Risk of Candida Infection and Serious Infections in Patients with Moderate-to-Severe Psoriasis Receiving Biologics: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

BACKGROUND: Biological agents used to treat moderate-to-severe plaque psoriasis have been associated with Candida infection and other serious infections. It is, however, necessary to verify whether biologic agents increase the risk of Candida infection and serious infections and whether these risks vary among biologics. METHODS: PubMed, EMBASE, and Cochrane Library were searched for eligible randomized controlled trials (RCTs) from their inception to December 2021. Results from individual RCT were pooled using Peto's method with a fixed-effects model, and I(2) was calculated to assess the heterogeneity. A Cochrane collaboration tool was used to examine bias risk, and Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) were used to assess the quality of evidence. RESULTS: This study included 48 published articles with data from 52 RCTs involving 27297 participants. The anti-interleukin (IL)-17 agents (95% confidence interval (CI) = 1.54–3.45, P < 0.0001) and anti-IL-12/23 agents (95% CI = 1.69–3.83, P < 0.0001) were associated with an increased risk of Candida infection compared with placebos, but there was no difference in Candida infection risk between anti-IL-17 agents and tumor necrosis factor inhibitors (TNFi) (95% CI = 0.92–3.07, P=0.09). There was no evidence that the biological agents increased the risk of serious infections in adult psoriasis (95% CI = 0.93–2.06, P=0.11) or that the biologics differed in the risk of serious infections. CONCLUSIONS: Our results indicated that anti-IL-17 agents, especially secukinumab, were associated with the increased risk of Candida infection. The clinically used biological agents did not increase the risk of serious infections.