expert roundtables

Newer and Pipeline Therapies and Biologics for Plaque Psoriasis

by Boni E. Elewski, MD; Steven R. Feldman, MD, PhD; and Bruce E. Strober, MD, PhD

Overview

Recent progress in targeted biologic therapies for plaque psoriasis reflects an understanding of the crucial role of the interleukin-23 (IL-23)/IL-17 axis in the pathogenesis of this disease. Seeking to build on this progress, researchers have developed several new biologics and small molecules that are now being evaluated in clinical trials.

Q:

What are your thoughts on the new targeted therapies that are in development for plaque psoriasis?

Boni E. Elewski, MD

James Elder Endowed Professor and Chair of Graduate Medical Education
Department of Dermatology
University of Alabama
Birmingham, AL

“Although they work fast, the IL-17A inhibitors may lose efficacy over time, and treating psoriasis is a marathon, not a sprint. So, I am excited about bimekizumab because it maintained its response throughout the entire treatment period.”

Boni E. Elewski, MD

There are still unmet needs in psoriasis, particularly in disease manifestations. Although they work fast, the IL-17A inhibitors may lose efficacy over time, and treating psoriasis is a marathon, not a sprint. So, I am excited about bimekizumab because it maintained its response throughout the entire treatment period. Bimekizumab inhibits both IL-17A and IL-17F, whereas IL-17 inhibitors such as secukinumab and ixekizumab only inhibit IL-17A. In the BE READY study, 91% of patients receiving bimekizumab 320 mg every 4 weeks achieved Psoriasis Area and Severity Index (PASI 90) at week 16; responses were maintained through week 56 with maintenance doses given every 4 weeks or every 8 weeks.

Another unmet need is that the oral drugs such as apremilast are not as efficacious as injectable drugs for psoriasis. Deucravacitinib is an emerging oral drug that targets the Janus kinase pathway, and I think that it is very exciting because it seems to have the efficacy of the injectable drugs but in an oral form.

There are manifestations that are difficult to treat and can take, say, 6 months to clear (eg, psoriasis and palmoplantar pustulosis), so this is another area for which new therapies would be welcome. I have had some success with currently available treatments, but palmoplantar psoriasis and palmoplantar pustulosis can both be very stubborn, and you must let the patient know that it could take some time to resolve. Upregulation of the IL-36 pathway is reported in pustular psoriasis—in generalized pustular psoriasis and in palmoplantar psoriasis—so there is interest in targeting this pathway, and an anti–IL-36 receptor monoclonal antibody is being tested.

Steven R. Feldman, MD, PhD

Professor of Dermatology, Pathology, Social Sciences & Health Policy, and Molecular Medicine & Translational Science
Wake Forest School of Medicine
Winston-Salem, NC

“The safety of new drugs is always a concern to me; I like to see long-term efficacy and safety data. However, I will prescribe newer treatments immediately when needed for patients who have failed with older agents.”

Steven R. Feldman, MD, PhD

Tumor necrosis factor (TNF) blockers revolutionized the management of psoriasis, but these drugs also have some potential adverse effects. Newer biologic drugs that target the IL-23/IL-17 axis are as or more effective than TNF blockers and are safer, too. IL-17A and IL-23 are key mechanistic drivers of the immunopathogenesis of psoriasis. Available drugs targeting IL-17 include secukinumab, ixekizumab, and brodalumab. Available drugs selectively targeting the IL-23 pathway include ustekinumab, guselkumab, risankizumab, and tildrakizumab. Both IL-17 and IL-23 inhibitors are well tolerated, and some provide skin clearance that is superior to that of most currently approved TNF inhibitors, with complete or near complete skin clearance observed in the majority of patients.

The safety of new drugs is always a concern to me; I like to see long-term efficacy and safety data. However, I will prescribe newer treatments immediately when needed for patients who have failed with older agents. I think that bimekizumab has a chance to be the most effective treatment that we have for plaque psoriasis. If a patient wants to be completely clear, it is a great choice, especially for those who have failed with existing options.

Bruce E. Strober, MD, PhD

Clinical Professor, Department of Dermatology
Yale University School of Medicine
New Haven, CT
Central Connecticut Dermatology
Cromwell, CT

“I agree that bimekizumab is an exciting drug, and it might really set a new standard for efficacy for both short- and long-term treatment.” 

