Psoriasis - Emerging treatments

Tapinarof

Tapinarof, a small-molecule topical aryl hydrocarbon receptor (AhR) agonist, is the first topical novel chemical entity (corticosteroid-free) treatment to be approved by the US Food and Drug Administration (FDA) in 25 years for adults with any severity of plaque psoriasis. Two identical phase 3 randomised controlled trials demonstrated tapinarof significantly reduced the severity of plaque psoriasis, compared with vehicle, in patients with mild to severe plaque psoriasis at 12 weeks.[118] Patients who completed the 12-week trial were eligible to be included in a 40-week phase 3 open-label trial with a 4-week follow up.[119] The trial reported that 41% of patients achieved complete disease clearance (physician global assessment [PGA] score 0) and that 58% of patients who entered the trial with PGA ≥2 achieved PGA of 0 or 1. The mean duration of remission for patients who achieved PGA 0 was 130 days. The most frequent adverse effects were folliculitis, contact dermatitis, and upper respiratory tract infection.[119]

Tofacitinib

Tofacitinib, an oral Janus kinase inhibitor, is approved for use in patients with psoriatic arthritis and has been evaluated in phase 3 randomised controlled trials of patients with moderate to severe chronic plaque psoriasis.[120][121][122] Systematic reviews conclude that tofacitinib is effective in reducing signs and symptoms of chronic plaque psoriasis.[123][124] Tofacitinib appeared to be associated with an increased risk for infection (including serious infections and herpes zoster) in some studies.[120][122][123]

Deucravacitinib

Deucravacitinib, a first-in-class oral selective tyrosine kinase 2 (TYK2) inhibitor, has been approved by the FDA to treat moderate to severe plaque psoriasis in adults. Deucravacitinib improved clearing of psoriasis compared with placebo in two phase 3, double-blind, randomised controlled trials in patients with moderate to severe plaque psoriasis at 16 and 24 weeks.[125][126] Efficacy continued to improve after 24 weeks, with 82% of patients who achieved Psoriasis Area and Severity Index (PASI) score of 75 with deucravacitinib at week 24 maintaining their response at week 52 in the first trial.[125] The second of the two phase 3 trials included a randomised withdrawal and retreatment after week 24, 80% of patients who continued with deucravacitinib maintained PASI 75 response compared with 31% of patients who were withdrawn.[126] The results of the trials were limited by a lack of cultural diversity, further phase 3 trials are underway.[127]

Bimekizumab

Bimekizumab, an immunoglobulin G1 monoclonal antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A and IL-17AF, is approved in Europe for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy. The FDA is currently reviewing an application for approval. In patients with moderate to severe psoriasis, treatment with bimekizumab resulted in greater skin clearance than treatment with secukinumab over 16 and 48 weeks; bimekizumab was associated with oral candidiasis.[128] A study on the 2-year safety profile of bimekizumab reported that the treatment was well tolerated with no increase in adverse effects with longer treatment duration for patients with plaque psoriasis, apart from an increased risk of mild to moderate oral candidiasis.[129]

Spesolimab

Spesolimab, a monoclonal antibody that inhibits the activation of the interleukin-36 receptor (IL-36R), is the first FDA-approved treatment specifically to treat generalised pustular psoriasis (GPP) flares in adults. The approval is based on the results of one phase 2 randomised controlled trial which demonstrated that spesolimab significantly increased lesion clearance at one week compared with placebo in patients with GPP.[130] Infections occurred in 47% of patients treated with spesolimab at 12 weeks, and anti-drug antibodies were detected in 46% of the patients treated with spesolimab. Longer and larger trials are needed to identify the efficacy and risks of spesolimab treatment.[130]

Roflumilast

Roflumilast, a topical phosphodiesterase type 4 (PDE-4) inhibitor, is approved by the FDA for the treatment of plaque psoriasis. A phase 2b, double-blind randomised controlled trial demonstrated that roflumilast significantly improved disease clearance at 6 weeks, compared with vehicle, in patients with plaque psoriasis.[131] Further trials are needed.