Dr. Alice Gottlieb discusses the science behind recently approved therapies for psoriasis, including their mechanisms of action and efficacy.
Alice Gottlieb, MD, PhD, Medical Director of Dermatology, Mount Sinai in New York City, New York.
“I presented a summary of what is known about the interleukin (IL)-17 and -23 blockers, and introduced bimekizumab (not yet approved), an IL-17A and IL-17F blocker. Inhibiting ‘F’ probably matters because in comparator studies published in the New England Journal of Medicine, bimekizumab beat secukinumab, an IL-17A blocker, in psoriasis clearing and beat adalimumab, a tumor necrosis factor (TNF) blocker,”1,2 said Alice Gottlieb, MD, PhD, who presented “What’s New In Psoriasis,” at the Masterclasses in Dermatology in Sarasota, Florida.
Still, IL-17 blockers ixekizumab and secukinumab are wonderful drugs, said Dr. Gottlieb.
“They work as well in psoriatic arthritis as adalimumab does, but they work better in the skin. They inhibit radiographic progression to an equal extent as adalimumab in the joints. They work on axial psoriatic arthritis, skin, nails, dactylitis, and enthesitis.”
IL-23 inhibitors guselkumab, risankizumab, and tildrakizumab offer the advantage of infrequent dosing, said Dr. Gottlieb.
According to Dr. Gottlieb, the FDA approved an adalimumab biosimilar for plaque psoriasis and other indications—the first of many such approvals expected. For dermatologists, this means pharmacists can substitute this biosimilar without asking the doctor because there are studies that show that it is interchangeable with the brand name adalimumab.
“I also talked about generalized pustular psoriasis and the fact that we now have [an FDA-approved] drug that really works well, called spesolimab. It is an IL-36 receptor monoclonal antibody that within a week can make all the pustules go away. It is given by intravenous (IV) infusion, 900 mg in one sitting, and you can repeat it a week later if you don’t get perfect results.”
Use of biologics has been shown to be better than conventional oral medications in preventing psoriatic arthritis, according to Dr. Gottlieb, who cited a study by Rosenthal et al.3
Oral Treatment Update
The newly approved TYK2 inhibitor deucravacitinib is an exciting option for psoriasis patients, said Dr. Gottlieb.
“Deucravacitinib does not have the side effects associated with Janus kinase (JAK) inhibitors. It works better than apremilast in psoriasis.”
Data for upadacitinib, a traditional JAK inhibitor approved for psoriatic arthritis, show the drug not only controls signs and symptoms of the disease but also inhibits radiographic progression of psoriatic arthritis, said Dr. Gottlieb.
Apremilast is now FDA approved for mild to moderate psoriasis, she said.
Safety Concerns with Methotrexate
Dr. Gottlieb discussed the controversy between rheumatologists and dermatologists regarding methotrexate use and its association with increased liver disease risk.
“Rheumatologists do not monitor as carefully for liver disease as we [dermatologists] do in psoriasis. Indeed, Joel Gelfand and his group showed that rheumatoid arthritis patients are different than psoriasis patients, and psoriasis patients [treated with methotrexate] have a higher incidence of liver fibrosis and cirrhosis compared with rheumatoid arthritis patients.4 Conservative monitoring for liver disease with methotrexate is warranted.”
Two New Topicals
There are two new topicals for psoriasis—both non-corticosteroids, said Dr. Gottlieb.
“One is roflumilast, a topical phosphodiesterase-4 inhibitor; the other is tapinarof, an aryl hydrocarbon receptor agonist. The advantage of those is they are not corticosteroids and do not thin the skin.”
In studies, both topicals showed roughly 40% of study participants achieved treatment success versus about 7% in the placebo group, she said.
“Roflumilast did a special study on intertriginous psoriasis, which is psoriasis in the warm, wet areas of the body, like under the breasts, where the legs meet the trunk, that sort of thing. And they showed no unusual toxicity. Roflumilast worked extremely well. Intertriginous psoriasis is tough to treat.”
References:
- Reich K, Warren RB, Lebwohl M, et al. Bimekizumab versus Secukinumab in Plaque Psoriasis. N Engl J Med. 2021;385(2):142-152. doi:10.1056/NEJMoa2102383.
- McInnes IB, Asahina A, Coates LC, et al. Bimekizumab in patients with psoriatic arthritis, naive to biologic treatment: a randomised, double-blind, placebo-controlled, phase 3 trial (BE OPTIMAL). Lancet. 2023;401(10370):25-37. doi:10.1016/S0140-6736(22)02302-9.
- Rosenthal YS, Schwartz N, Sagy I, et al. Incidence of Psoriatic Arthritis Among Patients Receiving Biologic Treatments for Psoriasis: A Nested Case-Control Study. Arthritis Rheumatol. 2022;74(2):237-243. doi:10.1002/art.41946.
- Gelfand JM, Wan J, Zhang H, et al. Risk of liver disease in patients with psoriasis, psoriatic arthritis, and rheumatoid arthritis receiving methotrexate: A population-based study. J Am Acad Dermatol. 2021;84(6):1636-1643. doi:10.1016/j.jaad.2021.02.019.
Disclosures: Dr. Gottlieb is an advisory board member, non-promotional speaker or consultant for Amgen, AnaptysBio, Avotres Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Dice Therapeutics, Dermavant, Eli Lilly, Janssen, Novartis, Pfizer, Sanofi, Sun Pharma, UCB Pharma, Xbiotech (stock options for a project). She has received research and educational grants from: AnaptysBio, Moonlake Immunotherapies, Novartis, BMS, and UCB Pharma. All funds go to the Icahn School of Medicine at Mount Sinai.