Longitudinal adherence trajectories to biologic disease modifying anti-rheumatic drugs in Tuscany, Italy

Background: Adherence to biologic disease-modifying anti-rheumatic drugs (bDMARDs) is essential to control rheumatoid arthritis (RA). Compared to traditional approaches, longitudinal adherence trajectories can provide important information to improve treatments efficiency. Objectives: One of the aims of the PATHFINDER study, is to identify longitudinal adherence trajectories to bDMARDs in Tuscan RA patients. Methods: A retrospective drug utilization study was carried out on data collected in the Tuscan administrative databases. We included patients matching the following criteria: the first bDMARD dispensation between 2010 and 2015 (index date); RA diagnosis 5 years before or 1 year after the index date, or RA visit within one year before and after. Patients were followed for 3 years or until death. Adherence was estimated quarterly through the Medication Possession Ratio. We clustered patients into groups, we identified trajectories, and we described baseline characteristics. A further analysis, excluding patients with a low adherence behaviour and subsequently re-clustering, was performed. Results: We selected 3,449 patients. Females were 2,316 (67.1%). The mean age was 53.6 (standard deviation, SD 16.7). The index bDMARDs were etanercept (1,328, 38.5%), adalimumab (1,104, 32%), infliximab (299, 8.7%), golimumab (253, 7.3%), abatacept (177, 5.1%), certolizumab (156, 4.5%), and tocilizumab (132, 3.8%). Two adherence trajectories were identified: high (92.1% of patients), and low (7.9%). Younger patients were observed in the high adherence trajectory (53.3, SD 16.7, p=0.003). At baseline, conventional synthetic DMARDs (74.0%) were most frequent in the high trajectory (93%), while a significant occurrence of other gastrointestinal disorders was observed in the low adherence trajectory. When we excluded low adherent patients and re-clustered data, 3,142 patients were grouped in three trajectories: high (2,098 patients), medium-low (743), and low (301). We observed a significant distribution of infliximab in the high adherence trajectory (203, 9.7%, p=0.02) and other cardiovascular and lung disorders in the low adherence trajectory. The medium-low trajectory was characterized by wide adherence variability over time. Conclusions: Our findings showed that the majority of RA patients had a high adherence behavior over time to bDMARDs. Infliximab is the index drug more frequently reported in the high adherence trajectory, while comorbidities characterized the low adherence trajectory.