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Antibiotic Use and the Persistence of Biologic Therapies in Patients With Psoriasis
Raphaël Ouakrat1,2, Laetitia Penso1, Denis Jullien3
1Epidemiology in Dermatology and Evaluation of Therapeutics, EA7379, Paris-Est University, Université Paris-Est Créteil (UPEC), Créteil, France.
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.
Insights
Antibiotic use increases the risk of discontinuing biologic therapies for psoriasis. This suggests antibiotics may reduce biologic effectiveness, possibly by altering gut bacteria. Further research is needed.
Area of Science:
- Dermatology
- Pharmacology
- Microbiology
Background:
- Biologic therapies are crucial for psoriasis management.
- Long-term effectiveness of biologics can decrease over time.
- Antibiotic-induced gut microbiota changes are a potential cause for reduced biologic persistence.
Purpose of the Study:
- To investigate the association between antibiotic exposure and the persistence of biologic therapies in psoriasis patients.
- To determine if antibiotic use impacts the effectiveness and duration of biologic treatments.
Main Methods:
- Retrospective cohort study using French National Health Insurance data (2011-2022).
- Included adults initiating biologic therapy for psoriasis, excluding those with inflammatory bowel disease.
- Weighted Cox marginal structural models analyzed time-dependent antibiotic exposure and biologic discontinuation.
Main Results:
- 36,129 patients were included; 25.9% had baseline antibiotic exposure, 60.6% during follow-up.
- Antibiotic exposure was linked to a higher risk of biologic discontinuation (aHR, 1.12).
- A dose-response relationship was observed, with multiple dispensations showing a stronger effect (aHR, 1.29).
Conclusions:
- Antibiotic exposure is significantly associated with increased biologic therapy discontinuation in psoriasis.
- Findings support the hypothesis that antibiotics may impair biologic persistence, potentially via gut dysbiosis.
- Unmeasured confounders necessitate further studies for causal interpretation.
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