Meta-analysis results do not reflect the real safety of biologics in psoriasis.

BACKGROUND: In reported systematic reviews and meta-analyses of randomized controlled trials (RCTs) assessing treatments for psoriasis, the proportion of serious adverse events (SAEs) did not differ between treatments and placebo. Including cases of psoriasis worsening as SAEs may explain the lack of difference. OBJECTIVES: This systematic review and meta-analysis aimed to explore this possibility. METHODS: Among the 140 RCTs included in the Living Network Cochrane Review (last search on 8 May 2019), we selected those comparing a biologic treatment against placebo. The primary outcome was the numbers of SAEs in the treatment and placebo arms after excluding cases of psoriasis worsening. Secondary outcomes were the number of adverse events (AEs) of special interest. The trial was registered on PROSPERO (CRD42019124495). RESULTS: We analysed 51 RCTs. Of these, 21 included at least one anti-tumour necrosis factor (TNF)-α arm, 15 one anti-interleukin (IL)-17 arm, 11 one anti-IL-23 arm and nine one anti-IL-12/23 arm. With cases of psoriasis worsening included, the risk of occurrence of SAEs between biologic treatments and placebo did not differ: risk ratio (RR) 1·09, 95% confidence interval (CI) 0·88-1·36. After excluding cases of psoriasis worsening, the RR became significant (RR 1·30, 95% CI 1·02-1·65). By drug class, the RRs were for anti-TNF-α, 1·68 (95% CI 1·11-2·54; no missing data); anti-IL-17, 1·28 (95% CI 0·88-1·85; no missing data); anti-IL-23, 0·95 (95% CI 0·59-1·52; no missing data) and anti-IL-12/23, 1·18 (95% CI 0·72-1·94; no missing data). We were unable to examine potential differences in AEs of special interest between biologic treatments and placebo arms because of the small number of events. CONCLUSIONS: On excluding cases of worsening psoriasis, the risk of occurrence of SAEs is higher in the biologic than in the placebo arm. Given the rare events, we could not highlight whether this higher risk of SAEs was related to AEs of special interest. Reporting of SAEs in clinical trials has to be changed to provide more transparency through the separate reporting of disease flares leading to hospital admission and other SAEs.

Surgical treatment for hydrosalpinx prior to in-vitro fertilization embryo transfer: a network meta-analysis.

OBJECTIVE: The presence of hydrosalpinx impairs the outcome of in-vitro fertilization embryo transfer (IVF-ET). Surgical methods to either aspirate the fluid or isolate the affected Fallopian tubes have been attempted as a means of improving outcome. The aim of this network meta-analysis was to compare the effectiveness of surgical treatments for hydrosalpinx before IVF-ET. METHODS: An electronic search of MEDLINE, Scopus, Cochrane Central Register of Controlled Trials (Central) and the US Registry of clinical trials for articles published from inception to July 2015 was performed. Eligibility criteria included randomized controlled trials of women with hydrosalpinx before IVF-ET comparing ultrasound-guided aspiration of the fluid, tubal occlusion, salpingectomy or no intervention. Ongoing pregnancy was the primary outcome and clinical pregnancy, ectopic pregnancy and miscarriage were secondary outcomes. A random-effects network meta-analysis synthesizing direct and indirect evidence from the included trials was carried out. We estimated the relative effect sizes as risk ratios (RRs) and obtained the relative ranking of the interventions using cumulative ranking curves. The quality of evidence according to GRADE guidelines, adapted for network meta-analysis, was assessed. RESULTS: Proximal tubal occlusion (RR, 3.22 (95% CI, 1.27-8.14)) and salpingectomy (RR, 2.24 (95% CI, 1.27-3.95)) for treatment of hydrosalpinx were superior to no intervention for ongoing pregnancy. For an outcome of clinical pregnancy, all three interventions appeared to be superior to no intervention. No superiority could be ascertained between the three surgical methods for any of the outcomes. In terms of relative ranking, tubal occlusion was the best surgical treatment followed by salpingectomy for ongoing and clinical pregnancy rates. No significant statistical inconsistency was detected; however, the point estimates for some inconsistency factors and their CIs were relatively large. The small study number and sizes were the main limitations. The quality of evidence was commonly low/very low, especially when aspiration was involved, indicating that the results were not conclusive and should be interpreted with caution. CONCLUSIONS: Proximal tubal occlusion, salpingectomy and aspiration for treatment of hydrosalpinx scored consistently better than did no intervention for the outcome of IVF-ET. In terms of relative ranking, proximal tubal occlusion appeared to be the most effective intervention, followed by salpingectomy. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.