Trajectories of use of biologic disease modifying antirheumatic drugs in rheumatoid arthritis: A cohort study of Tuscan patients, Italy

Background: Adherence to biologic Disease Modifying Anti-rheumatic Drugs (bDMARDs) in rheumatoid arthritis (RA) patients is poorly reported, and its interpretation is complex due to recommended discontinuation of the drugs when remission of symptoms is achieved. Objectives: To identify and characterize trajectories of bDMARDs in RA patients. Methods: This is a population based retrospective cohort study using data collected in administrative healthcare databases of Tuscany, an Italian region. We included patients with a first dispensation of bDMARD (infliximab, adalimumab, certolizumab, etanercept, golimumab, abatacept, tocilizumab) from 2010 to 2015 (index date, ID); at least 1 year (y) of look-back period at ID; a RA diagnosis or a rheumatologic visit within 1y after ID; at least 3 dispensations of bDMARD. We excluded patients with dispensations of antineoplastic drugs or cancer diagnosis at baseline, or less than 3y of follow-up.We censored for cancer or pregnancy. We estimated adherence to bDMARD every three months through the Proportion of Day Covered and clustered longitudinal trajectories of adherence in groups. We described the clusters and compared baseline characteristics of patients across clusters. Results: Out of 3,468 first bDMARD users with a RA diagnosis or visit and no history of cancer, 292 (8.4%) had less than 3 dispensations and 79 (2.3%) had less than 3y of follow-up. In the cohort of 3,097 patients, 67.2% were female. The mean age was 52.90 (SD 16.6). The index bDMARDs (ibD) were etanercept (1184 patients, 38.2%), adalimumab (998, 32.2%), infliximab (259, 8.4%), golimumab (234, 7.6%), abatacept (159, 5.1%), certolizumab (149, 4.8%), tocilizumab (114, 3.7%). We identified 3 clusters: in the 1st, including 1,213 patients, adherence was high for 2y, followed by a slow decrease; in the 2nd, 1,744 patients, adherence showed a steady state with moderate decrease over time; in the 3rd, 135 patients, adherence fell abruptly after 9 months. Gender and age did not predict cluster membership. History of fractures and number of specialist visits predicted the 2nd and the 3rd trajectory, respectively. The most common ibD were etanercept (35.7%), adalimumab (32.8%) and golimumab (10.1%) in the 1st group; etanercept (40.3%), adalimumab (32.5%) and infliximab (9.1%) in the 2nd; etanercept (34.8%), adalimumab (23.0%) and abatacept (13.3%) in the 3rd. Conclusions: Three trajectories of adherence were identified: late decrease, slow and steady decrease, early and sudden decrease. Specialist visits, fractures, and ibD were predictive of the cluster membership