Biologic therapies, particularly interleukin (IL)-17 and IL-23 inhibitors, were associated with the highest likelihood of achieving near-complete skin clearance in patients with moderate to severe plaque psoriasis, while serious adverse events were similar across treatments.

In a Cochrane network meta-analysis of 160 randomized clinical trials including 57,611 patients with moderate to severe plaque psoriasis, April W. Armstrong, MD, of the University of California Los Angeles, and colleagues evaluated systemic pharmacologic treatments during the induction phase of 8 to 24 weeks. The primary outcomes were achievement of at least 90% improvement in Psoriasis Area and Severity Index (PASI 90) and the occurrence of serious adverse events.

All systemic therapies were more effective than placebo in achieving PASI 90 during the induction period. At the class level, IL-17 inhibitors ranked highest for efficacy, followed by IL-23, IL-12/23, and tumor necrosis factor (TNF) inhibitors. These biologics outperformed both targeted and nontargeted oral therapies and demonstrated a favorable balance of short-term efficacy and acceptability.

At the individual drug level, infliximab, a TNF inhibitor; bimekizumab, ixekizumab, brodalumab, and xeligekimab, IL-17 inhibitors; and risankizumab, an IL-23 inhibitor, ranked highest for PASI 90 response. Differences among these agents were small, suggesting broadly comparable short-term efficacy. The certainty of evidence was highest for bimekizumab. The strong ranking of infliximab likely reflects its potent immunologic activity, although its use may be limited by infusion requirements.

Serious adverse events were uncommon, with no meaningful differences detected between systemic treatments and placebo during the induction period.

Sensitivity analyses limited to approved dosing regimens showed shifts in treatment rankings, with brodalumab, guselkumab, and tildrakizumab ranking higher when nonapproved or exploratory doses were excluded. The inclusion of multiple trial phases and dosing regimens may influence comparative estimates, as earlier-phase studies can overestimate treatment effects.

Differences in onset of action were also observed: IL-17 inhibitors demonstrated more rapid responses, whereas IL-23 inhibitors showed more gradual improvements that may not be fully captured in short-term assessments. These findings reflect short-term outcomes, Dr Armstrong and colleagues noted, and may not fully represent longer-term differences, as IL-23 inhibitors may provide more durable responses over time.

Oral systemic therapies, including deucravacitinib and apremilast, demonstrated lower PASI 90 response rates compared with biologics but remain treatment options in patients who prefer oral therapy or who are not candidates for biologics because of comorbidities or access barriers.

The analysis was limited by its focus on short-term outcomes and its limited ability to assess long-term safety and effectiveness. Reporting of serious adverse events was infrequent and may not fully reflect overall tolerability.

Overall, the findings support biologic therapies, particularly IL-17 and IL-23 inhibitors, as the most effective options for short-term skin clearance in patients with moderate to severe plaque psoriasis and highlight their role in reshaping expectations for disease control.

Dr Armstrong reported relationships with multiple pharmaceutical companies, including AbbVie, Bristol Myers Squibb, Eli Lilly, Novartis, and Pfizer. Dr Merola reported personal fees from multiple pharmaceutical companies during the conduct of the study and outside the submitted work. No other disclosures were reported.

Source: JAMA Network