In systematic reviews (SR) and meta-analyses (MA) of randomized controlled trials (RCTs) assessing treatments of 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. This SR and MA aimed to explore this possibility.Among the 140 RCTs included in the Living Network Cochrane Review (last search on May 8, 2019), we selected those comparing a biological treatment to placebo. The primary outcome was the number of SAEs in treatment and placebo arms after excluding cases of psoriasis worsening. Secondary outcomes were number of adverse events (AEs) of special interest.We analyzed 51 RCTs. Of these, 21 included at least one anti-TNF-alpha arm, 15 one anti-IL-17 arm, 11 one anti-IL-23 arm and 9 one anti-IL-12/23 arm. With cases of psoriasis worsening included, the risk of occurrence of SAEs between biological treatments and placebo did not differ: RR=1.09 (95% 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 for anti-TNF-alpha were 1.68 (95% CI 1.11-2.54; 20 out of 21 trials used), 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 the AEs of special interest between biologic treatments and placebo arms because of the small number of events.On excluding cases of worsening psoriasis, the risk of occurrence of SAEs is higher in the biological 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.