Our review shows that compared to placebo, the biologics ixekizumab, secukinumab, brodalumab, guselkumab, certolizumab, and ustekinumab are the best choices for achieving PASI 90 in people with moderate to severe psoriasis on the basis of moderate- to high-certainty evidence. At class level, the biologic treatments anti-IL17, anti-IL12/23, anti-IL23, and anti-TNF alpha were significantly more effective than the small molecules and the conventional systemic agents, too. This NMA evidence is limited to induction therapy (outcomes were measured between 12 to 16 weeks after randomisation) and is not sufficiently relevant for a chronic disease. Moreover, low numbers of studies were found for some of the interventions, and the young age (mean age of 44 years) and high level of disease severity (PASI 20 at baseline) may not be typical of patients seen in daily clinical practice.Another major concern is that short-term trials provide scanty and sometimes poorly reported safety data and thus do not provide useful evidence to create a reliable risk profile of treatments. Indeed, we found no significant difference in the assessed interventions and placebo in terms of SAEs. Methotrexate appeared to have the best safety profile, but as the evidence was of very low to moderate quality, we cannot be sure of the ranking. In order to provide long-term information on the safety of the treatments included in this review, it will be necessary to evaluate non-randomised studies and postmarketing reports released from regulatory agencies as well.In terms of future research, randomised trials comparing directly active agents are necessary once high-quality evidence of benefit against placebo is established, including head-to-head trials amongst and between conventional systemic and small molecules, and between biological agents (anti-IL17 versus anti-IL23, anti-IL23 versus anti-IL12/23, anti-TNF alpha versus anti-IL12/23). Future trials should also undertake systematic subgroup analyses (e.g. assessing biological-naïve patients, baseline psoriasis severity, presence of psoriatic arthritis, etc.). Finally, outcome measure harmonisation is needed in psoriasis trials, and researchers should look at the medium- and long-term benefit and safety of the interventions and the comparative safety of different agents.

Interventions for chronic palmoplantar pustulosis (Review)

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Summary Background Palmoplantar pustulosis (PPP) is a chronic inflammatory disease in which sterile and relapsing pustules appear on the palms and soles. Objectives To assess the effects of interventions for chronic PPP to induce and maintain complete remission. Methods We searched for randomized controlled trials (RCTs), including people with PPP or chronic palmoplantar pustular psoriasis, in the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, LILACS and eight trials registers up to July 2020. Study selection, data extraction and risk‐of‐bias assessment were carried out independently by two review authors. Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) method. Results We included 37 RCTs (1663 participants, 76% women, mean age 50 years). Mean treatment duration was 11 weeks. Topical vitamin D derivative may be more effective than placebo in achieving clearance [risk ratio (RR) 7·83, 95% confidence interval (CI) 1·85–33·12; low‐certainty evidence from two trials]. Concerning biological therapies, there was little or no difference between etanercept and placebo in achieving clearance (low‐certainty evidence from one trial), ustekinumab is less effective than placebo in reducing severity (low‐certainty evidence from one trial), and guselkumab (RR 2·88, 95% CI 1·24–6·69) and secukinumab (RR 1·55, 95% CI 1·02–2·35) are probably better in reducing disease severity (moderate‐certainty evidence from two and one trial(s), respectively) but may cause more serious adverse events than placebo. Conclusions Evidence is lacking for or against major chronic PPP treatments. Risk of bias and imprecision limit our confidence in the results.

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