New Topical MOAs for Psoriasis Treatment Show Promise for ‘Major Unmet Medical Need’
The last time we had a new mechanism of action approved for topical use in psoriasis the movie “Titanic” was setting box office records and we were cranking Chumbawamba on our Sony Discmans. The year was 1997 and the drug was tazarotene gel.
Since then, we have had 14 systemic treatments approved for psoriasis; however, there has been virtually no innovation in topical therapy beyond better vehicles and combination products, despite the fact that virtually all psoriasis patients will require topical treatment at some point.
Our current arsenal is dominated by topical steroids, which are limited by skin atrophy; topical calcineurin inhibitors, which are used off label and carry black box warnings for cancer; vitamin D analogues, which have modest efficacy and are primarily used in a steroid sparing mode; and vitamin A analogues, which are limited by modest efficacy, irritation and are contraindicated in pregnancy.
Recent studies have linked chronic use of topical steroids to diabetes and use of high cumulative amounts of potent or very potent topical steroids to major osteoporotic fracture. While the causal relationship between topical steroid use and outcomes such as diabetes and fracture is not established, clearly we have a major unmet medical need for new approaches to the topical management of psoriasis.
With this treatment gap in mind, this issue of Healio Psoriatic Disease is dedicated to long overdue advances in the topical management of psoriasis. Two new mechanisms of action (MOAs) appear highly promising for use in the clinic.
Tapinarof is an aryl hydrocarbon receptor modulating agent. In phase 3 clinical trials, a Physician Global Assessment score of clear or almost clear, with at least a 2-grade improvement from baseline, was found in 35.4% and 40.2% of patients treated with tapinarof cream once daily compared with 6% and 6.3% of those treated with vehicle cream. Contact dermatitis and folliculitis occurred in 11% and 5% of patients.
Roflumilast is a PDE4 inhibitor and is currently approved in pill form for the treatment of severe chronic obstructive pulmonary disease. At week 8, Investigator Global Assessment scores of clear or almost clear were reported in 42.4% and 37.5% of patients treated once daily with roflumilast foam compared with 6.1% and 6.8% of patients treated with vehicle. It also appeared to be well tolerated without irritation.
Phase 3 trials, however, tend to provoke more questions than they answer. The first key question is how well these topical agents will work under real world conditions where patient adherence may be especially challenging. This measure is considered “effectiveness” as opposed to efficacy which is measured in clinical trials.
Of particular importance is whether these new treatments will offer similar effectiveness to potent topical steroids, but with no concerns for long term use — the holy grail of topical psoriasis management, where one prescription can be used effectively and safely anywhere on the body for psoriasis, from the scalp to the face, the genitals to the elbows, the palms to the soles.
The second key question: What percent of the body surface area can be treated and are there risks associated with systemic absorption? Third, will there be any long-term risks associated with chronic use of these new MOAs? And finally, will these novel topical agents be accessible to our patients, or will they require lengthy prior authorization steps that will prove insurmountable to patients and clinicians?
Stay tuned to Healio Psoriatic Disease as we seek answers to these important questions. I am eager to get the answer to these questions myself, and I am looking forward to getting experience with these new topical MOAs in my practice.
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