Abstract
IMPORTANCE: The long-term effectiveness of biologic therapies in psoriasis may decline over time. Gut microbiota alterations induced by antibiotics have been proposed as a potential mechanism impairing biologic persistence. OBJECTIVE: To evaluate the association between antibiotic exposure and the persistence of biologic therapies in patients with psoriasis. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used data from the French National Health Insurance database between June 2011 and December 2022. Adults initiating a biologic therapy for psoriasis were included, excluding those with preexisting inflammatory bowel disease at baseline. Data were analyzed from January to September 2024. EXPOSURES: At baseline, antibiotics exposure was classified as none, 1, or 2 or more dispensations in the 6 months preceding the index date. During follow-up, time-dependent antibiotics exposure was defined as none, 1, or 2 or more antibiotics dispensations in the 6 months prior to each time of follow-up. MAIN OUTCOMES AND MEASURES: The primary outcome was discontinuation or switch of the initial biologic therapy. Exposure to antibiotics was assessed within 6 months prior to biologic initiation and during follow-up. A weighted Cox marginal structural model was used to estimate adjusted hazard ratios. RESULTS: Of 36 129 included patients, 11 228 (42.0%) were female, 20 192 (55.9%) were male, and the mean (SD) age was 48.4 (15.1) years. A total of 9366 (25.9%) were exposed to antibiotics at baseline and 21 900 (60.6%) during follow-up. The most commonly prescribed antibiotic classes were β-lactams, macrolides, and fluoroquinolones. Antibiotic exposure was associated with a higher risk of biologic discontinuation (weighted hazard ratio, 1.12; 95% CI, 1.08-1.16), with a stronger effect observed for multiple dispensations (weighted hazard ratio, 1.29; 95% CI, 1.24-1.35), suggesting a dose-response relationship. CONCLUSIONS AND RELEVANCE: In this cohort study, antibiotic exposure was significantly associated with an increased risk of discontinuation of biologic therapies in psoriasis. These findings support the hypothesis that antibiotics, potentially through gut dysbiosis, may reduce biologic persistence. However, unmeasured confounders limit causal interpretation. Further studies are necessary to validate these findings.