².

The primary efficacy endpoint was a PGA score of 0 or 1 – that is, clear or almost clear – plus at least a 2-grade improvement in PGA from baseline at week 12. This was achieved in 35.4% of patients on tapinarof cream once daily in PSOARING 1 and 40.2% in PSOARING 2, compared with 6.0% and 6.3% of vehicle-treated controls, a highly significant difference (both P < .0001).

The prespecified secondary endpoint was a 75% improvement in Psoriasis Area and Severity Index (PASI) score from baseline to week 12. The PASI 75 rates were 36.1% and 47.6% with tapinarof, significantly better than the 10.2% and 6.9% rates in controls.

The most common adverse event associated with tapinarof was folliculitis, which occurred in 20.6% of treated patients in PSOARING 1 and in 15.7% in PSOARING 2. More than 98% of cases were mild or moderate. The folliculitis led to study discontinuation in only 1.8% and 0.9% of subjects in the two trials.

The other noteworthy adverse event was contact dermatitis. It occurred in 3.8% and 4.7% of tapinarof-treated patients, again with low study discontinuation rates of 1.5% and 2.2%.

During the audience discussion, Linda Stein Gold, MD, lead investigator for PSOARING 2, was asked about this folliculitis. She said the mechanism is unclear, as is the best management. She encountered it in patients, didn’t treat it, and it went away on its own. It’s not a bacterial folliculitis; when cultured it invariably proved culture negative, she noted.

The comparative efficacy of tapinarof cream versus the potent and superpotent topical corticosteroids commonly used in the treatment of psoriasis hasn’t been evaluated in head-to-head studies. Her experience and that of the other investigators has been that tapinarof’s efficacy is comparably strong, “but we don’t have the steroid side effects,” said Dr. Stein Gold, director of dermatology clinical research at Henry Ford Health System in Detroit.

In an interview, Dr. Lebwohl said tapinarof, if approved, could help meet a major unmet need for new and better topical therapies for psoriasis.

“You keep hearing about all these biologic agents and small-molecule pills coming out, but the majority of patients still only need topical therapy,” he observed.

Moreover, even when patients with more severe disease achieve a PASI 75 or PASI 90 response with systemic therapy, they usually still need supplemental topical therapy to get them closer to the goal of clear skin.

The superpotent steroids that are the current mainstay of topical therapy come with predictable side effects that dictate a 2- to 4-week limit on their approved use. Also, they’re not supposed to be applied to the face or to intertriginous sites, including the groin, axillae, and under the breasts. In contrast, tapinarof has proved safe and effective in these sensitive areas.

Asked to predict how tapinarof is likely to be used in clinical practice, Dr. Lebwohl replied: “The efficacy was equivalent to strong topical steroids, so I think it could be used first line in place of topical steroids. And in particular, in patients with psoriasis at facial and intertriginous sites, I think an argument can be made for insisting that it be first line.”

He also expects that physicians will end up utilizing tapinarof for a varied group of steroid-responsive dermatoses beyond psoriasis and atopic dermatitis.

“It clearly reduces inflammation, which is why I would expect it would work well for those,” the dermatologist said.

The mechanism of action of tapinarof has been worked out. The drug enters the cell and binds to the aryl hydrocarbon receptor, forming a complex that enters the nucleus. There it joins with the aryl hydrocarbon receptor nuclear translocator, which regulates gene expression so as to reduce production of inflammatory cytokines while promoting an increase in skin barrier proteins, which is why tapinarof is also being developed as an atopic dermatitis therapy.

Dr. Lebwohl and Dr. Stein Gold reported receiving research funds from and serving as consultants to Dermavant Sciences as well as numerous other pharmaceutical companies.

bjancin@mdedge.com

Tapinarof cream 1% applied once daily in patients with plaque psoriasis convincingly hit its primary and secondary endpoints and was well tolerated in two identical pivotal phase 3, randomized trials, Mark G. Lebwohl, MD, reported at the virtual annual congress of the European Academy of Dermatology and Venereology.

“Tapinarof cream has the potential to be a first-in-class topical therapeutic aryl hydrocarbon receptor modulating agent and will provide physicians and patients with a novel nonsteroidal topical treatment option that’s effective and well tolerated,” predicted Dr. Lebwohl, professor and chair of the department of dermatology at the Icahn School of Medicine at Mount Sinai, New York.

Dermavant Sciences, the company developing topical tapinarof for treatment of atopic dermatitis as well as psoriasis, announced that upon completion of an ongoing long-term extension study the company plans to file for approval of the drug for psoriasis in 2021.

The two pivotal phase 3 trials, PSOARING 1 and PSOARING 2, randomized a total of 1,025 patients with plaque psoriasis to once-daily tapinarof cream 1% or its vehicle. “This was a fairly difficult group of patients,” Dr. Lebwohl said. Roughly 80% had moderate psoriasis as defined by a baseline Physician Global Assessment (PGA) score of 3, with the remainder split evenly between mild and severe disease. Participants averaged 8% body surface area involvement. Body mass index was on average greater than 31 kg/m².

The primary efficacy endpoint was a PGA score of 0 or 1 – that is, clear or almost clear – plus at least a 2-grade improvement in PGA from baseline at week 12. This was achieved in 35.4% of patients on tapinarof cream once daily in PSOARING 1 and 40.2% in PSOARING 2, compared with 6.0% and 6.3% of vehicle-treated controls, a highly significant difference (both P < .0001).

The prespecified secondary endpoint was a 75% improvement in Psoriasis Area and Severity Index (PASI) score from baseline to week 12. The PASI 75 rates were 36.1% and 47.6% with tapinarof, significantly better than the 10.2% and 6.9% rates in controls.

The most common adverse event associated with tapinarof was folliculitis, which occurred in 20.6% of treated patients in PSOARING 1 and in 15.7% in PSOARING 2. More than 98% of cases were mild or moderate. The folliculitis led to study discontinuation in only 1.8% and 0.9% of subjects in the two trials.

The other noteworthy adverse event was contact dermatitis. It occurred in 3.8% and 4.7% of tapinarof-treated patients, again with low study discontinuation rates of 1.5% and 2.2%.

During the audience discussion, Linda Stein Gold, MD, lead investigator for PSOARING 2, was asked about this folliculitis. She said the mechanism is unclear, as is the best management. She encountered it in patients, didn’t treat it, and it went away on its own. It’s not a bacterial folliculitis; when cultured it invariably proved culture negative, she noted.

The comparative efficacy of tapinarof cream versus the potent and superpotent topical corticosteroids commonly used in the treatment of psoriasis hasn’t been evaluated in head-to-head studies. Her experience and that of the other investigators has been that tapinarof’s efficacy is comparably strong, “but we don’t have the steroid side effects,” said Dr. Stein Gold, director of dermatology clinical research at Henry Ford Health System in Detroit.

In an interview, Dr. Lebwohl said tapinarof, if approved, could help meet a major unmet need for new and better topical therapies for psoriasis.

“You keep hearing about all these biologic agents and small-molecule pills coming out, but the majority of patients still only need topical therapy,” he observed.

Moreover, even when patients with more severe disease achieve a PASI 75 or PASI 90 response with systemic therapy, they usually still need supplemental topical therapy to get them closer to the goal of clear skin.

The superpotent steroids that are the current mainstay of topical therapy come with predictable side effects that dictate a 2- to 4-week limit on their approved use. Also, they’re not supposed to be applied to the face or to intertriginous sites, including the groin, axillae, and under the breasts. In contrast, tapinarof has proved safe and effective in these sensitive areas.

Asked to predict how tapinarof is likely to be used in clinical practice, Dr. Lebwohl replied: “The efficacy was equivalent to strong topical steroids, so I think it could be used first line in place of topical steroids. And in particular, in patients with psoriasis at facial and intertriginous sites, I think an argument can be made for insisting that it be first line.”

He also expects that physicians will end up utilizing tapinarof for a varied group of steroid-responsive dermatoses beyond psoriasis and atopic dermatitis.

“It clearly reduces inflammation, which is why I would expect it would work well for those,” the dermatologist said.

The mechanism of action of tapinarof has been worked out. The drug enters the cell and binds to the aryl hydrocarbon receptor, forming a complex that enters the nucleus. There it joins with the aryl hydrocarbon receptor nuclear translocator, which regulates gene expression so as to reduce production of inflammatory cytokines while promoting an increase in skin barrier proteins, which is why tapinarof is also being developed as an atopic dermatitis therapy.

Dr. Lebwohl and Dr. Stein Gold reported receiving research funds from and serving as consultants to Dermavant Sciences as well as numerous other pharmaceutical companies.

bjancin@mdedge.com

In November 2019, the American Academy of Dermatology (AAD) and the National Psoriasis Foundation (NPF) released their first set of recommendations for the management of pediatric psoriasis.¹ The pediatric guidelines discuss methods of quantifying disease severity in children, triggers and comorbidities, and the efficacy and safety of various therapeutic agents. This review aims to discuss, in a condensed form, special considerations unique to the management of children with psoriasis as presented in the guidelines as well as grade A– and grade B–level treatment recommendations (Table).

Quantifying Psoriasis Severity in Children

Percentage body surface area (BSA) involvement is the most common mode of grading psoriasis severity, with less than 3% BSA involvement being considered mild, 3% to 10% BSA moderate, and more than 10% severe disease. In children, the standard method of measuring BSA is the rule of 9’s: the head and each arm make up 9% of the total BSA, each leg and the front and back of the torso respectively each make up 18%, and the genitalia make up 1%. It also is important to consider impact on quality of life, which may be remarkable in spite of limited BSA involvement. The children’s dermatology life quality index score may be utilized in combination with affected BSA to determine the burden of psoriasis in context of impact on daily life. This metric is available in both written and cartoon form, and it consists of 10 questions that include variables such as severity of itch, impact on social life, and effects on sleep. Most notably, this tool incorporates pruritus,² which generally is addressed inadequately in pediatric psoriasis.

Triggers and Comorbidities in Pediatric Patients

In children, it is important to identify and eliminate modifiable factors that may prompt psoriasis flares. Infections, particularly group A beta-hemolytic streptococcal infections, are a major trigger in neonates and infants. Other exacerbating factors in children include emotional stress, secondhand cigarette smoke, Kawasaki disease, and withdrawal from systemic corticosteroids.

Psoriatic arthritis (PsA) is a burdensome comorbidity affecting children with psoriasis. The prevalence of joint disease is 15-times greater in children with psoriasis vs those without,³ and 80% of children with PsA develop rheumatologic symptoms, which typically include oligoarticular disease and dactylitis in infants and girls and enthesitis and axial joint involvement in boys and older children, years prior to the onset of cutaneous disease.⁴ Uveitis often occurs in children with psoriasis and PsA but not in those with isolated cutaneous disease.

Compared to unaffected children, pediatric patients with psoriasis have greater prevalence of metabolic and cardiovascular risk factors during childhood, including central obesity, hypertension, hypertriglyceridemia, hypercholesterolemia, insulin resistance, atherosclerosis, arrythmia, and valvular heart disease. Family history of obesity increases the risk for early-onset development of cutaneous lesions,^5,6 and weight reduction may alleviate severity of psoriasis lesions.⁷ In the United States, many of the metabolic associations observed are particularly robust in Black and Hispanic children vs those of other races. Furthermore, the prevalence of inflammatory bowel disease is 3- to 4-times higher in children with psoriasis compared to those without.

