Targeted therapies for patients with moderate-to-severe psoriasis: a systematic review and network meta-analysis of PASI response at 1 year.

PURPOSE: To compare PASI outcomes of approved biologics and apremilast after 1 year of treatment. METHODS: A systematic review identified RCTs and long-term extensions reporting PASI 75, 90, and 100 responses in adults with moderate-to-severe psoriasis. Data for analysis were modeled using a Bayesian multinomial likelihood model with probit link. RESULTS: Twenty-eight studies reporting PASI responses were included in the network meta-analysis. Differences in study design led to a stepwise approach to synthesis, consisting of two analyses. The primary analysis included nine RCTs investigating comparative efficacy at 1 year. Results indicated risankizumab, brodalumab, and guselkumab were the most effective therapies, followed by ixekizumab and secukinumab; all demonstrated superiority to ustekinumab and etanercept. The secondary analysis extended the primary analysis with 19 further studies comparing active interventions to placebo outcomes extrapolated from induction. The interventions generating the highest PASI response were the same as the primary analysis. These therapies were more effective than apremilast, ustekinumab, adalimumab, certolizumab, etanercept, and infliximab. CONCLUSIONS: This NMA demonstrated that evaluated IL-17 and IL-23 inhibitors outperformed other biological therapies after 1 year. Risankizumab had a higher probability of achieving PASI outcomes than all other biologics, except brodalumab and guselkumab, where no significant difference could be concluded.

Assessing the Quality and Coherence of Network Meta-Analyses of Biologics in Plaque Psoriasis: What Does All This Evidence Synthesis Tell Us?

INTRODUCTION: A range of treatments are available for moderate-to-severe psoriasis; however, there remains a paucity of direct comparisons of these in head-to-head trials. Network meta-analyses (NMA) allow comparisons of these to support clinical decision making. This systematic literature review assesses the methodological quality of NMAs available for moderate-to-severe psoriasis and compares their methods and results. Their validity and applicability for current practice is also assessed. METHODS: A systematic review of published NMAs of at least two biologics for moderate-to-severe psoriasis was undertaken. Embase, MEDLINE, MEDLINE In-Process, and the Cochrane Library were last searched on 19 February 2020. The quality of NMAs was assessed using the International Society of Pharmacoeconomics and Outcomes Research (ISPOR) criteria. NMA methodology, funding, and results were compared and differences in results explored. RESULTS: Twenty-five analyses evaluating up to 19 different treatments at 8-24 weeks, and two analyses at 1 year, were included. Psoriasis Area Severity Index (PASI) response was assessed in 23, facilitating comparisons between NMAs. All NMAs met at least half of the ISPOR criteria. The major limitations were explaining the rationale for methodology, exploring effect modifiers, and consistency between direct and indirect estimates. The analyses differed in model type (Bayesian or frequentist), analysis of PASI response (binomial or multinomial), and analysis of different treatment doses (separate or pooled). PASI results were broadly similar, except for the Cochrane Collaboration NMA which provided lower estimates of treatment efficacy versus placebo. This analysis differed methodologically from others, including pooling data for different doses. CONCLUSIONS: Based on PASI 90 at induction, the majority of recent NMAs came to similar conclusions: interleukin (IL) 17 inhibitors (brodalumab, ixekizumab, secukinumab), IL-23 inhibitors (guselkumab and risankizumab) and infliximab were most efficacious, supporting the validity of NMAs in this clinical area. Decisions should be made using high-quality, up-to-date NMAs with assumptions relevant to clinical practice.

Assessing the relative efficacy of interleukin-17 and interleukin-23 targeted treatments for moderate-to-severe plaque psoriasis: A systematic review and network meta-analysis of PASI response.

INTRODUCTION: New generation biologics, including interleukin (IL)-17 and IL-23 inhibitors, have delivered higher rates of skin clearance than older treatments in head-to-head studies. However, studies comparing these new biologics directly to one another are limited. OBJECTIVES: To compare the short-term efficacy of available (or imminently available) biologic and non-biologic systemic therapies for treating patients with moderate-to-severe plaque psoriasis. METHODS: A systematic review was undertaken to identify randomised controlled trials evaluating biologic treatments, apremilast and dimethyl fumarate. MEDLINE, MEDLINE In-Process, Embase and the Cochrane Library were searched from the 1st January 2000 to 22nd November 2018. A Bayesian network meta-analysis (NMA) using a random-effects multinomial likelihood model with probit link and meta-regression to adjust for cross-trial variation in placebo responses compared the efficacy of interventions at inducing different levels of Psoriasis Area and Severity Index (PASI) response during the induction period. A range of sensitivity analyses was undertaken. RESULTS: Seventy-seven trials (34,816 patients) were included in the NMA. The base-case analysis showed that all active treatments were superior to placebo. IL-17 inhibitors, guselkumab and risankizumab were found to be more efficacious than tildrakizumab, ustekinumab, all TNF inhibitors and non-biologic systemic treatments at inducing all levels of PASI response. In addition, brodalumab, ixekizumab and risankizumab were significantly more efficacious than secukinumab; no significant difference was found in the comparison with guselkumab. The greatest benefit of brodalumab, ixekizumab, guselkumab, and risankizumab was seen for PASI 90 and PASI 100 response. Results were consistent across all analyses. CONCLUSIONS: In the NMA brodalumab, ixekizumab, risankizumab and guselkumab showed the highest levels of short-term efficacy. There were differences in efficacy between treatments within the same class. Longer-term analyses are needed to understand differences between these drugs beyond induction in what is a life-long condition.

The comparative efficacy of brodalumab in patients with moderate-to-severe psoriasis: a systematic literature review and network meta-analysis.

PURPOSE: To evaluate the relative efficacy of brodalumab compared with approved biologic therapies and apremilast for moderate-to-severe psoriasis. METHODS: We searched MEDLINE, Embase, and Cochrane for randomized controlled trials reporting induction phase responses. The primary analysis examined the proportion of patients achieving Psoriasis Area Severity Index (PASI) 50, 75, 90, or 100 responses using a random-effects Bayesian multinomial likelihood model with probit link, with and without adjustment for variation in study-level placebo responses. RESULTS: A total of 54 studies were included. Based on PASI 100 response, the most efficacious therapies were brodalumab 210 mg every two weeks (Q2W) and ixekizumab. Brodalumab 210 mg Q2W was significantly more efficacious than adalimumab, apremilast, brodalumab 140 mg Q2W, etanercept, infliximab, secukinumab, and ustekinumab. Results were consistent for PASI 50, 75, and 90 outcomes and all sensitivity analyses. CONCLUSIONS: Our findings are consistent with pivotal trials which indicate that high levels of complete clearance can be achieved with brodalumab. Based on existing evidence, induction-phase efficacy of brodalumab is similar to ixekizumab and superior to other approved therapies, including anti-TNFs, apremilast, secukinumab, and ustekinumab.