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.

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.

Background Patients with moderate‐to‐severe psoriasis require long‐term treatment, yet few trials compare outcomes beyond a short‐term induction period. Quantitative comparisons of long‐term outcomes in patients with psoriasis are limited. To our knowledge, no network meta‐analysis (NMA) of such data has been performed. Objective To compare novel systemic therapies, both biologic and non‐biologic, approved for moderate‐to‐severe psoriasis by conducting a systematic review (SR) and NMA of Psoriasis Area and Severity Index (PASI) outcomes measured at or around 1 year. Methods An SR was conducted to identify studies reporting PASI 75, PASI 90 and PASI 100 responses. Feasibility of an NMA on maintenance phase endpoints was assessed and sources of heterogeneity considered. Data appropriate for analysis were modelled using a Bayesian multinomial likelihood model with probit link. Wherever possible, data corresponding to an intention‐to‐treat approach with non‐responder imputation were used. Results Twenty‐four studies reporting outcomes at 40–64 weeks were identified, but heterogeneity in study design allowed synthesis of only 17. Four 52‐week randomized controlled trials (RCTs) comprised the primary analysis, which found brodalumab was significantly more efficacious than secukinumab, ustekinumab and etanercept. Secukinumab was also more efficacious than ustekinumab and both outperformed etanercept. In a secondary analysis, evidence from 13 additional studies and 4 further therapies (adalimumab, apremilast, infliximab and ixekizumab) was included by comparing long‐term outcomes from active interventions to placebo outcomes extrapolated from induction. Results were consistent with the primary analysis: brodalumab was most effective, followed by ixekizumab and secukinumab, then ustekinumab, infliximab and adalimumab. Etanercept and apremilast had the lowest expected long‐term efficacy. Results were similar when studies with low prior exposure to biological therapies were excluded. Conclusion Results suggest that brodalumab is associated with a higher likelihood of sustained PASI response, including complete clearance, at week 52 than comparators. Further long‐term active‐comparator RCT data are required to better assess relative efficacy across therapies.

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Insertable cardiac monitors are a cost-effective diagnostic tool for the prevention of recurrent stroke in patients with cryptogenic stroke. The cost-effectiveness results have relevance for the UK and across value-based healthcare systems that assess costs relative to outcomes.

SummaryThe majority of people with psoriasis have localized disease, where topical therapy forms the cornerstone of treatment. We set out to summarize evidence on the relative efficacy, safety and tolerability of different topical treatments used in plaque psoriasis. We undertook a systematic review and meta-analyses of randomized trial data of U.K.-licensed topical therapies. The primary outcome was clear or nearly clear status stratified for (i) trunk and limbs; and (ii) scalp. Network meta-analyses allowed ranking of treatment efficacy. In total, 48 studies were available for trunk and limb psoriasis, and 17 for scalp psoriasis (22 028 patients in total); the majority included people with at least moderate severity psoriasis. Strategies containing potent corticosteroids (alone or in combination with a vitamin D analogue) or very potent corticosteroids dominated the treatment hierarchy at both sites (trunk and limbs, scalp); coal tar and retinoids were no better than placebo. No significant differences in achievement of clear or nearly clear status were observed between twice-and once-daily application of the same intervention or between any of the following: combined vitamin D analogue and potent corticosteroid (applied separately or in a single product), very potent corticosteroids, or potent corticosteroids (applied twice daily). Investigator and patient assessment of response differed significantly for some interventions (response rates to very potent corticosteroids: 78% and 39%, respectively). No significant differences were noted for tolerability or steroid atrophy, but data were limited. In conclusion, corticosteroids are highly effective in psoriasis when used continuously for up to 8 weeks and intermittently for up to 52 weeks. Coal tar and retinoids are of limited benefit. There is a lack of long-term efficacy and safety data available on topical interventions used for psoriasis.Psoriasis is a common chronic inflammatory skin condition and, although generally not life threatening, it can have a profound impact on physical, psychological and social wellbeing. 1 While recent advances and investment in high-cost biological therapies have revolutionized outcomes for people with severe disease, comparatively little attention has been paid to topical therapy, which forms the cornerstone of management for the majority of people with psoriasis. 2 Furthermore, the degree of disability does not necessarily correlate with objective measures of disease extent or severity, 3 and people with minimal involvement (less than the equivalent of three palm areas) state that psoriasis has a major effect on their life, 4 underscoring the importance of effective treatment in this group.Corticosteroids, vitamin D 3 and its analogues, calcineurin inhibitors, retinoids, tar, dithranol and keratolytic agents such as salicylic acid and urea are all used, 5 and come in a vast array of formulations, combinations and potencies. Choice of treatment is tailored to the needs of the patient and includes consideration of the nature of...

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.