As with other cutaneous diseases, it is important to be aware of social and mental health concerns in children with psoriasis. The majority of pediatric patients with psoriasis experience name-calling, shaming, or bullying, and many have concerns from skin shedding and malodor. Independent risk for depression after the onset of psoriasis is high. Affected older children and adolescents are at increased risk for alcohol and drug abuse as well as eating disorders.

Despite these identified comorbidities, there are no unique screening recommendations for arthritis, ophthalmologic disease, metabolic disease, cardiovascular disease, gastrointestinal tract disease, or mental health issues in children with psoriasis. Rather, these patients should be monitored according to the American Academy of Pediatrics or American Diabetes Association guidelines for all pediatric patients.^8,9 Nonetheless, educating patients and guardians about these potential issues may be warranted.

Topical Therapies

For children with mild to moderate psoriasis, topical therapies are first line. Despite being off label, topical corticosteroids are the mainstay of therapy for localized psoriatic plaques in children. Topical vitamin D analogues—calcitriol and calcipotriol/calcipotriene—are highly effective and well tolerated, and they frequently are used in combination with topical corticosteroids. Topical calcineurin inhibitors, namely tacrolimus, also are used off label but are considered first line for sensitive regions of the skin in children, including the face, genitalia, and body folds. There currently is limited evidence for supporting the use of the topical vitamin A analogue tazarotene in children with psoriasis, though some consider its off-label use effective for pediatric nail psoriasis. It also may be used as an adjunct to topical corticosteroids to minimize irritation.

Although there is no gold standard topical regimen, combination therapy with a high-potency topical steroid and topical vitamin D analogue commonly is used to minimize steroid-induced side effects. For the first 2 weeks of treatment, they each may be applied once daily or mixed together and applied twice daily. For subsequent maintenance, topical calcipotriene may be applied on weekdays and topical steroids only on weekends. Combination calcipotriol–betamethasone dipropionate also is available as cream, ointment, foam, and suspension vehicles for use on the body and scalp in children aged 12 years and older. Tacrolimus ointment 0.1% may be applied in a thin layer up to twice daily. Concurrent emollient use also is recommended with these therapies.

Health care providers should educate patients and guardians about the potential side effects of topical therapies. They also should provide explicit instructions for amount, site, frequency, and duration of application. Topical corticosteroids commonly result in burning on application and may potentially cause skin thinning and striae with overuse. Topical vitamin D analogues may result in local irritation that may be improved by concurrent emollient use, and they generally should be avoided on sensitive sites. Topical calcineurin inhibitors are associated with burning, stinging, and pruritus, and the US Food and Drug Administration has issued a black-box warning related to risk for lymphoma with their chronic intermittent use. However, it was based on rare reports of lymphoma in transplant patients taking oral calcineurin inhibitors; no clinical trials to date in humans have demonstrated an increased risk for malignancy with topical calcineurin inhibitors.¹⁰ Tazarotene should be used cautiously in females of childbearing age given its teratogenic potential.

Children younger than 7 years are especially prone to suppression of the hypothalamic-pituitary-adrenal axis from topical corticosteroid therapy and theoretically hypercalcemia and hypervitaminosis D from topical vitamin D analogues, as their high BSA-to-volume ratio increases potential for systemic absorption. Children should avoid occlusive application of topical vitamin D analogues to large areas of the skin. Monitoring of vitamin D metabolites in the serum may be considered if calcipotriene or calcipotriol application to a large BSA is warranted.

Light-Based Therapy

In children with widespread psoriasis or those refractory to topical therapy, phototherapy may be considered. Narrowband UVB (311- to 313-nm wavelength) therapy is considered a first-line form of phototherapy in pediatric psoriasis. Mineral oil or emollient pretreatment to affected areas may augment the efficacy of UV-based treatments.¹¹ Excimer laser and UVA also may be efficacious, though evidence is limited in children. Treatment is recommended to start at 3 days a week, and once improvement is seen, the frequency can be decreased to 2 days a week. Once desired clearance is achieved, maintenance therapy can be continued at even longer intervals. Adjunctive use of tar preparations may potentiate the efficacy of phototherapy, though there is a theoretical increased risk for carcinogenicity with prolonged use of coal tar. Side effects of phototherapy include erythema, blistering hyperpigmentation, and pruritus. Psoralen is contraindicated in children younger than 12 years. All forms of phototherapy are contraindicated in children with generalized erythroderma and cutaneous cancer syndromes. Other important pediatric-specific considerations include anxiety that may be provoked by UV light machines and inconvenience of frequent appointments.

Nonbiologic Systemic Therapies

Systemic therapies may be considered in children with recalcitrant, widespread, or rapidly progressing psoriasis, particularly if the disease is accompanied by severe emotional and psychological burden. These drugs, which include methotrexate, cyclosporine, and acitretin (see eTable for recommended dosing), are advantageous in that they may be combined with other therapies; however, they have potential for dangerous toxicities.

Methotrexate is the most frequently utilized systemic therapy for psoriasis worldwide in children because of its low cost, once-weekly dosing, and the substantial amount of long-term efficacy and safety data available in the pediatric population. It is slow acting initially but has excellent long-term efficacy for nearly every subtype of psoriasis. The most common side effect of methotrexate is gastrointestinal tract intolerance. Nonetheless, adverse events are rare in children without prior history, with 1 large study (N=289) reporting no adverse events in more than 90% of patients aged 9 to 14 years treated with methotrexate.¹² Current guidelines recommend monitoring for bone marrow suppression and elevated transaminase levels 4 to 6 days after initiating treatment.¹ The absolute contraindications for methotrexate are pregnancy and liver disease, and caution should be taken in children with metabolic risk factors. Adolescents must be counseled regarding the elevated risk for hepatotoxicity associated with alcohol ingestion. Methotrexate therapy also requires 1 mg folic acid supplementation 6 to 7 days a week, which decreases the risk for developing folic acid deficiency and may decrease gastrointestinal tract intolerance and hepatic side effects that may result from therapy.

Cyclosporine is an effective and well-tolerated option for rapid control of severe psoriasis in children. It is useful for various types of psoriasis but generally is reserved for more severe subtypes, such as generalized pustular psoriasis, erythrodermic psoriasis, and uncontrolled plaque psoriasis. Long-term use of cyclosporine may result in renal toxicity and hypertension, and this therapy is absolutely contraindicated in children with kidney disease or hypertension at baseline. It is strongly recommended to evaluate blood pressure every week for the first month of therapy and at every subsequent follow-up visit, which may occur at variable intervals based on the judgement of the provider. Evaluation before and during treatment with cyclosporine also should include a complete blood cell count, complete metabolic panel, and lipid panel.

Systemic retinoids have a unique advantage over methotrexate and cyclosporine in that they are not immunosuppressive and therefore are not contraindicated in children who are very young or immunosuppressed. Children receiving systemic retinoids also can receive routine live vaccines—measles-mumps-rubella, varicella zoster, and rotavirus—that are contraindicated with other systemic therapies. Acitretin is particularly effective in pediatric patients with diffuse guttate psoriasis, pustular psoriasis, and palmoplantar psoriasis. Narrowband UVB therapy has been shown to augment the effectiveness of acitretin in children, which may allow for reduced acitretin dosing. Pustular psoriasis may respond as quickly as 3 weeks after initiation, whereas it may take 2 to 3 months before improvement is noticed in plaque psoriasis. Side effects of retinoids include skin dryness, hyperlipidemia, and gastrointestinal tract upset. The most severe long-term concern is skeletal toxicity, including premature epiphyseal closure, hyperostosis, periosteal bone formation, and decreased bone mineral density.¹ Vitamin A derivatives also are known teratogens and should be avoided in females of childbearing potential. Lipids and transaminases should be monitored routinely, and screening for depression and psychiatric symptoms should be performed frequently.¹

When utilizing systemic therapies, the objective should be to control the disease, maintain stability, and ultimately taper to the lowest effective dose or transition to a topical therapy, if feasible. Although no particular systemic therapy is recommended as first line for children with psoriasis, it is important to consider comorbidities, contraindications, monitoring frequency, mode of administration (injectable therapies elicit more psychological trauma in children than oral therapies), and expense when determining the best choice.

Biologics

Biologic agents are associated with very high to total psoriatic plaque clearance rates and require infrequent dosing and monitoring. However, their use may be limited by cost and injection phobias in children as well as limited evidence for their efficacy and safety in pediatric psoriasis. Several studies have established the safety and effectiveness of biologics in children with plaque psoriasis (see eTable for recommended dosing), whereas the evidence supporting their use in treating pustular and erythrodermic variants are limited to case reports and case series. The tumor necrosis factor α (TNF-α) inhibitor etanercept has been approved for use in children aged 4 years and older, and the IL-12/IL-23 inhibitor ustekinumab is approved in children aged 6 years and older. Other TNF-α inhibitors, namely infliximab and adalimumab, commonly are utilized off label for pediatric psoriasis. The most common side effect of biologic therapies in pediatric patients is injection-site reactions.¹ Prior to initiating therapy, children must undergo tuberculosis screening either by purified protein derivative testing or IFN-γ release assay. Testing should be repeated annually in individuals taking TNF-α inhibitors, though the utility of repeat testing when taking biologics in other classes is not clear. High-risk patients also should be screened for human immunodeficiency virus and hepatitis. Follow-up frequency may range from every 3 months to annually, based on judgement of the provider. In children who develop loss of response to biologics, methotrexate can be added to the regimen to attenuate formation of efficacy-reducing antidrug antibodies.

Final Thoughts

When managing children with psoriasis, it is important for dermatologists to appropriately educate guardians and children on the disease course, as well as consider the psychological, emotional, social, and financial factors that may direct decision-making regarding optimal therapeutics. Dermatologists should consider collaboration with the child’s primary care physician and other specialists to ensure that all needs are met.

These guidelines provide a framework agreed upon by numerous experts in pediatric psoriasis, but they are limited by gaps in the research. There still is much to be learned regarding the pathophysiology of psoriasis; the risk for developing comorbidities during adulthood; and the efficacy and safety of certain therapeutics, particularly biologics, in pediatric patients with psoriasis.

In November 2019, the American Academy of Dermatology (AAD) and the National Psoriasis Foundation (NPF) released their first set of recommendations for the management of pediatric psoriasis.¹ The pediatric guidelines discuss methods of quantifying disease severity in children, triggers and comorbidities, and the efficacy and safety of various therapeutic agents. This review aims to discuss, in a condensed form, special considerations unique to the management of children with psoriasis as presented in the guidelines as well as grade A– and grade B–level treatment recommendations (Table).

