Risk of candidiasis associated with interleukin-17 inhibitors: A real-world observational study of multiple independent sources.
retrospective_cohort · Level III
Where this comes from
- Record sourced from PubMed, PMID 34950923.
- Also identified by DOI 10.1016/j.lanepe.2021.100266 and PMC identifier 8671639.
- Licence recorded as CC BY-NC-ND.
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Abstract
Biologics directed against the T-helper (Th)-17 pathway have been approved for several inflammatory diseases. Interleukin (IL)-17 is involved in anti- <i><b>Candida</b></i> host defense, and clinical trials suggested increased candidiasis incidence during IL-17 inhibitor therapy. We describe the worldwide epidemiology of candidiasis during Th17 inhibitor therapy, and immunological mechanisms involved in candidiasis susceptibility. A comprehensive analysis of multiple independent sources reporting <i><b>Candida</b></i> adverse events during biologics inhibiting the Th17 pathway was performed. Association between Th17 inhibitors and candidiasis was assessed using safety reports of (1) WHO and (2) EMA, (3) a population-based prescriptions registry, and (4) a psoriasis cohort. In a cohort of psoriasis patients experiencing candidiasis during Th17 inhibitors, <i><b>Candida</b></i> killing by immune cells and serum inflammatory proteome were analyzed. A strong association between IL-17 inhibitors and candidiasis (ROR 10·20) was found in the WHO database, particularly for cutaneous (ROR 12·28), oropharyngeal (ROR 19·18), and esophageal candidiasis (ROR 21·20). Risk was higher relative to TNF-α inhibitors (4-10-fold, depending on candidiasis type), confirmed by EMA reports (16-33-fold), prescriptions registry (2-42-fold), and a psoriasis cohort (3-25-fold). After start of IL-17 inhibitors, patients' risk of candidiasis requiring antifungals increased 2-16 fold. In the psoriasis cohort, 58% of IL-17 treatment episodes were associated with candidiasis. In Th17 inhibitor recipients, proteins involved in anti- <i><b>Candida</b></i> immunity and <i><b>Candida</b></i> killing by mononuclear leukocytes were impaired. IL-17 inhibitors are associated with an increased risk of oropharyngeal, esophageal, and cutaneous candidiasis, posing a significant disease burden for IL-17 inhibitor recipients. RadboudUMC.