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).

Biologic treatment sequences for plaque psoriasis: a cost-utility analysis based on 10 years of Dutch real-world evidence from BioCAPTURE

“…Several indirect comparisons in the form of a network meta‐analyses have been performed. These confirm that Ust is more efficacious than Eta but show no clear differences between Ada and Ust and between Ada and Eta …”

Matching-adjusted indirect comparison of efficacy in patients with moderate-to-severe plaque psoriasis treated with ixekizumab vs. secukinumab

“…Although an indirect comparison is not a replacement for a head‐to‐head trial, accuracy is improved when a common active comparator is used with a method such as the previously described matching‐adjusted indirect comparison (MAIC), which combines published and patient‐level data that are matched for baseline characteristics . Because the MAIC uses individual patient data (IPD), this approach is complementary to and can reduce biases found in network meta‐analyses (NMAs), which have limitations that have been described elsewhere . Matching on baseline characteristics helps to reduce imbalances from different trials that might impact the outcome (treatment effect modifiers) .…”

Subcutaneous methotrexate in patients with moderate-to-severe psoriasis: a critical appraisal

“…Given the apparent similarity in efficacy, it is unlikely that subcutaneous methotrexate would be cost‐effective when compared with oral methotrexate. Furthermore, in this era of biological therapy, PASI 90 may now supersede PASI 75 as the treatment expectation of many patients and clinicians; a 16‐week PASI 90 response rate of 15% in this study compares poorly with those achieved with biologics (range 23–68%) . Biologics may therefore start to appear more cost‐effective, particularly as the main comparator becomes more expensive.…”

“…Participants were methotrexate‐naive adults diagnosed with moderate‐to‐severe chronic plaque psoriasis as defined by Finlay's ‘rule of tens’ [body surface area involved > 10%, Psoriasis Area and Severity Index (PASI) > 10 or Dermatology Life Quality Index score > 10]. Participants were almost exclusively of white ethnic origin (98–100%) and on average had lower PASI scores (mean PASI 15) than seen in most biological trials (weighted average PASI 20·5 from 41 RCTs), suggesting that the results may be more generalizable to those at the moderate, rather than severe, end of this disease severity spectrum. The mean age of participants was the mid‐40s, with mean disease durations of 14 years (placebo–methotrexate group) and 21 years (methotrexate–methotrexate group), representing a population affected by chronic psoriasis for the majority of their adulthood.…”