Quantifying Psoriasis Severity in Children

Percentage body surface area (BSA) involvement is the most common mode of grading psoriasis severity, with less than 3% BSA involvement being considered mild, 3% to 10% BSA moderate, and more than 10% severe disease. In children, the standard method of measuring BSA is the rule of 9’s: the head and each arm make up 9% of the total BSA, each leg and the front and back of the torso respectively each make up 18%, and the genitalia make up 1%. It also is important to consider impact on quality of life, which may be remarkable in spite of limited BSA involvement. The children’s dermatology life quality index score may be utilized in combination with affected BSA to determine the burden of psoriasis in context of impact on daily life. This metric is available in both written and cartoon form, and it consists of 10 questions that include variables such as severity of itch, impact on social life, and effects on sleep. Most notably, this tool incorporates pruritus,² which generally is addressed inadequately in pediatric psoriasis.

Triggers and Comorbidities in Pediatric Patients

In children, it is important to identify and eliminate modifiable factors that may prompt psoriasis flares. Infections, particularly group A beta-hemolytic streptococcal infections, are a major trigger in neonates and infants. Other exacerbating factors in children include emotional stress, secondhand cigarette smoke, Kawasaki disease, and withdrawal from systemic corticosteroids.

Psoriatic arthritis (PsA) is a burdensome comorbidity affecting children with psoriasis. The prevalence of joint disease is 15-times greater in children with psoriasis vs those without,³ and 80% of children with PsA develop rheumatologic symptoms, which typically include oligoarticular disease and dactylitis in infants and girls and enthesitis and axial joint involvement in boys and older children, years prior to the onset of cutaneous disease.⁴ Uveitis often occurs in children with psoriasis and PsA but not in those with isolated cutaneous disease.

Compared to unaffected children, pediatric patients with psoriasis have greater prevalence of metabolic and cardiovascular risk factors during childhood, including central obesity, hypertension, hypertriglyceridemia, hypercholesterolemia, insulin resistance, atherosclerosis, arrythmia, and valvular heart disease. Family history of obesity increases the risk for early-onset development of cutaneous lesions,^5,6 and weight reduction may alleviate severity of psoriasis lesions.⁷ In the United States, many of the metabolic associations observed are particularly robust in Black and Hispanic children vs those of other races. Furthermore, the prevalence of inflammatory bowel disease is 3- to 4-times higher in children with psoriasis compared to those without.

As with other cutaneous diseases, it is important to be aware of social and mental health concerns in children with psoriasis. The majority of pediatric patients with psoriasis experience name-calling, shaming, or bullying, and many have concerns from skin shedding and malodor. Independent risk for depression after the onset of psoriasis is high. Affected older children and adolescents are at increased risk for alcohol and drug abuse as well as eating disorders.

Despite these identified comorbidities, there are no unique screening recommendations for arthritis, ophthalmologic disease, metabolic disease, cardiovascular disease, gastrointestinal tract disease, or mental health issues in children with psoriasis. Rather, these patients should be monitored according to the American Academy of Pediatrics or American Diabetes Association guidelines for all pediatric patients.^8,9 Nonetheless, educating patients and guardians about these potential issues may be warranted.

Topical Therapies

For children with mild to moderate psoriasis, topical therapies are first line. Despite being off label, topical corticosteroids are the mainstay of therapy for localized psoriatic plaques in children. Topical vitamin D analogues—calcitriol and calcipotriol/calcipotriene—are highly effective and well tolerated, and they frequently are used in combination with topical corticosteroids. Topical calcineurin inhibitors, namely tacrolimus, also are used off label but are considered first line for sensitive regions of the skin in children, including the face, genitalia, and body folds. There currently is limited evidence for supporting the use of the topical vitamin A analogue tazarotene in children with psoriasis, though some consider its off-label use effective for pediatric nail psoriasis. It also may be used as an adjunct to topical corticosteroids to minimize irritation.

Although there is no gold standard topical regimen, combination therapy with a high-potency topical steroid and topical vitamin D analogue commonly is used to minimize steroid-induced side effects. For the first 2 weeks of treatment, they each may be applied once daily or mixed together and applied twice daily. For subsequent maintenance, topical calcipotriene may be applied on weekdays and topical steroids only on weekends. Combination calcipotriol–betamethasone dipropionate also is available as cream, ointment, foam, and suspension vehicles for use on the body and scalp in children aged 12 years and older. Tacrolimus ointment 0.1% may be applied in a thin layer up to twice daily. Concurrent emollient use also is recommended with these therapies.

Health care providers should educate patients and guardians about the potential side effects of topical therapies. They also should provide explicit instructions for amount, site, frequency, and duration of application. Topical corticosteroids commonly result in burning on application and may potentially cause skin thinning and striae with overuse. Topical vitamin D analogues may result in local irritation that may be improved by concurrent emollient use, and they generally should be avoided on sensitive sites. Topical calcineurin inhibitors are associated with burning, stinging, and pruritus, and the US Food and Drug Administration has issued a black-box warning related to risk for lymphoma with their chronic intermittent use. However, it was based on rare reports of lymphoma in transplant patients taking oral calcineurin inhibitors; no clinical trials to date in humans have demonstrated an increased risk for malignancy with topical calcineurin inhibitors.¹⁰ Tazarotene should be used cautiously in females of childbearing age given its teratogenic potential.

Children younger than 7 years are especially prone to suppression of the hypothalamic-pituitary-adrenal axis from topical corticosteroid therapy and theoretically hypercalcemia and hypervitaminosis D from topical vitamin D analogues, as their high BSA-to-volume ratio increases potential for systemic absorption. Children should avoid occlusive application of topical vitamin D analogues to large areas of the skin. Monitoring of vitamin D metabolites in the serum may be considered if calcipotriene or calcipotriol application to a large BSA is warranted.

Light-Based Therapy

In children with widespread psoriasis or those refractory to topical therapy, phototherapy may be considered. Narrowband UVB (311- to 313-nm wavelength) therapy is considered a first-line form of phototherapy in pediatric psoriasis. Mineral oil or emollient pretreatment to affected areas may augment the efficacy of UV-based treatments.¹¹ Excimer laser and UVA also may be efficacious, though evidence is limited in children. Treatment is recommended to start at 3 days a week, and once improvement is seen, the frequency can be decreased to 2 days a week. Once desired clearance is achieved, maintenance therapy can be continued at even longer intervals. Adjunctive use of tar preparations may potentiate the efficacy of phototherapy, though there is a theoretical increased risk for carcinogenicity with prolonged use of coal tar. Side effects of phototherapy include erythema, blistering hyperpigmentation, and pruritus. Psoralen is contraindicated in children younger than 12 years. All forms of phototherapy are contraindicated in children with generalized erythroderma and cutaneous cancer syndromes. Other important pediatric-specific considerations include anxiety that may be provoked by UV light machines and inconvenience of frequent appointments.

Nonbiologic Systemic Therapies

Systemic therapies may be considered in children with recalcitrant, widespread, or rapidly progressing psoriasis, particularly if the disease is accompanied by severe emotional and psychological burden. These drugs, which include methotrexate, cyclosporine, and acitretin (see eTable for recommended dosing), are advantageous in that they may be combined with other therapies; however, they have potential for dangerous toxicities.

Methotrexate is the most frequently utilized systemic therapy for psoriasis worldwide in children because of its low cost, once-weekly dosing, and the substantial amount of long-term efficacy and safety data available in the pediatric population. It is slow acting initially but has excellent long-term efficacy for nearly every subtype of psoriasis. The most common side effect of methotrexate is gastrointestinal tract intolerance. Nonetheless, adverse events are rare in children without prior history, with 1 large study (N=289) reporting no adverse events in more than 90% of patients aged 9 to 14 years treated with methotrexate.¹² Current guidelines recommend monitoring for bone marrow suppression and elevated transaminase levels 4 to 6 days after initiating treatment.¹ The absolute contraindications for methotrexate are pregnancy and liver disease, and caution should be taken in children with metabolic risk factors. Adolescents must be counseled regarding the elevated risk for hepatotoxicity associated with alcohol ingestion. Methotrexate therapy also requires 1 mg folic acid supplementation 6 to 7 days a week, which decreases the risk for developing folic acid deficiency and may decrease gastrointestinal tract intolerance and hepatic side effects that may result from therapy.

Cyclosporine is an effective and well-tolerated option for rapid control of severe psoriasis in children. It is useful for various types of psoriasis but generally is reserved for more severe subtypes, such as generalized pustular psoriasis, erythrodermic psoriasis, and uncontrolled plaque psoriasis. Long-term use of cyclosporine may result in renal toxicity and hypertension, and this therapy is absolutely contraindicated in children with kidney disease or hypertension at baseline. It is strongly recommended to evaluate blood pressure every week for the first month of therapy and at every subsequent follow-up visit, which may occur at variable intervals based on the judgement of the provider. Evaluation before and during treatment with cyclosporine also should include a complete blood cell count, complete metabolic panel, and lipid panel.

Systemic retinoids have a unique advantage over methotrexate and cyclosporine in that they are not immunosuppressive and therefore are not contraindicated in children who are very young or immunosuppressed. Children receiving systemic retinoids also can receive routine live vaccines—measles-mumps-rubella, varicella zoster, and rotavirus—that are contraindicated with other systemic therapies. Acitretin is particularly effective in pediatric patients with diffuse guttate psoriasis, pustular psoriasis, and palmoplantar psoriasis. Narrowband UVB therapy has been shown to augment the effectiveness of acitretin in children, which may allow for reduced acitretin dosing. Pustular psoriasis may respond as quickly as 3 weeks after initiation, whereas it may take 2 to 3 months before improvement is noticed in plaque psoriasis. Side effects of retinoids include skin dryness, hyperlipidemia, and gastrointestinal tract upset. The most severe long-term concern is skeletal toxicity, including premature epiphyseal closure, hyperostosis, periosteal bone formation, and decreased bone mineral density.¹ Vitamin A derivatives also are known teratogens and should be avoided in females of childbearing potential. Lipids and transaminases should be monitored routinely, and screening for depression and psychiatric symptoms should be performed frequently.¹

When utilizing systemic therapies, the objective should be to control the disease, maintain stability, and ultimately taper to the lowest effective dose or transition to a topical therapy, if feasible. Although no particular systemic therapy is recommended as first line for children with psoriasis, it is important to consider comorbidities, contraindications, monitoring frequency, mode of administration (injectable therapies elicit more psychological trauma in children than oral therapies), and expense when determining the best choice.

Biologics

Biologic agents are associated with very high to total psoriatic plaque clearance rates and require infrequent dosing and monitoring. However, their use may be limited by cost and injection phobias in children as well as limited evidence for their efficacy and safety in pediatric psoriasis. Several studies have established the safety and effectiveness of biologics in children with plaque psoriasis (see eTable for recommended dosing), whereas the evidence supporting their use in treating pustular and erythrodermic variants are limited to case reports and case series. The tumor necrosis factor α (TNF-α) inhibitor etanercept has been approved for use in children aged 4 years and older, and the IL-12/IL-23 inhibitor ustekinumab is approved in children aged 6 years and older. Other TNF-α inhibitors, namely infliximab and adalimumab, commonly are utilized off label for pediatric psoriasis. The most common side effect of biologic therapies in pediatric patients is injection-site reactions.¹ Prior to initiating therapy, children must undergo tuberculosis screening either by purified protein derivative testing or IFN-γ release assay. Testing should be repeated annually in individuals taking TNF-α inhibitors, though the utility of repeat testing when taking biologics in other classes is not clear. High-risk patients also should be screened for human immunodeficiency virus and hepatitis. Follow-up frequency may range from every 3 months to annually, based on judgement of the provider. In children who develop loss of response to biologics, methotrexate can be added to the regimen to attenuate formation of efficacy-reducing antidrug antibodies.

