Victor Llorenç1, Miguel Cordero-Coma2, Ana Blanco-Esteban3, Henar Heras-Mulero4, María-José Losada-Castillo5, Vega Jovani-Casano6, Elia Valls-Pascual7, Margarita Jodar-Marquez8, Ángel García-Aparicio9, Alejandro Fonollosa10, Juan Jacobo González-Guijarro11, Luís Rodriguez-Melian12, Manuel Fernández-Prada13, María Jerez-Fidalgo14, Marisa Hernandez-Garfella15, Cristina Esquinas16, Maite Sainz-de-la-Maza17, Alfredo Adán17. 1. Clínic Institute of Ophthalmology (ICOF), Clínic Hospital of Barcelona, Barcelona, Spain. Electronic address: Llorens.victor@gmail.com. 2. Ophthalmology Department, Hospital de León, León, Spain. 3. Ophthalmology Department, Hospital Universitario de Donostia, San Sebastián, Spain. 4. Ophthalmology Department, Complejo Hospitalario de Navarra, Pamplona, Spain. 5. Ophthalmology Department, Hospital Universitario de Canarias, Tenerife, Spain. 6. Rheumatology Department, Hospital General Universitario de Alicante, Alicante, Spain. 7. Rheumatology Department, Hospital Dr. Peset, Valencia, Spain. 8. Ophthalmology Department, Hospital Regional de Málaga, Málaga, Spain. 9. Rheumatology Department, Hospital Virgen de la Salud, Toledo, Spain. 10. Ophthalmology Department, Hospital de Cruces, Bilbao, Spain. 11. Ophthalmology Department, Hospital Universitario de la Princesa, Madrid, Spain. 12. Ophthalmology Department, Hospital Insular de Gran Canaria, Las Palmas, Spain. 13. Rheumatology Department, Hospital Universitario de Guadalajara, Guadalajara, Spain. 14. Ophthalmology Department, Hospital Perpetuo Socorro, Badajoz, Spain. 15. Ophthalmology Department, Hospital General de Valencia, Valencia, Spain. 16. Vall d'Hebron Research Institute, Autonomous University of Barcelona, Barcelona, Spain. 17. Clínic Institute of Ophthalmology (ICOF), Clínic Hospital of Barcelona, Barcelona, Spain.
Abstract
PURPOSE: To study the drug retention rate (DRR), causes, and predictors of discontinuation of adalimumab (ADA) in a real-world uveitis setting. DESIGN: Multicentric, nationwide, registry-based, ambispective, observational study. PARTICIPANTS: Patients treated with ADA for noninfectious uveitis (NIU) in the Biotherapies for Uveitis (BioÚvea) Spanish registry from November 2016 to November 2017. METHODS: Demographics, clinical data, timing, and reasons for discontinuation, if occurred, were recorded. The 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 (PHM) and propensity score matching were used to identify predictors for discontinuation due to inefficacy and adverse events. MAIN OUTCOME MEASURES: Drug retention rate and DRT. RESULTS: A total of 392 patients were analyzed, including 218 women. Median age was 39 (interquartile range, 25) years. Nonanterior 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. The DRR at 6, 12, 24, and 60 months was 92.97%, 87.68%, 76.31%, and 54.28%, respectively. Adalimumab was discontinued in 151 patients. Discontinuation was due to lack or loss of efficacy in 74 patients, adverse event in 34 patients, and sustained quiescence in 25 patients. Recorded adverse events included infections in 10 patients and malignant neoplasms in 3 patients. Concurrent classic immunomodulatory therapy (IMT) was given to 251 patients. We did not find DRT differences regarding the use of concurrent IMT. Adalimumab was prescribed as a second or greater biotherapy line in 76 patients who showed shorter DRT (P = 0.038). Starting ADA in nonbiotherapy-naive patients was a predictor for "discontinuation due to inefficacy," whereas undifferentiated uveitis was a predictor for "discontinuation due to adverse event." Drug retention time was significantly shorter when spared or intensified, mainly due to discontinuation after sustained quiescence. CONCLUSIONS: Drug retention rate of ADA in uveitis at 60 months was 54.28%, with a good safety profile. The use of concurrent IMT did not show a significant influence on DRT. The use of ADA as a second or further biotherapy could be predictive for discontinuation due to inefficacy. Undifferentiated uveitis may be prone to premature discontinuation of ADA due to adverse events.
PURPOSE: To study the drug retention rate (DRR), causes, and predictors of discontinuation of adalimumab (ADA) in a real-world uveitis setting. DESIGN: Multicentric, nationwide, registry-based, ambispective, observational study. PARTICIPANTS: Patients treated with ADA for noninfectious uveitis (NIU) in the Biotherapies for Uveitis (BioÚvea) Spanish registry from November 2016 to November 2017. METHODS: Demographics, clinical data, timing, and reasons for discontinuation, if occurred, were recorded. The 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 (PHM) and propensity score matching were used to identify predictors for discontinuation due to inefficacy and adverse events. MAIN OUTCOME MEASURES: Drug retention rate and DRT. RESULTS: A total of 392 patients were analyzed, including 218 women. Median age was 39 (interquartile range, 25) years. Nonanterior 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. The DRR at 6, 12, 24, and 60 months was 92.97%, 87.68%, 76.31%, and 54.28%, respectively. Adalimumab was discontinued in 151 patients. Discontinuation was due to lack or loss of efficacy in 74 patients, adverse event in 34 patients, and sustained quiescence in 25 patients. Recorded adverse events included infections in 10 patients and malignant neoplasms in 3 patients. Concurrent classic immunomodulatory therapy (IMT) was given to 251 patients. We did not find DRT differences regarding the use of concurrent IMT. Adalimumab was prescribed as a second or greater biotherapy line in 76 patients who showed shorter DRT (P = 0.038). Starting ADA in nonbiotherapy-naive patients was a predictor for "discontinuation due to inefficacy," whereas undifferentiated uveitis was a predictor for "discontinuation due to adverse event." Drug retention time was significantly shorter when spared or intensified, mainly due to discontinuation after sustained quiescence. CONCLUSIONS: Drug retention rate of ADA in uveitis at 60 months was 54.28%, with a good safety profile. The use of concurrent IMT did not show a significant influence on DRT. The use of ADA as a second or further biotherapy could be predictive for discontinuation due to inefficacy. Undifferentiated uveitis may be prone to premature discontinuation of ADA due to adverse events.
Authors: Ana Belen Rivas; Amanda Lopez-Picado; Valentina Calamia; Ester Carreño; Lidia Cocho; Miguel Cordero-Coma; Alex Fonollosa; Felix M Francisco Hernandez; Angel Garcia-Aparicio; Javier Garcia-Gonzalez; Jose Juan Mondejar; Leticia Lojo-Oliveira; Llucí Martínez-Costa; Santiago Munoz; Diana Peiteado; Jose Antonio Pinto; Beatriz Rodriguez-Lozano; Esperanza Pato; David Diaz-Valle; Elena Molina; Luis Alberto Tebar; Luis Rodriguez-Rodriguez Journal: BMJ Open Date: 2022-03-22 Impact factor: 2.692