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Big Advances for Psoriasis

Op-Med is a collection of original articles contributed by Doximity members.

Normally at this time of year, the American Academy of Dermatology (AAD) holds the largest annual dermatology event in a major city such as San Francisco or Washington D.C. Over 10,000 people typically attend the meeting, including both dermatologists in the U.S. and internationally, residents and medical students, representatives from pharmaceutical, cosmeceutical, and device companies, publishers, patient advocacy groups, and other organizations. The AAD meeting is a vast and engaging educational and social experience. It is a great time to catch up with your colleagues and to network with various professionals. Last year the event was canceled at the last minute due to COVID-19.

This year the AAD meeting was hosted virtually and was entitled AAD VMX (Virtual Meeting Experience) from April 23 to 25. Attendees were able to stream over 75 sessions covering the full breadth of dermatology (medical, surgical, cosmetics), watch plenary speakers and late-breaking research presentations, browse more than 800 electronic posters, and visit more than 40 exhibitors. The content is available on-demand through July 12, 2021. The virtual meeting was very well-organized, and I was very appreciative to be part of it. However, despite the convenience of attending the meeting virtually at your home, nothing beats the physical presence of being at the meeting where you can feel the vibrancy and excitement. Because of COVID-19 and its aftermath, the virtual format most likely will not disappear but will be incorporated together with the live meeting as a hybrid for individuals who cannot attend the meeting in person. Also, the content from the meeting may still be available online for an indefinite period to rewatch a presentation or view one that you were not able to attend.

Because I specialize in the treatment of psoriasis and conduct numerous clinical trials, I was particularly interested in some of the most recent updates at AAD VMX on psoriasis.

During the past 20 years, there has been a remarkable evolution in the treatment of psoriasis. Previously, conventional systemic agents such as methotrexate, cyclosporine, acitretin, and other potent immunosuppressants, including 6-mercaptopurine and hydroxyurea, were utilized to treat moderate to severe plaque psoriasis. Another mainstay of treatment that was commonly employed was phototherapy, though the inconvenience and time commitment of having to come to a center several times per week was impractical for many patients. The advent of the biologic agents beginning with the TNF inhibitors 20 years ago started the revolution for more effective, predictable, and safer drugs to treat moderate to severe plaque psoriasis and psoriatic arthritis. Over the next two decades, new classes of biologic agents that target IL-12/IL-23, IL-17, and IL-23 have entered the market. The efficacy and safety of the later generation biologics have surpassed my expectations. We thought 50-75% clearance of psoriasis within 12-16 weeks was a good many years ago. Now we are talking about 90% or even 100% clearance as the new bar within that same time frame. The biologics that have been approved in the past few years have no warnings about serious infections, malignancies, organ toxicity, or major adverse cardiovascular events. In addition, a novel oral agent that targets phosphodiesterase-4 (PDE4) has been widely used by dermatologists for the past several years because of its safety profile and no routine requirement for laboratory monitoring.

There were a few products in the pipeline for the treatment of psoriasis that were noteworthy. While there are several oral agents available to treat psoriasis, a new oral agent with a different mechanism of action is always welcomed. The results of two phase 3 clinical trials for the efficacy and safety of deucravacitinib were presented. Deucravacitinib is an oral agent taken once a day and is a Tyk2 inhibitor in the Janus kinase (JAK) inhibitor class. The primary endpoint was at week 16, where over half the patients attained a 75% or greater improvement of their psoriasis based on the surface area on different locations of the body (arms, legs, trunk, head) and the reduction of redness, thickness, and scaling of the psoriatic plaques. Improvement of psoriasis continued after week 16. No significant safety signals were seen, and the black box warnings associated with JAK inhibitors such as serious infections, malignancies, deep vein thrombosis, pulmonary embolism were not evident. No laboratory abnormalities (metabolic and hematologic) were detected. There was a low incidence of folliculitis and acne seen in some of the patients. Overall, the efficacy and safety of Deucravacitinib seem comparable to a biologic agent such as a TNF inhibitor for psoriasis.

Head-to-head trials comparing agents in psoriasis are becoming more prevalent. Deucravacitinib showed superior efficacy to another oral agent, apremilast, at the primary endpoints. In another phase 3 trial, a novel biologic agent called bimekizumab demonstrated high 90% and 100% clearance rates at week 16 and was superior to another biologic agent, secukinumab. Both agents target IL-17A, but bimekizumab also targets IL-17F, which together contribute to the pathogenesis of psoriasis. Bimekizumab in previous trials also demonstrated superiority over adalimumab and ustekinumab. The safety of bimekizumab is comparable to other IL-17 inhibitors but does have a higher signal for oral candidiasis.

There is an unmet need for more effective topical non-steroidal agents to treat psoriasis. While topical steroids are the mainstay to treat psoriasis, prolonged usage can lead to adverse events such as atrophy of the skin, striae, and suppression of the HPA axis. Dermatologists would like a topical non-steroidal agent that has the efficacy comparable to at least a mid-potency steroid that is used for an extended period. In addition, such agents can be safely used in sensitive areas of the body such as the face, intertriginous areas, and the genital area. Two products in development are intriguing. One is topical roflumilast that is a PDE4 inhibitor, and the other is tapinarof which is an aryl hydrocarbon receptor modulating agent. Both seem to have the efficacy comparable to a mid-potency steroid and are well tolerated.

I look forward to attending live meetings again to engage with my colleagues and also appreciate the convenience of virtual programs. The paradigm may be a hybrid of both.

Image: SurfsUp / shutterstock

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