Final Thoughts

When managing children with psoriasis, it is important for dermatologists to appropriately educate guardians and children on the disease course, as well as consider the psychological, emotional, social, and financial factors that may direct decision-making regarding optimal therapeutics. Dermatologists should consider collaboration with the child’s primary care physician and other specialists to ensure that all needs are met.

These guidelines provide a framework agreed upon by numerous experts in pediatric psoriasis, but they are limited by gaps in the research. There still is much to be learned regarding the pathophysiology of psoriasis; the risk for developing comorbidities during adulthood; and the efficacy and safety of certain therapeutics, particularly biologics, in pediatric patients with psoriasis.

In November 2019, the American Academy of Dermatology (AAD) and the National Psoriasis Foundation (NPF) released their first set of recommendations for the management of pediatric psoriasis.¹ The pediatric guidelines discuss methods of quantifying disease severity in children, triggers and comorbidities, and the efficacy and safety of various therapeutic agents. This review aims to discuss, in a condensed form, special considerations unique to the management of children with psoriasis as presented in the guidelines as well as grade A– and grade B–level treatment recommendations (Table).

Quantifying Psoriasis Severity in Children

Percentage body surface area (BSA) involvement is the most common mode of grading psoriasis severity, with less than 3% BSA involvement being considered mild, 3% to 10% BSA moderate, and more than 10% severe disease. In children, the standard method of measuring BSA is the rule of 9’s: the head and each arm make up 9% of the total BSA, each leg and the front and back of the torso respectively each make up 18%, and the genitalia make up 1%. It also is important to consider impact on quality of life, which may be remarkable in spite of limited BSA involvement. The children’s dermatology life quality index score may be utilized in combination with affected BSA to determine the burden of psoriasis in context of impact on daily life. This metric is available in both written and cartoon form, and it consists of 10 questions that include variables such as severity of itch, impact on social life, and effects on sleep. Most notably, this tool incorporates pruritus,² which generally is addressed inadequately in pediatric psoriasis.

Triggers and Comorbidities in Pediatric Patients

In children, it is important to identify and eliminate modifiable factors that may prompt psoriasis flares. Infections, particularly group A beta-hemolytic streptococcal infections, are a major trigger in neonates and infants. Other exacerbating factors in children include emotional stress, secondhand cigarette smoke, Kawasaki disease, and withdrawal from systemic corticosteroids.

Psoriatic arthritis (PsA) is a burdensome comorbidity affecting children with psoriasis. The prevalence of joint disease is 15-times greater in children with psoriasis vs those without,³ and 80% of children with PsA develop rheumatologic symptoms, which typically include oligoarticular disease and dactylitis in infants and girls and enthesitis and axial joint involvement in boys and older children, years prior to the onset of cutaneous disease.⁴ Uveitis often occurs in children with psoriasis and PsA but not in those with isolated cutaneous disease.

Compared to unaffected children, pediatric patients with psoriasis have greater prevalence of metabolic and cardiovascular risk factors during childhood, including central obesity, hypertension, hypertriglyceridemia, hypercholesterolemia, insulin resistance, atherosclerosis, arrythmia, and valvular heart disease. Family history of obesity increases the risk for early-onset development of cutaneous lesions,^5,6 and weight reduction may alleviate severity of psoriasis lesions.⁷ In the United States, many of the metabolic associations observed are particularly robust in Black and Hispanic children vs those of other races. Furthermore, the prevalence of inflammatory bowel disease is 3- to 4-times higher in children with psoriasis compared to those without.

As with other cutaneous diseases, it is important to be aware of social and mental health concerns in children with psoriasis. The majority of pediatric patients with psoriasis experience name-calling, shaming, or bullying, and many have concerns from skin shedding and malodor. Independent risk for depression after the onset of psoriasis is high. Affected older children and adolescents are at increased risk for alcohol and drug abuse as well as eating disorders.

Despite these identified comorbidities, there are no unique screening recommendations for arthritis, ophthalmologic disease, metabolic disease, cardiovascular disease, gastrointestinal tract disease, or mental health issues in children with psoriasis. Rather, these patients should be monitored according to the American Academy of Pediatrics or American Diabetes Association guidelines for all pediatric patients.^8,9 Nonetheless, educating patients and guardians about these potential issues may be warranted.

Topical Therapies

For children with mild to moderate psoriasis, topical therapies are first line. Despite being off label, topical corticosteroids are the mainstay of therapy for localized psoriatic plaques in children. Topical vitamin D analogues—calcitriol and calcipotriol/calcipotriene—are highly effective and well tolerated, and they frequently are used in combination with topical corticosteroids. Topical calcineurin inhibitors, namely tacrolimus, also are used off label but are considered first line for sensitive regions of the skin in children, including the face, genitalia, and body folds. There currently is limited evidence for supporting the use of the topical vitamin A analogue tazarotene in children with psoriasis, though some consider its off-label use effective for pediatric nail psoriasis. It also may be used as an adjunct to topical corticosteroids to minimize irritation.

Although there is no gold standard topical regimen, combination therapy with a high-potency topical steroid and topical vitamin D analogue commonly is used to minimize steroid-induced side effects. For the first 2 weeks of treatment, they each may be applied once daily or mixed together and applied twice daily. For subsequent maintenance, topical calcipotriene may be applied on weekdays and topical steroids only on weekends. Combination calcipotriol–betamethasone dipropionate also is available as cream, ointment, foam, and suspension vehicles for use on the body and scalp in children aged 12 years and older. Tacrolimus ointment 0.1% may be applied in a thin layer up to twice daily. Concurrent emollient use also is recommended with these therapies.

Health care providers should educate patients and guardians about the potential side effects of topical therapies. They also should provide explicit instructions for amount, site, frequency, and duration of application. Topical corticosteroids commonly result in burning on application and may potentially cause skin thinning and striae with overuse. Topical vitamin D analogues may result in local irritation that may be improved by concurrent emollient use, and they generally should be avoided on sensitive sites. Topical calcineurin inhibitors are associated with burning, stinging, and pruritus, and the US Food and Drug Administration has issued a black-box warning related to risk for lymphoma with their chronic intermittent use. However, it was based on rare reports of lymphoma in transplant patients taking oral calcineurin inhibitors; no clinical trials to date in humans have demonstrated an increased risk for malignancy with topical calcineurin inhibitors.¹⁰ Tazarotene should be used cautiously in females of childbearing age given its teratogenic potential.

Children younger than 7 years are especially prone to suppression of the hypothalamic-pituitary-adrenal axis from topical corticosteroid therapy and theoretically hypercalcemia and hypervitaminosis D from topical vitamin D analogues, as their high BSA-to-volume ratio increases potential for systemic absorption. Children should avoid occlusive application of topical vitamin D analogues to large areas of the skin. Monitoring of vitamin D metabolites in the serum may be considered if calcipotriene or calcipotriol application to a large BSA is warranted.

Light-Based Therapy

In children with widespread psoriasis or those refractory to topical therapy, phototherapy may be considered. Narrowband UVB (311- to 313-nm wavelength) therapy is considered a first-line form of phototherapy in pediatric psoriasis. Mineral oil or emollient pretreatment to affected areas may augment the efficacy of UV-based treatments.¹¹ Excimer laser and UVA also may be efficacious, though evidence is limited in children. Treatment is recommended to start at 3 days a week, and once improvement is seen, the frequency can be decreased to 2 days a week. Once desired clearance is achieved, maintenance therapy can be continued at even longer intervals. Adjunctive use of tar preparations may potentiate the efficacy of phototherapy, though there is a theoretical increased risk for carcinogenicity with prolonged use of coal tar. Side effects of phototherapy include erythema, blistering hyperpigmentation, and pruritus. Psoralen is contraindicated in children younger than 12 years. All forms of phototherapy are contraindicated in children with generalized erythroderma and cutaneous cancer syndromes. Other important pediatric-specific considerations include anxiety that may be provoked by UV light machines and inconvenience of frequent appointments.

Nonbiologic Systemic Therapies

Systemic therapies may be considered in children with recalcitrant, widespread, or rapidly progressing psoriasis, particularly if the disease is accompanied by severe emotional and psychological burden. These drugs, which include methotrexate, cyclosporine, and acitretin (see eTable for recommended dosing), are advantageous in that they may be combined with other therapies; however, they have potential for dangerous toxicities.

Methotrexate is the most frequently utilized systemic therapy for psoriasis worldwide in children because of its low cost, once-weekly dosing, and the substantial amount of long-term efficacy and safety data available in the pediatric population. It is slow acting initially but has excellent long-term efficacy for nearly every subtype of psoriasis. The most common side effect of methotrexate is gastrointestinal tract intolerance. Nonetheless, adverse events are rare in children without prior history, with 1 large study (N=289) reporting no adverse events in more than 90% of patients aged 9 to 14 years treated with methotrexate.¹² Current guidelines recommend monitoring for bone marrow suppression and elevated transaminase levels 4 to 6 days after initiating treatment.¹ The absolute contraindications for methotrexate are pregnancy and liver disease, and caution should be taken in children with metabolic risk factors. Adolescents must be counseled regarding the elevated risk for hepatotoxicity associated with alcohol ingestion. Methotrexate therapy also requires 1 mg folic acid supplementation 6 to 7 days a week, which decreases the risk for developing folic acid deficiency and may decrease gastrointestinal tract intolerance and hepatic side effects that may result from therapy.

Cyclosporine is an effective and well-tolerated option for rapid control of severe psoriasis in children. It is useful for various types of psoriasis but generally is reserved for more severe subtypes, such as generalized pustular psoriasis, erythrodermic psoriasis, and uncontrolled plaque psoriasis. Long-term use of cyclosporine may result in renal toxicity and hypertension, and this therapy is absolutely contraindicated in children with kidney disease or hypertension at baseline. It is strongly recommended to evaluate blood pressure every week for the first month of therapy and at every subsequent follow-up visit, which may occur at variable intervals based on the judgement of the provider. Evaluation before and during treatment with cyclosporine also should include a complete blood cell count, complete metabolic panel, and lipid panel.

Systemic retinoids have a unique advantage over methotrexate and cyclosporine in that they are not immunosuppressive and therefore are not contraindicated in children who are very young or immunosuppressed. Children receiving systemic retinoids also can receive routine live vaccines—measles-mumps-rubella, varicella zoster, and rotavirus—that are contraindicated with other systemic therapies. Acitretin is particularly effective in pediatric patients with diffuse guttate psoriasis, pustular psoriasis, and palmoplantar psoriasis. Narrowband UVB therapy has been shown to augment the effectiveness of acitretin in children, which may allow for reduced acitretin dosing. Pustular psoriasis may respond as quickly as 3 weeks after initiation, whereas it may take 2 to 3 months before improvement is noticed in plaque psoriasis. Side effects of retinoids include skin dryness, hyperlipidemia, and gastrointestinal tract upset. The most severe long-term concern is skeletal toxicity, including premature epiphyseal closure, hyperostosis, periosteal bone formation, and decreased bone mineral density.¹ Vitamin A derivatives also are known teratogens and should be avoided in females of childbearing potential. Lipids and transaminases should be monitored routinely, and screening for depression and psychiatric symptoms should be performed frequently.¹

When utilizing systemic therapies, the objective should be to control the disease, maintain stability, and ultimately taper to the lowest effective dose or transition to a topical therapy, if feasible. Although no particular systemic therapy is recommended as first line for children with psoriasis, it is important to consider comorbidities, contraindications, monitoring frequency, mode of administration (injectable therapies elicit more psychological trauma in children than oral therapies), and expense when determining the best choice.

