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

Abstract

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 I2 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.

New biologic (Ab-IPL-IL-17) for IL-17-mediated diseases: identification of the bioactive sequence (nIL-17) for IL-17A/F function

“…Increased intestinal inflammation has been reported in patients with IBD treated with secukinumab or brodalumab, thus increasing disease severity 41. Similarly, various IL-17 biologics have been associated with increased numbers of Candida or upper respiratory tract infections in numerous different patient groups, further increasing patient morbidity 40 42. Psoriasis patients treated with brodalumab have experienced depression/anxiety linked with suicidal thoughts 43.…”

Interleukin inhibitors and the associated risk of candidiasis

“…For instance, risankizumab, a selective anti-IL-23 antibody approved for the treatment of psoriasis, has been observed to induce mucocutaneous candidiasis in approximately 3.4% of cases ( 15 ). This interaction between candidiasis and IL inhibitors is a serious concern for patients undergoing treatment with such inhibitors ( 16 ).…”

Risk of candidiasis associated with interleukin-17 inhibitors: Implications and management

“…This is because these medications suppress the immune response, which is essential in fighting candidiasis (Davidson et al 2022 ). In a randomised, controlled trial of psoriasis patients treated with secukinumab (an IL-17 inhibitor), the incidence of oral candidiasis was higher in the secukinumab group compared to the placebo group (Feng et al 2022 ). Another research on individuals with rheumatoid arthritis receiving ixekizumab, another IL-17 inhibitor, revealed that the incidence of candidiasis was more significant in the ixekizumab group than in the placebo group (Ruggiero et al 2022 ).…”