Anti-Interleukin-23 Treatment Linked to Improved Clostridioides difficile Infection Survival

Abstract

Clostridioides difficile is a leading cause of healthcare associated infection and an unacceptably high proportion of patients with C. difficile infection die despite conventional antibiotic treatment. Host-directed immunotherapy has been proposed as an ideal treatment modality for C. difficile infection to mitigate the underlying toxin-mediated pathogenic immune response while sparing protective gut microbes. Interleukin-23 monoclonal antibody inhibitors are used extensively to control pro-inflammatory Th17 immune pathways in psoriasis and inflammatory bowel disease that are similarly important during C. difficile infection. We used a large retrospective electronic health record database to test the hypothesis that hospitalized patients with C. difficile infection who are on anti-IL-23 treatment will have improved survival compared to patients without anti-IL-23. 9,301 anti-IL-23 patients had significantly lower probability of all-cause death within 30 days (0.54%) compared with 1:1 propensity-matched control patients (3.1%). IL-23 inhibition is a promising adjunct to C. difficile treatment and further clinical trials repositioning anti-IL-23 monoclonal antibodies from psoriasis and inflammatory bowel disease to C. difficile infection are warranted.