Biologics

Biologic agents are associated with very high to total psoriatic plaque clearance rates and require infrequent dosing and monitoring. However, their use may be limited by cost and injection phobias in children as well as limited evidence for their efficacy and safety in pediatric psoriasis. Several studies have established the safety and effectiveness of biologics in children with plaque psoriasis (see eTable for recommended dosing), whereas the evidence supporting their use in treating pustular and erythrodermic variants are limited to case reports and case series. The tumor necrosis factor α (TNF-α) inhibitor etanercept has been approved for use in children aged 4 years and older, and the IL-12/IL-23 inhibitor ustekinumab is approved in children aged 6 years and older. Other TNF-α inhibitors, namely infliximab and adalimumab, commonly are utilized off label for pediatric psoriasis. The most common side effect of biologic therapies in pediatric patients is injection-site reactions.¹ Prior to initiating therapy, children must undergo tuberculosis screening either by purified protein derivative testing or IFN-γ release assay. Testing should be repeated annually in individuals taking TNF-α inhibitors, though the utility of repeat testing when taking biologics in other classes is not clear. High-risk patients also should be screened for human immunodeficiency virus and hepatitis. Follow-up frequency may range from every 3 months to annually, based on judgement of the provider. In children who develop loss of response to biologics, methotrexate can be added to the regimen to attenuate formation of efficacy-reducing antidrug antibodies.

Final Thoughts

When managing children with psoriasis, it is important for dermatologists to appropriately educate guardians and children on the disease course, as well as consider the psychological, emotional, social, and financial factors that may direct decision-making regarding optimal therapeutics. Dermatologists should consider collaboration with the child’s primary care physician and other specialists to ensure that all needs are met.

These guidelines provide a framework agreed upon by numerous experts in pediatric psoriasis, but they are limited by gaps in the research. There still is much to be learned regarding the pathophysiology of psoriasis; the risk for developing comorbidities during adulthood; and the efficacy and safety of certain therapeutics, particularly biologics, in pediatric patients with psoriasis.

Psoriasis and atopic dermatitis (AD) can impact quality of life (QOL) in pediatric patients, warranting early recognition and treatment.¹ Topical agents often are inadequate to treat moderate to severe disease, but the potential toxicity of systemic agents, which largely include immunosuppressives, limit their use in this population despite their effectiveness. Our expanding knowledge of the pathogenesis of psoriasis (tumor necrosis factor [TNF] α and IL-23/T_H17 pathways) and AD has led to targeted interventions, particularly monoclonal antibody biologics, which have revolutionized treatment for affected adults and more recently children. Several agents are approved by the US Food and Drug Administration (FDA) for pediatric psoriasis, and dupilumab is approved for pediatric AD. Herein, we discuss the latest developments in the treatment landscape for pediatric psoriasis and AD.

Pediatric Psoriasis

Methotrexate (MTX) and cyclosporine have been FDA approved for psoriasis in adults since 1972 and 1997, respectively.² Before biologics, MTX was the primary systemic agent used to treat pediatric psoriasis, given its lower toxicity vs cyclosporine. The TNF-α inhibitor etanercept became the first FDA-approved biologic for pediatric psoriasis in 2016. Adalimumab has been available in Europe for children since 2015 but is not FDA approved. Certolizumab, a pegylated TNF-α inhibitor that distinctly fails to cross the placental barrier currently is in clinical trials (ClinicalTrials.gov identifier NCT04123795). Tumor necrosis factor α inhibitors have shown more rapid onset and greater efficacy during the first 16 weeks of use than MTX, including a head-to-head trial comparing MTX to adalimumab.³ A recent real-world study showed that pediatric patients receiving biologics, primarily TNF-α inhibitors, were more likely to achieve psoriasis area and severity index (PASI) 75 or clear/almost clear status (similar to PASI 90) than MTX and had higher drug survival rates.⁴

Ustekinumab targets both IL-12 and IL-23, which share the IL-23 receptor p40 subunit. It was the first biologic to target IL-23, which promotes the proliferation and survival of helper T cells (T_H17). Ustekinumab has led to greater reductions in PASI scores than TNF-α inhibitors.^5,6 Pediatric trials of guselkumab, risankizumab, and tildrakizumab, all targeting the IL-23 receptor–specific p19 subunit, are completed or currently recruiting (NCT03451851, NCT03997786, NCT04435600). Ixekizumab is the first IL-17A–targeting biologic approved for children.⁷ Secukinumab and the IL-17 receptor inhibitor brodalumab are in pediatric trials (NCT03668613, NCT04305327, NCT03240809). One potential issue with T_H17 pathway inhibitors is their association with inflammatory bowel disease, a contraindication when considering if a patient is a potential candidate for treatment.

Skin disease can profoundly affect QOL during childhood and adolescence, a critical time for psychosocial development. In psoriasis, improvement in QOL is proportional to clearance and is greater when PASI 90 is achieved vs PASI 75.⁸ The high efficacy of IL-23 and IL-17A pathway inhibitors now makes achieving at least PASI 90 the new standard, which can be reached in most patients.

Pediatric AD

For AD in the pediatric population, systemic treatments primarily include corticosteroids, mycophenolate mofetil, azathioprine, cyclosporine, and MTX. Although cyclosporine was the favored systemic agent among pediatric dermatologists in one study,⁹ claims data analyses show that systemic corticosteroids are used much more often overall, prescribed in 24.4% (116,635 total cases) of children with AD vs nonsteroidal immunosuppressants in less than 0.5%.¹⁰ Systemic steroids are impractical given their side effects and risk for disease rebound; however, no immunosuppressants are safe for long-term use, and all require frequent laboratory monitoring. The development of biologics for AD largely involves targeting T_H2-driven inflammation.¹¹ Dupilumab is the only FDA-approved biologic for moderate to severe pediatric AD, including in patients as young as 6 years of age. Dupilumab inhibits activation of the IL-4Rα subunit, thereby blocking responses to its ligands, IL-4 and IL-13. Phase 3 trials are now underway in children aged 6 months to 5 years (NCT02612454, NCT03346434). The concomitant ameliorative effects of dupilumab on asthma and other allergic disorders, occurring in approximately 90% of children with moderate to severe AD, is an added benefit.¹² Although dupilumab does not appear to modify the disease course in children with AD, the possibility that early introduction could reduce the risk for later developing allergic disease is intriguing.

Adolescent trials have been started for lebrikizumab (NCT04392154) and have been completed for tralokinumab (NCT03160885). Both agents selectively target IL-13 to block T_H2 pathway inflammation. The only reported adverse effects of IL-4Rα and IL-13 inhibitors have been injection-site pain/reactions and increased conjunctivitis.¹³

The only other biologic for AD currently in clinical trials for adolescents is nemolizumab, targeting the receptor for IL-31, a predominantly T_H2 cytokine that causes pruritus (NCT03989349). In adults, nemolizumab has shown rapid and potent suppression of itch (but not inflammation) without adding topical corticosteroids.¹⁴

Advantages of Biologics and Laboratory Monitoring

By targeting specific cytokines, biologics have greater and more rapid efficacy, fewer side effects, fewer drug interactions, less frequent dosing, and less immunosuppression compared to other systemic agents.^3,4,15,16

Recent pediatric-specific guidelines for psoriasis recommend baseline monitoring for tuberculosis for all biologics but yearly tuberculosis testing only for TNF-α inhibitors unless the individual patient is at increased risk.² No tuberculosis testing is needed for dupilumab, and no other laboratory monitoring is recommended for any biologic in children unless warranted by risk. This difference in recommended monitoring suggests the safety of biologics and is advantageous in managing pediatric therapy.

Unanswered Questions: Vaccines and Antidrug Antibodies

Although administration of killed vaccines is considered safe with all approved biologics, questions remain about the safety of administering live vaccines while on biologics, a particularly pertinent issue in younger children treated with dupilumab and other biologics for AD. Another unanswered question is the potential reduction in clinical response and drug durability with intermittent use of biologics due to the potential development of neutralizing antidrug antibodies (ADAs). The ability to discontinue medication intermittently is desirable, both to determine the natural course of the underlying disease and give a holiday as tolerated. Newer biologics are thought to have lower immunogenicity and less frequent ADA development.^17-19 Even with TNF-α inhibitors, the presence of anti-ADAs is not temporally related to response in children with psoriasis.²⁰ Long-term outcomes of the use of biologics in adults have been reassuring, and safety profiles of biologics studied thus far appear to be similar in children.^21,22 However, understanding the potential long-term effects from the use of newly approved and emerging biologics in the pediatric population will require decades of study to ensure safety, including nonrandomized studies and postmarketing reports from regulatory agencies.

Cost Considerations

Biologics are disease and QOL altering for children with moderate to severe psoriasis or AD; however, access to biologics often is an obstacle for patients and practitioners. Biologics cost $30,000 to $60,000 annually, while conventional systemic treatments such as MTX, cyclosporine, and acitretin cost $100 to $3000 annually, raising the question of cost effectiveness. In 2016, the Institute for Clinical and Economic Review concluded that biologics for psoriasis had reasonably good value based on improved QOL and concluded in 2017 that dupilumab had a benefit that outweighed its cost.^23,24 Prior authorizations and multiple appeals have been necessary to obtain approval, especially in the pediatric population.²⁵ This difficulty highlights the need for programs to cover the cost of biologics for all children, as well as registries to further assess effectiveness and long-term safety, especially compared to traditional systemic agents.

On the Horizon

Clinical trials for other therapies for children and adolescents are ongoing. Details on recommended dosing, approval status, and efficacy in trials are provided in the eTable. Given their high efficacy in adults with psoriasis, IL-23–specific and T_H17 pathway biologics likely are similarly efficacious and raise the bar for the expectation of achieving PASI 90 and PASI 100 responses. The long-term safety, durability of responses, and ability to modify disease, particularly when started early in life (eg, preadolescence) and early in the disease course, remains to be determined.

Psoriasis and atopic dermatitis (AD) can impact quality of life (QOL) in pediatric patients, warranting early recognition and treatment.¹ Topical agents often are inadequate to treat moderate to severe disease, but the potential toxicity of systemic agents, which largely include immunosuppressives, limit their use in this population despite their effectiveness. Our expanding knowledge of the pathogenesis of psoriasis (tumor necrosis factor [TNF] α and IL-23/T_H17 pathways) and AD has led to targeted interventions, particularly monoclonal antibody biologics, which have revolutionized treatment for affected adults and more recently children. Several agents are approved by the US Food and Drug Administration (FDA) for pediatric psoriasis, and dupilumab is approved for pediatric AD. Herein, we discuss the latest developments in the treatment landscape for pediatric psoriasis and AD.

