Quantitative Evaluation of Biologic Therapy Options for Psoriasis: A Systematic Review and Network Meta-Analysis

Abstract

Multiple biologic treatments are licensed for psoriasis. The lack of head-to-head randomized controlled trials makes choosing between them difficult for patients, clinicians, and guideline developers. To establish their relative efficacy and tolerability, we searched MEDLINE, PubMed, Embase, and Cochrane for randomized controlled trials of licensed biologic treatments for skin psoriasis. We performed a network meta-analysis to identify direct and indirect evidence comparing biologics with one another, methotrexate, or placebo. We combined this with hierarchical cluster analysis to consider multiple outcomes related to efficacy and tolerability in combination for each treatment. Study quality, heterogeneity, and inconsistency were evaluated. Direct comparisons from 41 randomized controlled trials (20,561 participants) were included. All included biologics were efficacious compared with placebo or methotrexate at 3-4 months. Overall, cluster analysis showed adalimumab, secukinumab, and ustekinumab were comparable in terms of high efficacy and tolerability. Ixekizumab and infliximab were differentiated by very high efficacy but poorer tolerability. The lack of longer term controlled data limited our analysis to short-term outcomes. Trial performance may not equate to real-world performance, and so results need to be considered alongside real-world, long-term safety and effectiveness data. These data suggest that it is possible to discriminate between biologics to inform clinical practice and decision making (PROSPERO 2015:CRD42015017538).

Figure 1

Flow diagram showing the identification of literature in the PRISMA format. RCT, randomized controlled trial.

Figure 2

Network maps for the main outcomes considered in the review. (a) Clear/nearly clear (minimal residual activity/PASI > 90/0 or 1 on PGA). (b) Mean change in the dermatology life quality index. (c) Withdrawal due to adverse events, all at 12 to 16 weeks. Nodes and edges are weighted according to number of studies including that treatment or comparison. ADA, adalimumab; ETA, etanercept; INF, infliximab; IXE, ixekizumab; MTX, methotrexate; PASI, psoriasis area and severity index; PBO, placebo; PGA, physician’s global assessment; SEC, secukinumab; UST, ustekinumab.

Figure 3

Plot of joint rankings based on hierarchical clustering of the surface under the cumulative ranking curve (SUCRA) estimates. Combined estimates of efficacy (clear/nearly clear—minimal residual activity/PASI > 90/0 or 1 on PGA) and tolerability (withdrawal due to adverse events) at 12 to 16 weeks. ADA, adalimumab; ETA, etanercept; INF, infliximab; IXE, ixekizumab; MTX, methotrexate; PASI, psoriasis area and severity index; PBO, placebo; PGA, physician’s global assessment; SEC, secukinumab; UST, ustekinumab.