Editors' ChoiceImmunotherapy

Clearing up psoriasis

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Science Translational Medicine  14 Oct 2015:
Vol. 7, Issue 309, pp. 309ec174
DOI: 10.1126/scitranslmed.aad4444

Rheumatology is at the brink of a new era in precision medicine with the emergence of biological therapies for autoimmune diseases that target specific inflammatory pathways. Signaling by interleukin 17A (IL-17)—a cytokine prominently secreted by IL-17–producing T helper (TH17) cells—has been implicated in multiple inflammatory conditions, including psoriasis, by animal models and human genetics. Indeed, monoclonal antibodies inhibiting this pathway have shown promise in clinical trials. Now, results from phase 3 clinical trials reported in two recent studies further confirm the pathogenic role of IL-17 signaling in psoriasis and the therapeutic efficacy of IL-17 pathway blockade.

Both studies report on the clinical efficacy of monoclonal antibodies that inhibit IL-17 signaling for the treatment of psoriasis and psoriatic arthritis. Lebwohl et al. studied treatment of psoriasis with brodalumab, which binds to a subunit of the IL-17 receptor and blocks signaling downstream of IL-17. They report data from two randomized control trials comparing treatment with brodalumab to placebo or an FDA-approved biological treatment—ustekinumab—that targets a protein subunit shared by IL-12 and IL-23. Brodalumab achieved the trials’ primary endpoints after 12 weeks of treatment, demonstrating clinical superiority to both placebo and ustekinumab. At the highest doses of brodalumab, more than 50% of patients achieved complete clearance of skin disease at the end of 52 weeks. In the second study, Mease et al. report data from a randomized control trial of psoriatic arthritis. They inhibited IL-17 signaling with secukinumab, a human monoclonal antibody that neutralizes IL-17A. Secukinumab improved both skin lesions and arthritis in these patients compared with placebo. Furthermore, secukinumab was also effective in some patients who had previously discontinued use of tumor necrosis factor (TNF) inhibitors, commonly used to treat psoriatic arthritis, due to poor response or side effects.

These studies show that anti–IL-17 signaling agents are likely to play a central role in the treatment of psoriasis and psoriatic arthritis, yet considerable work lies ahead to understand which pathogenic cytokine pathways—and which components of a pathway—could be targeted to treat other autoimmune diseases. As we learn more about why not all psoriasis patients respond to IL-17 pathway blockade, future efforts might even move toward approaches personalized to each patient’s pathogenic cytokine profile, expanding our arsenal of targeted anti-cytokine therapies for autoimmune diseases.

M. Lebwohl et al., Phase 3 studies comparing brodalumab with ustekinumab in psoriasis. N. Engl. J. Med. 373, 1318–1328 (2015). [Abstract]

P. J. Mease et al., Secukinumab inhibition of interleukin-17A in patients with psoriatic arthritis. N. Engl. J. Med. 373, 1329–1339 (2015). [Abstract]

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