Pediatric Psoriasis

Methotrexate (MTX) and cyclosporine have been FDA approved for psoriasis in adults since 1972 and 1997, respectively.² Before biologics, MTX was the primary systemic agent used to treat pediatric psoriasis, given its lower toxicity vs cyclosporine. The TNF-α inhibitor etanercept became the first FDA-approved biologic for pediatric psoriasis in 2016. Adalimumab has been available in Europe for children since 2015 but is not FDA approved. Certolizumab, a pegylated TNF-α inhibitor that distinctly fails to cross the placental barrier currently is in clinical trials (ClinicalTrials.gov identifier NCT04123795). Tumor necrosis factor α inhibitors have shown more rapid onset and greater efficacy during the first 16 weeks of use than MTX, including a head-to-head trial comparing MTX to adalimumab.³ A recent real-world study showed that pediatric patients receiving biologics, primarily TNF-α inhibitors, were more likely to achieve psoriasis area and severity index (PASI) 75 or clear/almost clear status (similar to PASI 90) than MTX and had higher drug survival rates.⁴

Ustekinumab targets both IL-12 and IL-23, which share the IL-23 receptor p40 subunit. It was the first biologic to target IL-23, which promotes the proliferation and survival of helper T cells (T_H17). Ustekinumab has led to greater reductions in PASI scores than TNF-α inhibitors.^5,6 Pediatric trials of guselkumab, risankizumab, and tildrakizumab, all targeting the IL-23 receptor–specific p19 subunit, are completed or currently recruiting (NCT03451851, NCT03997786, NCT04435600). Ixekizumab is the first IL-17A–targeting biologic approved for children.⁷ Secukinumab and the IL-17 receptor inhibitor brodalumab are in pediatric trials (NCT03668613, NCT04305327, NCT03240809). One potential issue with T_H17 pathway inhibitors is their association with inflammatory bowel disease, a contraindication when considering if a patient is a potential candidate for treatment.

Skin disease can profoundly affect QOL during childhood and adolescence, a critical time for psychosocial development. In psoriasis, improvement in QOL is proportional to clearance and is greater when PASI 90 is achieved vs PASI 75.⁸ The high efficacy of IL-23 and IL-17A pathway inhibitors now makes achieving at least PASI 90 the new standard, which can be reached in most patients.

Pediatric AD

For AD in the pediatric population, systemic treatments primarily include corticosteroids, mycophenolate mofetil, azathioprine, cyclosporine, and MTX. Although cyclosporine was the favored systemic agent among pediatric dermatologists in one study,⁹ claims data analyses show that systemic corticosteroids are used much more often overall, prescribed in 24.4% (116,635 total cases) of children with AD vs nonsteroidal immunosuppressants in less than 0.5%.¹⁰ Systemic steroids are impractical given their side effects and risk for disease rebound; however, no immunosuppressants are safe for long-term use, and all require frequent laboratory monitoring. The development of biologics for AD largely involves targeting T_H2-driven inflammation.¹¹ Dupilumab is the only FDA-approved biologic for moderate to severe pediatric AD, including in patients as young as 6 years of age. Dupilumab inhibits activation of the IL-4Rα subunit, thereby blocking responses to its ligands, IL-4 and IL-13. Phase 3 trials are now underway in children aged 6 months to 5 years (NCT02612454, NCT03346434). The concomitant ameliorative effects of dupilumab on asthma and other allergic disorders, occurring in approximately 90% of children with moderate to severe AD, is an added benefit.¹² Although dupilumab does not appear to modify the disease course in children with AD, the possibility that early introduction could reduce the risk for later developing allergic disease is intriguing.

Adolescent trials have been started for lebrikizumab (NCT04392154) and have been completed for tralokinumab (NCT03160885). Both agents selectively target IL-13 to block T_H2 pathway inflammation. The only reported adverse effects of IL-4Rα and IL-13 inhibitors have been injection-site pain/reactions and increased conjunctivitis.¹³

The only other biologic for AD currently in clinical trials for adolescents is nemolizumab, targeting the receptor for IL-31, a predominantly T_H2 cytokine that causes pruritus (NCT03989349). In adults, nemolizumab has shown rapid and potent suppression of itch (but not inflammation) without adding topical corticosteroids.¹⁴

Advantages of Biologics and Laboratory Monitoring

By targeting specific cytokines, biologics have greater and more rapid efficacy, fewer side effects, fewer drug interactions, less frequent dosing, and less immunosuppression compared to other systemic agents.^3,4,15,16

Recent pediatric-specific guidelines for psoriasis recommend baseline monitoring for tuberculosis for all biologics but yearly tuberculosis testing only for TNF-α inhibitors unless the individual patient is at increased risk.² No tuberculosis testing is needed for dupilumab, and no other laboratory monitoring is recommended for any biologic in children unless warranted by risk. This difference in recommended monitoring suggests the safety of biologics and is advantageous in managing pediatric therapy.

Unanswered Questions: Vaccines and Antidrug Antibodies

Although administration of killed vaccines is considered safe with all approved biologics, questions remain about the safety of administering live vaccines while on biologics, a particularly pertinent issue in younger children treated with dupilumab and other biologics for AD. Another unanswered question is the potential reduction in clinical response and drug durability with intermittent use of biologics due to the potential development of neutralizing antidrug antibodies (ADAs). The ability to discontinue medication intermittently is desirable, both to determine the natural course of the underlying disease and give a holiday as tolerated. Newer biologics are thought to have lower immunogenicity and less frequent ADA development.^17-19 Even with TNF-α inhibitors, the presence of anti-ADAs is not temporally related to response in children with psoriasis.²⁰ Long-term outcomes of the use of biologics in adults have been reassuring, and safety profiles of biologics studied thus far appear to be similar in children.^21,22 However, understanding the potential long-term effects from the use of newly approved and emerging biologics in the pediatric population will require decades of study to ensure safety, including nonrandomized studies and postmarketing reports from regulatory agencies.

Cost Considerations

Biologics are disease and QOL altering for children with moderate to severe psoriasis or AD; however, access to biologics often is an obstacle for patients and practitioners. Biologics cost $30,000 to $60,000 annually, while conventional systemic treatments such as MTX, cyclosporine, and acitretin cost $100 to $3000 annually, raising the question of cost effectiveness. In 2016, the Institute for Clinical and Economic Review concluded that biologics for psoriasis had reasonably good value based on improved QOL and concluded in 2017 that dupilumab had a benefit that outweighed its cost.^23,24 Prior authorizations and multiple appeals have been necessary to obtain approval, especially in the pediatric population.²⁵ This difficulty highlights the need for programs to cover the cost of biologics for all children, as well as registries to further assess effectiveness and long-term safety, especially compared to traditional systemic agents.

On the Horizon

Clinical trials for other therapies for children and adolescents are ongoing. Details on recommended dosing, approval status, and efficacy in trials are provided in the eTable. Given their high efficacy in adults with psoriasis, IL-23–specific and T_H17 pathway biologics likely are similarly efficacious and raise the bar for the expectation of achieving PASI 90 and PASI 100 responses. The long-term safety, durability of responses, and ability to modify disease, particularly when started early in life (eg, preadolescence) and early in the disease course, remains to be determined.

Psoriasis and atopic dermatitis (AD) can impact quality of life (QOL) in pediatric patients, warranting early recognition and treatment.¹ Topical agents often are inadequate to treat moderate to severe disease, but the potential toxicity of systemic agents, which largely include immunosuppressives, limit their use in this population despite their effectiveness. Our expanding knowledge of the pathogenesis of psoriasis (tumor necrosis factor [TNF] α and IL-23/T_H17 pathways) and AD has led to targeted interventions, particularly monoclonal antibody biologics, which have revolutionized treatment for affected adults and more recently children. Several agents are approved by the US Food and Drug Administration (FDA) for pediatric psoriasis, and dupilumab is approved for pediatric AD. Herein, we discuss the latest developments in the treatment landscape for pediatric psoriasis and AD.

Pediatric Psoriasis

Methotrexate (MTX) and cyclosporine have been FDA approved for psoriasis in adults since 1972 and 1997, respectively.² Before biologics, MTX was the primary systemic agent used to treat pediatric psoriasis, given its lower toxicity vs cyclosporine. The TNF-α inhibitor etanercept became the first FDA-approved biologic for pediatric psoriasis in 2016. Adalimumab has been available in Europe for children since 2015 but is not FDA approved. Certolizumab, a pegylated TNF-α inhibitor that distinctly fails to cross the placental barrier currently is in clinical trials (ClinicalTrials.gov identifier NCT04123795). Tumor necrosis factor α inhibitors have shown more rapid onset and greater efficacy during the first 16 weeks of use than MTX, including a head-to-head trial comparing MTX to adalimumab.³ A recent real-world study showed that pediatric patients receiving biologics, primarily TNF-α inhibitors, were more likely to achieve psoriasis area and severity index (PASI) 75 or clear/almost clear status (similar to PASI 90) than MTX and had higher drug survival rates.⁴

Ustekinumab targets both IL-12 and IL-23, which share the IL-23 receptor p40 subunit. It was the first biologic to target IL-23, which promotes the proliferation and survival of helper T cells (T_H17). Ustekinumab has led to greater reductions in PASI scores than TNF-α inhibitors.^5,6 Pediatric trials of guselkumab, risankizumab, and tildrakizumab, all targeting the IL-23 receptor–specific p19 subunit, are completed or currently recruiting (NCT03451851, NCT03997786, NCT04435600). Ixekizumab is the first IL-17A–targeting biologic approved for children.⁷ Secukinumab and the IL-17 receptor inhibitor brodalumab are in pediatric trials (NCT03668613, NCT04305327, NCT03240809). One potential issue with T_H17 pathway inhibitors is their association with inflammatory bowel disease, a contraindication when considering if a patient is a potential candidate for treatment.

Skin disease can profoundly affect QOL during childhood and adolescence, a critical time for psychosocial development. In psoriasis, improvement in QOL is proportional to clearance and is greater when PASI 90 is achieved vs PASI 75.⁸ The high efficacy of IL-23 and IL-17A pathway inhibitors now makes achieving at least PASI 90 the new standard, which can be reached in most patients.

Pediatric AD

For AD in the pediatric population, systemic treatments primarily include corticosteroids, mycophenolate mofetil, azathioprine, cyclosporine, and MTX. Although cyclosporine was the favored systemic agent among pediatric dermatologists in one study,⁹ claims data analyses show that systemic corticosteroids are used much more often overall, prescribed in 24.4% (116,635 total cases) of children with AD vs nonsteroidal immunosuppressants in less than 0.5%.¹⁰ Systemic steroids are impractical given their side effects and risk for disease rebound; however, no immunosuppressants are safe for long-term use, and all require frequent laboratory monitoring. The development of biologics for AD largely involves targeting T_H2-driven inflammation.¹¹ Dupilumab is the only FDA-approved biologic for moderate to severe pediatric AD, including in patients as young as 6 years of age. Dupilumab inhibits activation of the IL-4Rα subunit, thereby blocking responses to its ligands, IL-4 and IL-13. Phase 3 trials are now underway in children aged 6 months to 5 years (NCT02612454, NCT03346434). The concomitant ameliorative effects of dupilumab on asthma and other allergic disorders, occurring in approximately 90% of children with moderate to severe AD, is an added benefit.¹² Although dupilumab does not appear to modify the disease course in children with AD, the possibility that early introduction could reduce the risk for later developing allergic disease is intriguing.

