Long-term drug survival of biological agents in patients with rheumatoid arthritis in clinical practice

Objectives: To assess and compare the long-term drug survival (time to drug discontinuation) of biological agents (BA) in patients with rheumatoid arthritis (RA) in clinical practice. Factors associated with discontinuation of BAs were also investigated. Method: We conducted an observational longitudinal study of RA patients taking BAs from 1999 to 2013. The primary endpoint was BA discontinuation due to: adverse drug reactions (ADRs), inefficacy, and other causes. Incidence rates of discontinuation (IRs) per 100 patient-years were estimated using survival techniques. Comparisons between BA discontinuation rates and other associated factors were made using Cox regression models. Results: We included 851 courses of BA therapy (1869 patient-years). Adalimumab (33%) was the BA most frequently used, followed by etanercept (24.4%), infliximab, and rituximab. Treatment was suspended in 558 cases [IR 29.8, 95% confidence interval (CI) 27-32]. In the first year of therapy 68% continued on BAs, and after 10 years the retention rate did not exceed 10%. The IR due to inefficacy was 12.1 (95% CI 10.6-13.8) and the IR of ADRs was 13.6 (95% CI 12-15). The unadjusted IR was higher for rituximab than for tumour necrosis factor (TNF) antagonists. In multivariate analysis, infliximab was the BA with the highest risk of discontinuation, compared to adalimumab. Calendar period, taking subsequent courses of BAs, concomitant therapy, and specific comorbidities were also independent factors associated with discontinuation. Conclusions: After several years of BA treatment in clinical practice, the survival rate was low, mainly as a result of ADRs and inefficacy. We also found differences between the discontinuation rates of BAs and other clinical factors that modify their survival.