Drug Retention Rate and Causes of Discontinuation of Adalimumab in Uveitis. Real-World Data from the Biotherapies in Uveitis (BioÚvea) Study Group

Abstract Purpose To study drug retention rate (DRR), causes and predictors of discontinuation of adalimumab (ADA) in real-world uveitis setting. Design Multicentric, nation-wide, registry-based, ambispective, observational study. Subjects Patients treated with ADA for non-infectious uveitis in the Biotherapies for Uveitis (BioUvea) Spanish registry from Nov 2016 to Nov 2017. Methods Demographics, clinical data, timing and reasons for discontinuation, if occurred, were recorded. DRR and drug retention time (DRT) were estimated using the Kaplan-Meier method. Median follow-up was analyzed by reverse Kaplan-Meier. Log-rank test was used for comparisons. Cox proportional hazards model and propensity score matching were used to identify predictors for discontinuation due to inefficacy and adverse events. Main Outcome Measures DRR and DRT. Results 392 patients were analyzed, including 218 females. Median age was 39 (IQR 25) years. Non-anterior uveitis was recorded in 242 patients. Median follow-up was 49.07 (0.97-131.67) months, median DRT (survival) was 69.3 months, and 14 patients were lost to follow-up. DRR at 6, 12, 24 and 60 months was 92.97%, 87.68%, 76.31% and 54.28%, respectively. ADA was discontinued in 151 patients. Discontinuation was due to lack or loss of efficacy in 74, adverse event in 34, and sustained quiescence in 25 patients. Recorded adverse events included: infections in 10 patients and malignant neoplasms in 3. Concurrent classic immunomodulatory therapy (IMT) was given to 251 patients. We did not find DRT differences regarding the use of concurrent IMT. ADA was prescribed as a ≥2nd biotherapy line in 76 patients, who showed shorter DRT (p=0.038). Starting ADA in non-biotherapy-naive patients was a predictor for “discontinuation due to inefficacy”, whereas undifferentiated uveitis was a predictor for “discontinuation due to adverse event”. DRT was significantly shorter when spared or intensified, mainly due to discontinuation after sustained quiescence. Conclusions DRR of ADA in uveitis at 60 months was 54.28%, with a good safety profile. The use of concurrent IMT did not show significant influence on DRT. The use of ADA as a second or more biotherapy could be predictive for discontinuation due to inefficacy. Undifferentiated uveitis may be prone to premature discontinuation of ADA due to adverse events.