Adolescent trials have been started for lebrikizumab (NCT04392154) and have been completed for tralokinumab (NCT03160885). Both agents selectively target IL-13 to block T_H2 pathway inflammation. The only reported adverse effects of IL-4Rα and IL-13 inhibitors have been injection-site pain/reactions and increased conjunctivitis.¹³

The only other biologic for AD currently in clinical trials for adolescents is nemolizumab, targeting the receptor for IL-31, a predominantly T_H2 cytokine that causes pruritus (NCT03989349). In adults, nemolizumab has shown rapid and potent suppression of itch (but not inflammation) without adding topical corticosteroids.¹⁴

Advantages of Biologics and Laboratory Monitoring

By targeting specific cytokines, biologics have greater and more rapid efficacy, fewer side effects, fewer drug interactions, less frequent dosing, and less immunosuppression compared to other systemic agents.^3,4,15,16

Recent pediatric-specific guidelines for psoriasis recommend baseline monitoring for tuberculosis for all biologics but yearly tuberculosis testing only for TNF-α inhibitors unless the individual patient is at increased risk.² No tuberculosis testing is needed for dupilumab, and no other laboratory monitoring is recommended for any biologic in children unless warranted by risk. This difference in recommended monitoring suggests the safety of biologics and is advantageous in managing pediatric therapy.

Unanswered Questions: Vaccines and Antidrug Antibodies

Although administration of killed vaccines is considered safe with all approved biologics, questions remain about the safety of administering live vaccines while on biologics, a particularly pertinent issue in younger children treated with dupilumab and other biologics for AD. Another unanswered question is the potential reduction in clinical response and drug durability with intermittent use of biologics due to the potential development of neutralizing antidrug antibodies (ADAs). The ability to discontinue medication intermittently is desirable, both to determine the natural course of the underlying disease and give a holiday as tolerated. Newer biologics are thought to have lower immunogenicity and less frequent ADA development.^17-19 Even with TNF-α inhibitors, the presence of anti-ADAs is not temporally related to response in children with psoriasis.²⁰ Long-term outcomes of the use of biologics in adults have been reassuring, and safety profiles of biologics studied thus far appear to be similar in children.^21,22 However, understanding the potential long-term effects from the use of newly approved and emerging biologics in the pediatric population will require decades of study to ensure safety, including nonrandomized studies and postmarketing reports from regulatory agencies.

Cost Considerations

Biologics are disease and QOL altering for children with moderate to severe psoriasis or AD; however, access to biologics often is an obstacle for patients and practitioners. Biologics cost $30,000 to $60,000 annually, while conventional systemic treatments such as MTX, cyclosporine, and acitretin cost $100 to $3000 annually, raising the question of cost effectiveness. In 2016, the Institute for Clinical and Economic Review concluded that biologics for psoriasis had reasonably good value based on improved QOL and concluded in 2017 that dupilumab had a benefit that outweighed its cost.^23,24 Prior authorizations and multiple appeals have been necessary to obtain approval, especially in the pediatric population.²⁵ This difficulty highlights the need for programs to cover the cost of biologics for all children, as well as registries to further assess effectiveness and long-term safety, especially compared to traditional systemic agents.

On the Horizon

Clinical trials for other therapies for children and adolescents are ongoing. Details on recommended dosing, approval status, and efficacy in trials are provided in the eTable. Given their high efficacy in adults with psoriasis, IL-23–specific and T_H17 pathway biologics likely are similarly efficacious and raise the bar for the expectation of achieving PASI 90 and PASI 100 responses. The long-term safety, durability of responses, and ability to modify disease, particularly when started early in life (eg, preadolescence) and early in the disease course, remains to be determined.

Biologic therapy for psoriasis may protect against severe COVID-19, according to two large observational studies from Italy and France presented at the virtual annual congress of the European Academy of Dermatology and Venereology.

“Biologics seem to be very protective against severe, poor-prognosis COVID-19, but they do not prevent infection with the virus,” reported Giovanni Damiani, MD, a dermatologist at the University of Milan.

This apparent protective effect of biologic agents against severe and even fatal COVID-19 is all the more impressive because the psoriasis patients included in the Italian study – as is true of those elsewhere throughout the world – had relatively high rates of obesity, smoking, and chronic obstructive pulmonary disease, known risk factors for severe COVID-19, he added.

He presented a case-control study including 1,193 adult psoriasis patients on biologics or apremilast (Otezla) at Milan’s San Donato Hospital during the period from Feb. 21 to April 9, 2020. The control group comprised more than 10 million individuals, the entire adult population of the Lombardy region, of which Milan is the capital. This was the hardest-hit area in all of Italy during the first wave of COVID-19.

Twenty-two of the 1,193 psoriasis patients experienced confirmed COVID-19 during the study period. Seventeen were quarantined at home because their disease was mild. Five were hospitalized. But no psoriasis patients were placed in intensive care, and none died.

Psoriasis patients on biologics were significantly more likely than the general Lombardian population to test positive for COVID-19, with an unadjusted odds ratio of 3.43. They were at 9.05-fold increased risk of home quarantine for mild disease, and at 3.59-fold greater risk than controls for hospitalization for COVID-19. However, they were not at significantly increased risk of ICU admission. And while they actually had a 59% relative risk reduction for death, this didn’t achieve statistical significance.

Forty-five percent of the psoriasis patients were on an interleukin-17 (IL-17) inhibitor, 22% were on a tumor necrosis factor–alpha inhibitor, and 20% were taking an IL-12/23 inhibitor. Of note, none of 77 patients on apremilast developed COVID-19, even though it is widely considered a less potent psoriasis therapy than the injectable monoclonal antibody biologics.

The French experience

Anne-Claire Fougerousse, MD, and her French coinvestigators conducted a study designed to address a different question: Is it safe to start psoriasis patients on biologics or older conventional systemic agents such as methotrexate during the pandemic?

She presented a French national cross-sectional study of 1,418 adult psoriasis patients on a biologic or standard systemic therapy during a snapshot in time near the peak of the first wave of the pandemic in France: the period from April 27 to May 7, 2020. The group included 1,188 psoriasis patients on maintenance therapy and 230 who had initiated systemic treatment within the past 4 months. More than one-third of the patients had at least one risk factor for severe COVID-19.

Although testing wasn’t available to confirm all cases, 54 patients developed probable COVID-19 during the study period. Only five required hospitalization. None died. The two hospitalized psoriasis patients admitted to an ICU had obesity as a risk factor for severe COVID-19, as did another of the five hospitalized patients, reported Dr. Fougerousse, a dermatologist at the Bégin Military Teaching Hospital in Saint-Mandé, France. Hospitalization for COVID-19 was required in 0.43% of the French treatment initiators, not significantly different from the 0.34% rate in patients on maintenance systemic therapy. A study limitation was the lack of a control group.

Nonetheless, the data did answer the investigators’ main question: “This is the first data showing no increased incidence of severe COVID-19 in psoriasis patients receiving systemic therapy in the treatment initiation period compared to those on maintenance therapy. This may now allow physicians to initiate conventional systemic or biologic therapy in patients with severe psoriasis on a case-by-case basis in the context of the persistent COVID-19 pandemic,” Dr. Fougerousse concluded.


 

Proposed mechanism of benefit

The Italian study findings that biologics boost the risk of infection with the SARS-CoV-2 virus in psoriasis patients while potentially protecting them against ICU admission and death are backed by a biologically plausible albeit as yet unproven mechanism of action, Dr. Damiani asserted.

He elaborated: A vast body of high-quality clinical trials data demonstrates that these targeted immunosuppressive agents are associated with modestly increased risk of viral infections, including both skin and respiratory tract infections. So there is no reason to suppose these agents would offer protection against the first phase of COVID-19, involving SARS-CoV-2 infection, nor protect against the second (pulmonary phase), whose hallmarks are dyspnea with or without hypoxia. But progression to the third phase, involving hyperinflammation and hypercoagulation – dubbed the cytokine storm – could be a different matter.

“Of particular interest was that our patients on IL-17 inhibitors displayed a really great outcome. Interleukin-17 has procoagulant and prothrombotic effects, organizes bronchoalveolar remodeling, has a profibrotic effect, induces mitochondrial dysfunction, and encourages dendritic cell migration in peribronchial lymph nodes. Therefore, by antagonizing this interleukin, we may have a better prognosis, although further studies are needed to be certain,” Dr. Damiani commented.
 

Publication of his preliminary findings drew the attention of a group of highly respected thought leaders in psoriasis, including James G. Krueger, MD, head of the laboratory for investigative dermatology and codirector of the center for clinical and investigative science at Rockefeller University, New York.

The Italian report prompted them to analyze data from the phase 4, double-blind, randomized ObePso-S study investigating the effects of the IL-17 inhibitor secukinumab (Cosentyx) on systemic inflammatory markers and gene expression in psoriasis patients. The investigators demonstrated that IL-17–mediated inflammation in psoriasis patients was associated with increased expression of the angiotensin-converting enzyme 2 (ACE2) receptor in lesional skin, and that treatment with secukinumab dropped ACE2 expression to levels seen in nonlesional skin. Given that ACE2 is the chief portal of entry for SARS-CoV-2 and that IL-17 exerts systemic proinflammatory effects, it’s plausible that inhibition of IL-17–mediated inflammation via dampening of ACE2 expression in noncutaneous epithelia “could prove to be advantageous in patients with psoriasis who are at risk for SARS-CoV-2 infection,” according to Dr. Krueger and his coinvestigators in the Journal of Allergy and Clinical Immunology.

Dr. Damiani and Dr. Fougerousse reported having no financial conflicts regarding their studies. The secukinumab/ACE2 receptor study was funded by Novartis.
 

bjancin@mdedge.com

Biologic therapy for psoriasis may protect against severe COVID-19, according to two large observational studies from Italy and France presented at the virtual annual congress of the European Academy of Dermatology and Venereology.

“Biologics seem to be very protective against severe, poor-prognosis COVID-19, but they do not prevent infection with the virus,” reported Giovanni Damiani, MD, a dermatologist at the University of Milan.

This apparent protective effect of biologic agents against severe and even fatal COVID-19 is all the more impressive because the psoriasis patients included in the Italian study – as is true of those elsewhere throughout the world – had relatively high rates of obesity, smoking, and chronic obstructive pulmonary disease, known risk factors for severe COVID-19, he added.

He presented a case-control study including 1,193 adult psoriasis patients on biologics or apremilast (Otezla) at Milan’s San Donato Hospital during the period from Feb. 21 to April 9, 2020. The control group comprised more than 10 million individuals, the entire adult population of the Lombardy region, of which Milan is the capital. This was the hardest-hit area in all of Italy during the first wave of COVID-19.

