Incidence of histoplasmosis in patients receiving TNF-alpha inhibitors: A systematic review and meta-analysis

Background: Immunobiological drugs such as TNF-alpha inhibitors are valuable in rescue therapy for autoimmune diseases such as rheumatoid arthritis and inflammatory bowel disease (IBD), but they increase the risk of infectious complications. Histoplasmosis is a significant concern in patients living in endemic regions, however, few studies have assessed the incidence of Histoplasma infection during therapy, and classic estimates may underestimate the risk. This study aimed to produce an updated risk estimate of histoplasmosis in patients on TNF-alpha blocking therapy.Methods: This is a systematic review and meta-analysis of studies that contain parameters for calculating the risk of histoplasmosis in people who use TNF-alpha inhibitors, to produce a risk estimate.Results: We identified 11 studies with the necessary parameters for inclusion in the meta-analysis, most of which were from North America. The incidence rate of histoplasmosis found was 33.52 cases per 100,000 patients treated with TNF-alpha inhibitors (95% CI 12.28-91.46). Considering only studies evaluating monoclonal antibodies, the calculated incidence was 54.88/100,000 patients treated (95%CI 23.45-128.34). In subgroup analysis, the incidence was much higher in patients with IBD compared to rheumatic diseases. There was significant heterogeneity among the studies.Conclusion: The risk of histoplasmosis during TNF-alpha inhibitory therapy may be considerably higher than that found in classical estimates, especially in patients with IBD. There is a lack of studies evaluating histoplasmosis in large endemic areas, such as Central and South America.