Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis.
Level 1 - systematic review of randomized trials
Systematic review and network meta-analysis of randomized controlled trials
PubMed 37436070 · doi:10.1002/14651858.CD011535.pub6
What was done
A Cochrane living systematic review and network meta-analysis was updated through October 2022 to evaluate systemic pharmacological treatments (biologics, small molecules, and non-biologics) in adults with moderate-to-severe plaque psoriasis. The review synthesized randomized controlled trials comparing 20 active treatments against placebo or another active comparator. Primary outcomes were the proportion of participants achieving at least a 90% reduction in Psoriasis Area and Severity Index (PASI 90) and serious adverse events (SAEs) during the induction phase (8 to 24 weeks post-randomization). Treatment hierarchies were calculated using SUCRA, and evidence certainty was evaluated using CINeMA.
What was found
Across 179 RCTs (62,339 participants; mean age 44.6 years, 67.1% men, mean baseline PASI 20.4), all active classes outperformed placebo for PASI 90. Based on high-certainty evidence, the top-ranked drugs compared to placebo for PASI 90 were infliximab (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), with similar comparative performance among these four. Bimekizumab and ixekizumab were significantly more likely to achieve PASI 90 than secukinumab, while bimekizumab, ixekizumab, and risankizumab were superior to brodalumab and guselkumab. No significant difference was found between any intervention and placebo regarding SAE risk, although SAE findings relied on low event counts with very low- to moderate-certainty evidence.
Why it matters
This review provides a comprehensive comparative ranking of 20 systemic therapies for moderate-to-severe plaque psoriasis, establishing specific IL-17 inhibitors, IL-23 inhibitors, and infliximab as the most efficacious options for short-term skin clearance.
Limits
Evaluations were confined to the short-term induction phase (8 to 24 weeks), precluding long-term efficacy and safety conclusions. One-third of included trials (65/179) had high risk of bias, and 138/179 declared pharmaceutical company funding. Safety analysis had very low to moderate certainty due to low SAE counts. Quality-of-life data were poorly reported across trials, and the trial cohort had high baseline severity (mean PASI 20.4), which may limit generalizability to typical outpatient clinical populations.