Safety of biological disease-modifying antirheumatic drugs in rheumatoid arthritis

Objective: The aim of this study was to assess the safety of the most frequently used biologic disease-modifying antirheumatic drugs in rheumatoid arthritis patients in clinical practice. Method: A retrospective longitudinal observational study was performed. Clinical information was obtained from the electronic health records of patients diagnosed and treated for rheumatoid arthritis, who had received at least one biologic disease-modifying antirheumatic drug dispensed between 2001 and 2013 from a third- level Hospital pharmacy. Adverse reactions during biologic disease-modifying antirheumatic drugs treatments were analysed, as well as the reasons for treatment discontinuation. A disproportionality analysis (odds ratio with 95% confidence interval) was performed to compare adverse drug reactions related to different system organ classes, the period between the drug start date and the reaction start date (latency period), and previous knowledge of the adverse reactions. Results: In total, 210 patients were included in the analysis (73% women, median age 47 years), with 399 prescriptions for biologic diseas-emodifying antirheumatic drugs and 1,515 adverse reactions potentially related to them. The increased frequency of adverse reactions for each system organ class related to each biologic disease-modifying antirheumatic drug was as follows: general disorders and administration site disturbances with infliximab (2.3 [1.3-4.0]), infections (1.6 [1.3-2.1]) and immune system reactions with etanercept (4.2 [1.2-14.6]), hepatobiliary disorders with adalimumab (2.1 [1.2-3.6]), ophthalmic adverse reactions (1.9 [1.2-3.1]) and cardiac disorders (2.9 [1.0-8.4]) with rituximab, and blood and lymphatic system disorders with tocilizumab (2.9 [1.8- 4.7]) and abatacept (3.0 [1.6-5.8)]. The mean latency period was 5 to 33 months. Most adverse reactions were related to adalimumab (93.6%; P < 0.01), whereas the fewest adverse reactions were related to tocilizumab (55.2%; P < 0.01). Most treatment withdrawals related to adverse reactions were identified during the first year of biologic disease-modifying antirheumatic drugs treatment. Conclusions: Tumour necrosis factor a inhibitors were associated with general disorders and administration site disturbances, infections and immune system reactions, and hepatobiliary abormalities, whereas nontumour necrosis factor a inhibitors were associated with cardiac disorders as well as blood and lymphatic system disorders. Treatment withdrawals mainly occurred during the first year of treatment. Most of the adverse reactions have been previously described.