Meta‐analysis results do not reflect the real safety of biologics in psoriasis*

Abstract

Summary 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.

First-Line Biologic Therapy and Obesity in Moderate-to-Severe Psoriasis: Results from the Prospective Multicenter Cohort Psobioteq

“…In addition, obesity data pooled for biologic discontinuation due to adverse events showed statistically significant higher rates in the ETA-alone group. However, in this study, the nature of adverse events was not described and could not be associated with a potential adverse event of special interest, as reported recently [47]. However, our study did not highlight an increased rate of adverse events with biologic therapy for obese versus non-obese groups.…”

Vibration of effect in more than 16 000 pooled analyses of individual participant data from 12 randomised controlled trials comparing canagliflozin and placebo for type 2 diabetes mellitus: multiverse analysis

“…This approach, excluding the beneficial effects of a treatment from the composite of serious adverse events, has been proposed in the field of psoriasis research. 35 Results on serious adverse events were robust in this post hoc sensitivity analysis.…”

Psoriasis-related treatment exposure and hospitalization or in-hospital mortality due to COVID-19 during the first and second wave of the pandemic: cohort study of 1 326 312 patients in France

“…Nonbiologic therapies, target therapies or biologics are used to manage moderate‐to‐severe psoriasis 7 . Post‐marketing studies have allowed for better understanding of their safety profile, demonstrating a favourable risk–benefit ratio despite increased risk of infection 8 . In the current pandemic context, few data have been published on the course of COVID‐19 in patients with psoriasis receiving biologic therapy 9–17 .…”

“…7 Post-marketing studies have allowed for better understanding of their safety profile, demonstrating a favourable risk-benefit ratio despite increased risk of infection. 8 In the current pandemic context, few data have been published on the course of COVID-19 in patients with psoriasis receiving biologic therapy. [9][10][11][12][13][14][15][16][17] All experts agree that in the absence of infection, discontinuing biologic therapy is not recommended, 18,19 a resurgence of the underlying pathology being potentially more deleterious than COVID-19.…”