Twenty-two of the 1,193 psoriasis patients experienced confirmed COVID-19 during the study period. Seventeen were quarantined at home because their disease was mild. Five were hospitalized. But no psoriasis patients were placed in intensive care, and none died.

Psoriasis patients on biologics were significantly more likely than the general Lombardian population to test positive for COVID-19, with an unadjusted odds ratio of 3.43. They were at 9.05-fold increased risk of home quarantine for mild disease, and at 3.59-fold greater risk than controls for hospitalization for COVID-19. However, they were not at significantly increased risk of ICU admission. And while they actually had a 59% relative risk reduction for death, this didn’t achieve statistical significance.

Forty-five percent of the psoriasis patients were on an interleukin-17 (IL-17) inhibitor, 22% were on a tumor necrosis factor–alpha inhibitor, and 20% were taking an IL-12/23 inhibitor. Of note, none of 77 patients on apremilast developed COVID-19, even though it is widely considered a less potent psoriasis therapy than the injectable monoclonal antibody biologics.

The French experience

Anne-Claire Fougerousse, MD, and her French coinvestigators conducted a study designed to address a different question: Is it safe to start psoriasis patients on biologics or older conventional systemic agents such as methotrexate during the pandemic?

She presented a French national cross-sectional study of 1,418 adult psoriasis patients on a biologic or standard systemic therapy during a snapshot in time near the peak of the first wave of the pandemic in France: the period from April 27 to May 7, 2020. The group included 1,188 psoriasis patients on maintenance therapy and 230 who had initiated systemic treatment within the past 4 months. More than one-third of the patients had at least one risk factor for severe COVID-19.

Although testing wasn’t available to confirm all cases, 54 patients developed probable COVID-19 during the study period. Only five required hospitalization. None died. The two hospitalized psoriasis patients admitted to an ICU had obesity as a risk factor for severe COVID-19, as did another of the five hospitalized patients, reported Dr. Fougerousse, a dermatologist at the Bégin Military Teaching Hospital in Saint-Mandé, France. Hospitalization for COVID-19 was required in 0.43% of the French treatment initiators, not significantly different from the 0.34% rate in patients on maintenance systemic therapy. A study limitation was the lack of a control group.

Nonetheless, the data did answer the investigators’ main question: “This is the first data showing no increased incidence of severe COVID-19 in psoriasis patients receiving systemic therapy in the treatment initiation period compared to those on maintenance therapy. This may now allow physicians to initiate conventional systemic or biologic therapy in patients with severe psoriasis on a case-by-case basis in the context of the persistent COVID-19 pandemic,” Dr. Fougerousse concluded.


 

Proposed mechanism of benefit

The Italian study findings that biologics boost the risk of infection with the SARS-CoV-2 virus in psoriasis patients while potentially protecting them against ICU admission and death are backed by a biologically plausible albeit as yet unproven mechanism of action, Dr. Damiani asserted.

He elaborated: A vast body of high-quality clinical trials data demonstrates that these targeted immunosuppressive agents are associated with modestly increased risk of viral infections, including both skin and respiratory tract infections. So there is no reason to suppose these agents would offer protection against the first phase of COVID-19, involving SARS-CoV-2 infection, nor protect against the second (pulmonary phase), whose hallmarks are dyspnea with or without hypoxia. But progression to the third phase, involving hyperinflammation and hypercoagulation – dubbed the cytokine storm – could be a different matter.

“Of particular interest was that our patients on IL-17 inhibitors displayed a really great outcome. Interleukin-17 has procoagulant and prothrombotic effects, organizes bronchoalveolar remodeling, has a profibrotic effect, induces mitochondrial dysfunction, and encourages dendritic cell migration in peribronchial lymph nodes. Therefore, by antagonizing this interleukin, we may have a better prognosis, although further studies are needed to be certain,” Dr. Damiani commented.
 

Publication of his preliminary findings drew the attention of a group of highly respected thought leaders in psoriasis, including James G. Krueger, MD, head of the laboratory for investigative dermatology and codirector of the center for clinical and investigative science at Rockefeller University, New York.

The Italian report prompted them to analyze data from the phase 4, double-blind, randomized ObePso-S study investigating the effects of the IL-17 inhibitor secukinumab (Cosentyx) on systemic inflammatory markers and gene expression in psoriasis patients. The investigators demonstrated that IL-17–mediated inflammation in psoriasis patients was associated with increased expression of the angiotensin-converting enzyme 2 (ACE2) receptor in lesional skin, and that treatment with secukinumab dropped ACE2 expression to levels seen in nonlesional skin. Given that ACE2 is the chief portal of entry for SARS-CoV-2 and that IL-17 exerts systemic proinflammatory effects, it’s plausible that inhibition of IL-17–mediated inflammation via dampening of ACE2 expression in noncutaneous epithelia “could prove to be advantageous in patients with psoriasis who are at risk for SARS-CoV-2 infection,” according to Dr. Krueger and his coinvestigators in the Journal of Allergy and Clinical Immunology.

Dr. Damiani and Dr. Fougerousse reported having no financial conflicts regarding their studies. The secukinumab/ACE2 receptor study was funded by Novartis.
 

bjancin@mdedge.com

Biologic therapy for psoriasis may protect against severe COVID-19, according to two large observational studies from Italy and France presented at the virtual annual congress of the European Academy of Dermatology and Venereology.

“Biologics seem to be very protective against severe, poor-prognosis COVID-19, but they do not prevent infection with the virus,” reported Giovanni Damiani, MD, a dermatologist at the University of Milan.

This apparent protective effect of biologic agents against severe and even fatal COVID-19 is all the more impressive because the psoriasis patients included in the Italian study – as is true of those elsewhere throughout the world – had relatively high rates of obesity, smoking, and chronic obstructive pulmonary disease, known risk factors for severe COVID-19, he added.

He presented a case-control study including 1,193 adult psoriasis patients on biologics or apremilast (Otezla) at Milan’s San Donato Hospital during the period from Feb. 21 to April 9, 2020. The control group comprised more than 10 million individuals, the entire adult population of the Lombardy region, of which Milan is the capital. This was the hardest-hit area in all of Italy during the first wave of COVID-19.

Twenty-two of the 1,193 psoriasis patients experienced confirmed COVID-19 during the study period. Seventeen were quarantined at home because their disease was mild. Five were hospitalized. But no psoriasis patients were placed in intensive care, and none died.

Psoriasis patients on biologics were significantly more likely than the general Lombardian population to test positive for COVID-19, with an unadjusted odds ratio of 3.43. They were at 9.05-fold increased risk of home quarantine for mild disease, and at 3.59-fold greater risk than controls for hospitalization for COVID-19. However, they were not at significantly increased risk of ICU admission. And while they actually had a 59% relative risk reduction for death, this didn’t achieve statistical significance.

Forty-five percent of the psoriasis patients were on an interleukin-17 (IL-17) inhibitor, 22% were on a tumor necrosis factor–alpha inhibitor, and 20% were taking an IL-12/23 inhibitor. Of note, none of 77 patients on apremilast developed COVID-19, even though it is widely considered a less potent psoriasis therapy than the injectable monoclonal antibody biologics.

The French experience

Anne-Claire Fougerousse, MD, and her French coinvestigators conducted a study designed to address a different question: Is it safe to start psoriasis patients on biologics or older conventional systemic agents such as methotrexate during the pandemic?

She presented a French national cross-sectional study of 1,418 adult psoriasis patients on a biologic or standard systemic therapy during a snapshot in time near the peak of the first wave of the pandemic in France: the period from April 27 to May 7, 2020. The group included 1,188 psoriasis patients on maintenance therapy and 230 who had initiated systemic treatment within the past 4 months. More than one-third of the patients had at least one risk factor for severe COVID-19.

Although testing wasn’t available to confirm all cases, 54 patients developed probable COVID-19 during the study period. Only five required hospitalization. None died. The two hospitalized psoriasis patients admitted to an ICU had obesity as a risk factor for severe COVID-19, as did another of the five hospitalized patients, reported Dr. Fougerousse, a dermatologist at the Bégin Military Teaching Hospital in Saint-Mandé, France. Hospitalization for COVID-19 was required in 0.43% of the French treatment initiators, not significantly different from the 0.34% rate in patients on maintenance systemic therapy. A study limitation was the lack of a control group.

Nonetheless, the data did answer the investigators’ main question: “This is the first data showing no increased incidence of severe COVID-19 in psoriasis patients receiving systemic therapy in the treatment initiation period compared to those on maintenance therapy. This may now allow physicians to initiate conventional systemic or biologic therapy in patients with severe psoriasis on a case-by-case basis in the context of the persistent COVID-19 pandemic,” Dr. Fougerousse concluded.


 

Proposed mechanism of benefit

The Italian study findings that biologics boost the risk of infection with the SARS-CoV-2 virus in psoriasis patients while potentially protecting them against ICU admission and death are backed by a biologically plausible albeit as yet unproven mechanism of action, Dr. Damiani asserted.

He elaborated: A vast body of high-quality clinical trials data demonstrates that these targeted immunosuppressive agents are associated with modestly increased risk of viral infections, including both skin and respiratory tract infections. So there is no reason to suppose these agents would offer protection against the first phase of COVID-19, involving SARS-CoV-2 infection, nor protect against the second (pulmonary phase), whose hallmarks are dyspnea with or without hypoxia. But progression to the third phase, involving hyperinflammation and hypercoagulation – dubbed the cytokine storm – could be a different matter.

“Of particular interest was that our patients on IL-17 inhibitors displayed a really great outcome. Interleukin-17 has procoagulant and prothrombotic effects, organizes bronchoalveolar remodeling, has a profibrotic effect, induces mitochondrial dysfunction, and encourages dendritic cell migration in peribronchial lymph nodes. Therefore, by antagonizing this interleukin, we may have a better prognosis, although further studies are needed to be certain,” Dr. Damiani commented.
 

Publication of his preliminary findings drew the attention of a group of highly respected thought leaders in psoriasis, including James G. Krueger, MD, head of the laboratory for investigative dermatology and codirector of the center for clinical and investigative science at Rockefeller University, New York.

The Italian report prompted them to analyze data from the phase 4, double-blind, randomized ObePso-S study investigating the effects of the IL-17 inhibitor secukinumab (Cosentyx) on systemic inflammatory markers and gene expression in psoriasis patients. The investigators demonstrated that IL-17–mediated inflammation in psoriasis patients was associated with increased expression of the angiotensin-converting enzyme 2 (ACE2) receptor in lesional skin, and that treatment with secukinumab dropped ACE2 expression to levels seen in nonlesional skin. Given that ACE2 is the chief portal of entry for SARS-CoV-2 and that IL-17 exerts systemic proinflammatory effects, it’s plausible that inhibition of IL-17–mediated inflammation via dampening of ACE2 expression in noncutaneous epithelia “could prove to be advantageous in patients with psoriasis who are at risk for SARS-CoV-2 infection,” according to Dr. Krueger and his coinvestigators in the Journal of Allergy and Clinical Immunology.

Dr. Damiani and Dr. Fougerousse reported having no financial conflicts regarding their studies. The secukinumab/ACE2 receptor study was funded by Novartis.
 

bjancin@mdedge.com