Clinical Question

What are the most effective treatments for moderate to severe plaque psoriasis?

Evidence-Based Answer

Infliximab, bimekizumab (Bimzelx), ixekizumab (Taltz), and risankizumab (Skyrizi) are the most effective medications for achieving a 90% reduction in symptoms among patients with moderate to severe plaque psoriasis.¹ (Strength of Recommendation: A, consistent, good-quality patient-oriented evidence.)

Practice Pointers

Psoriasis is a chronic, immune-mediated inflammatory disorder involving the skin and other organ systems. It affects an estimated 3.2% of people older than 20 years in the United States.² Psoriasis can present significant challenges due to its variable clinical manifestations, potential for comorbidities, and the evolving landscape of treatment options.³

This Cochrane review included 179 randomized controlled trials with a total of 62,339 participants and evaluated 20 unique treatments.¹ The patient population included adults older than 18 years with moderate to severe plaque psoriasis. The Psoriasis Area and Severity Index (PASI) score was used to assess psoriasis severity (range = 0 to 72, with a score of 5 to 10 indicating moderate disease and a score greater than 10 indicating severe disease). The PASI instrument is completed by examiners, and the score considers the extent and severity of skin involvement, including factors such as redness, scaling, and thickness of psoriatic lesions in four body regions (i.e., head, upper extremities, trunk, and lower extremities). PASI 90 describes when a patient has symptoms of psoriasis that have improved by 90% or more compared with their initial baseline PASI score and is, therefore, a measure of treatment effectiveness. Of the studies included in this review, 56% were placebo-controlled, and at least 77% were industry-sponsored.

The participants' average PASI score at baseline was 20.4 (range = 9.5 to 39). A network meta-analysis demonstrated that, compared with placebo, all interventions at the class level (e.g., nonbiologic systemic agents, small molecules, biologic treatments) helped more patients reach PASI 90. Compared with those using the nonbiologic systemic agents, more patients using the biologic treatments (i.e., anti-IL17, anti-IL12/23, anti-IL23, and anti–tumor necrosis factor alpha) reached PASI 90. Anti-IL17 treatments (i.e., brodalumab [Siliq], bimekizumab, ixekizumab, and secukinumab [Cosentyx]) helped more patients reach PASI 90 than other interventions. Compared with placebo, the most effective drugs for reaching PASI 90 were infliximab (risk ratio [RR] = 49.16; 95% CI, 20.49 to 117.95), bimekizumab (RR = 27.86; 95% CI, 23.56 to 32.94), ixekizumab (RR = 27.35; 95% CI, 23.15 to 32.29), and risankizumab (RR = 26.16; 95% CI, 22.03 to 31.07). When compared with each other, these medications had similar clinical effectiveness. Serious adverse events analysis was based on a very low number of events with low to moderate evidence; however, none of the interventions increased the risk of serious adverse events compared with placebo.

Limitations of this review were that the trials assessed benefit during the induction treatment phase (from eight to 24 weeks), and the studies may have been of insufficient duration to detect rare or long-term adverse effects. It was also noted that there was variation in how well the studies took measures to blind investigators and participants; one-third of the trials in the review were at high or unclear risk of performance bias.

This Cochrane review supports the use of infliximab, bimekizumab, ixekizumab, and risankizumab to treat moderate to severe plaque psoriasis. These findings align with current recommendations from the American Academy of Dermatology, the National Psoriasis Foundation, and the National Institute for Health and Care Excellence.^4,5 Further study is needed to better evaluate long-term adverse effects and safety data of the systemic treatments for psoriasis and to allow subgroup analysis on patient groups such as those who had been treated previously and those with obesity, serious comorbidities, different durations of illness, and the presence of complications such as arthritis. Further assessment is also needed to determine the value of nonbiologic systemic treatments.

The practice recommendations in this activity are available at https://www.cochrane.org/CD011535.