Systematic review and mixed treatment comparison of biologic therapies in psoriasis Porównawcza ocena skuteczno ci klinicznej leków biologicznych stosowanych w leczeniu uszczycy: przegl d systematyczny i metaanaliza sieciowa

Background: Introduction of biological agents has significantly improved the long-term management of moderate to severe plaque psoriasis. In the absence of head-to-head randomized controlled trials (RCT) comparing directly all available biological treatments, relative effectiveness of competing interventions can only be estimated by means of indirect comparison methods. Objectives: To evaluate the clinical effectiveness of biologic agents approved for treating adult patients with chronic plaque psoriasis in Poland through a systematic literature review and mixed treatment comparison (MTC) analysis. Methods: A systematic review was conducted to identify all relevant RCTs evaluating the efficacy of biologic treatments of moderate-to-severe psoriasis – infliximab, etanercept (with two dosing regimens: 25 or 50 mg), adalimumab and ustekinumab, in terms of PASI 50/75/90 response at 10-16 week. A network meta-analysis was conducted based on the ordered probit model developed by the York Assessment Group. Base-case analysis was supplemented with an additional analysis using standard MTC model for binary data (PASI 75) on a logit scale. Sensitivity analyses were also performed. Results: 17 RCTs were included in the MTC analysis of which 16 compared a biologic treatment with placebo and one RCT compared two biologic agents. All biologic therapies were more efficacious than placebo in terms of PASI 75 response, with a relative benefit (RB) of 19.58 (95% CI: 16.45, 23.07) for infliximab, 17.53 (95% CI: 14.78 , 20.67) for ustekinumab, 14.41 (95% CI: 11.65, 17.29) for adalimumab, 12.71 (95% CI: 10.42, 15.23) for etanercept 50 mg and 9.55 (95% CI: 7.36, 11.97) for etanercept 25 mg. The highest probability of PASI 75 response is achieved with infliximab (82%). Next ranked strategies in terms of effectiveness are: ustekinumab (73%), adalimumab (60%), etanercept 50 mg (53%), etanercept 25 mg (40%) and supportive care/placebo (4%). Bayesian posterior probability of infliximab being the most effective option is 94%. Ustekinumab is most effective option with 6% probability and other biologics with probability <1%. The rank order of biologic treatments in efficacy remained unchanged in all sensitivity analysis scenarios. Conclusions: Biological agents are highly effective in terms of PASI response at 10-16 weeks. MTC, representing a synthesis of all available evidence from RCTs, provides valuable information on the relative effectiveness of biological drugs in the dearth of head-to-head trials.