Bruce E. Strober, MD, PhD

I agree that bimekizumab is an exciting drug, and it might really set a new standard for efficacy for both short- and long-term treatment. It is a first-in-class, fast-acting monoclonal antibody that is designed to simultaneously target IL-17A and IL-17F. Bimekizumab was recently approved in Europe for the treatment of moderate to severe plaque psoriasis and is currently being reviewed for approval in the United States.

Sonelokimab is a novel, trivalent, tandem nanobody targeting both IL-17A and IL-17F. It showed significant clinical benefit over placebo and had an acceptable safety profile in a phase 2b study in patients with plaque psoriasis. It might be a drug that you could use in psoriasis, psoriatic arthritis, and hidradenitis suppurativa, so that would be, perhaps, the one biologic on the horizon that I would look out for.

Janus kinase inhibitors will likely be the most effective class of drugs for palmoplantar psoriasis. I do not find that any of the biologics are remarkably effective in palmoplantar psoriasis; however, I do believe that methotrexate works well, and I often use it first line. Some people advocate for acitretin, but I think that it has too many side effects when used at efficacious doses, and you cannot use it in women of childbearing age.

References

Bellinato F, Gisondi P, Girolomoni G. Latest advances for the treatment of chronic plaque psoriasis with biologics and oral small molecules. Biologics2021;15:247-253. doi:10.2147/btt.S290309

Ceccarelli M, Venanzi Rullo E, Berretta M, et al. New generation biologics for the treatment of psoriasis and psoriatic arthritis. State of the art and considerations about the risk of infection. Dermatol Ther. 2021;34(1):e14660. doi:10.1111/dth.14660

Gordon KB, Foley P, Krueger JG, et al. Bimekizumab efficacy and safety in moderate to severe plaque psoriasis (BE READY): a multicentre, double-blind, placebo-controlled, randomised withdrawal phase 3 trial [published correction appears in Lancet. 2021;397(10280):1182]. Lancet. 2021;397(10273):475-486. doi:10.1016/S0140-6736(21)00126-4

Honma M, Hayashi K. Psoriasis: recent progress in molecular-targeted therapies. J Dermatol. 2021;48(6):761-777. doi:10.1111/1346-8138.15727

Iznardo H, Puig L. Dual inhibition of IL-17A and IL-17F in psoriatic disease. Ther Adv Chronic Dis. 2021;12:20406223211037846. doi:10.1177/20406223211037846

Menter A, Krueger GG, Paek SY, Kivelevitch D, Adamopoulos IE, Langley RG. Interleukin-17 and interleukin-23: a narrative review of mechanisms of action in psoriasis and associated comorbidities. Dermatol Ther (Heidelb). 2021;11(2):385-400. doi:10.1007/s13555-021-00483-2

Mrowietz U, Burden AD, Pinter A, et al. Spesolimab, an anti-interleukin-36 receptor antibody, in patients with palmoplantar pustulosis: results of a phase IIa, multicenter, double-blind, randomized, placebo-controlled pilot study. Dermatol Ther (Heidelb). 2021;11(2):571-585. doi:10.1007/s13555-021-00504-0

Papp K, Gordon K, Thaçi D, et al. Phase 2 trial of selective tyrosine kinase 2 inhibition in psoriasis. N Engl J Med. 2018;379(14):1313-1321.doi:10.1056/NEJMoa1806382

Papp KA, Weinberg MA, Morris A, Reich K. IL17A/F nanobody sonelokimab in patients with plaque psoriasis: a multicentre, randomised, placebo-controlled, phase 2b study [published correction appears in Lancet. 2021;397(10290):2150]. Lancet. 2021;387(10284):1564-1575. doi:10.1016/S0140-6736(21)00440-2.

Reich K, Papp KA, Blauvelt A, et al. Bimekizumab versus ustekinumab for the treatment of moderate to severe plaque psoriasis (BE VIVID): efficacy and safety from a 52-week, multicentre, double-blind, active comparator and placebo controlled phase 3 trial. Lancet. 2021;397(10273):487-498. doi:10.1016/S0140-6736(21)00125-2

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

Yamamoto T. Similarity and difference between palmoplantar pustulosis and pustular psoriasis. J Dermatol. 2021;48(6):750-760. doi:10.1111/1346-8138.15826

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