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.

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. Electronic supplementary material The online version of this article (10.1007/s13555-020-00463-y) contains supplementary material, which is available to authorized users.

The purpose of this manuscript was to illustrate the impact of the place in the treatment sequence on the cost and cost-effectiveness of different biologics for patients with moderate-to-severe plaque psoriasis. Materials and MethodsWe developed a treatment sequence model and focused on seven different biological treatment options and 840 combinations of treatment sequences. The model converted cost of treatment to a cost per responder by dividing treatment cost by expected number of patients achieving PASI100 after 52 weeks of treatment. We used Spanish ex-factory price levels, dosing recommendations and real-world data on drug survival to calculate the treatment costs. ResultsThe most cost-effective treatment sequence was brodalumab-risankizumab-guselkumabixekizumab, with a cost per responder of €139,281 during the first five years of treatment. In comparison, if brodalumab was not recommended as first-line therapy, total costs would increase by 7.4% to €149,616. If brodalumab was not recommended as any of the first four lines of treatment, total costs would increase by 13.1% to €157,527 relative to the most cost-effective treatment sequence. Conclusions.A sequential therapy model may improve efficiency in the treatment of psoriasis. According to our A c c e p t e d M a n u s c r i p t results, brodalumab as the first-line therapy in Spain leads to the most cost-effective treatment sequence.

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practice. All HTA bodies recommended the three biologic therapies for use in patients with moderate to severe plaque psoriasis who have failed to respond to standard systemic therapies with discontinuation rules if no response was observed after 12-16 (16-20: ixekizumab (SMC)) weeks. Conclusions: The evidence base, and HTA agency decisions, for guselkumab, ixekizumab, and brodalumab submissions were principally aligned. As more biologics are being approved, understanding the requirements of HTA, and undertaking holistic evidence generation, will play a crucial role in enabling access to the novel biologics.