(CSPOT24) Trajectories of adherence to biological drugs in patients with inflammatory bowel diseases: the VALORE project

Background: Biological-based drug treatments have been introduced to treat inflammatory bowel diseases (IBDs) to obtain an early remission and to prevent relapse. In chronic diseases, non-adherence to treatment is one of the major obstacles to the achievement of patient’s health goals. Being adherence a dynamic process, longitudinal methods are appropriate for capturing individual changes over time.

Objectives: To identify and describe trajectories of adherence to biological drugs in patients with IBDs and to identify determinants of adherence, in Italian real world setting.

Methods: We conducted a retrospective cohort study on 12 Italian regions including new users of biological drugs with IBD within 2010-2022 and followed patients for three years. We calculated the adherence for each patient monthly, over the 3-year follow-up period through the proportion of days covered (PDC) using the Defined Daily Dose (DDD) for drug coverage. Trajectories of adherence to biologics were identified according to a three-steps method: i) computation of 24 statistical measures, summarizing the individual variability of adherence; ii) principal component analysis, selecting the measures that explain the largest proportion of variance in data; iii) cluster analysis, grouping patients with similar longitudinal pattern of drug use. We identified determinants of adherence to biologics using a multinomial and multivariate regression.

Results: We included 20,150 patients in the final cohort, mostly male (56%), young (93%), and with Crohn’s disease (58%). We identified three trajectories of adherence to biologics for IBDs: one group (19% of the cohort) maintained high adherence throughout the observation period, while the largest group (46%) initially reduced adherence, stabilizing around 70%. The remaining group (35%) gradually decreased adherence over the entire follow-up, reaching 20%. Being female (OR 1.52, 95% CI 1.40-1.65), and elderly (1.44, 1.21-1.70) were positively associated with low adherence than high adherence. Instead, patients starting biologics treatment with a biosimilar (0.47, 0.42-0.52) and those patients starting with etanercept, golimumab, infliximab, vedolizumab and ustekinumab compared to adalimumab, were negatively associated with low adherence.

Conclusions: We observed a considerable proportion of patients who gradually discontinued biological treatment within the first three years of use, while another group maintained suboptimal adherence. Adalimumab as index drug was associated with low adherence, whereas starting with a biosimilar drug was associated with high adherence. This study is important for guiding clinical practice, allowing targeted actions towards less adherent patients.