Determinants of tofacitinib discontinuation in adult patients with rheumatoid arthritis during long-term extension studies up to 9.5 years

Abstract

Abstract Objectives To examine determinants of tofacitinib discontinuation due to voluntary (ie patient-driven) or involuntary reasons (ie protocol-mandated) in long-term extension (LTE) studies of patients with rheumatoid arthritis (RA) to inform clinical practice, clinical study execution/data capture. Methods This post hoc analysis used pooled data from patients receiving tofacitinib 5 or 10 mg twice daily (BID) in LTE studies. Outcomes included time to voluntary/involuntary discontinuation (and baseline predictors), including by geographical region. Exposure-adjusted event rates (EAERs) were calculated for adverse events (AEs), serious AEs (SAEs) and discontinuations due to AEs/SAEs. Results Of 4967 patients, 2463 (49.6%) discontinued (1552/4967 [31.2%] voluntarily, 911/4967 [18.3%] involuntarily) and 55 (1.1%) died over the course of 9.5 years. When involuntary discontinuation was present as a competing risk for voluntary discontinuation, patients who stayed on combination therapy, and with higher patient-assessed pain were significantly more likely to discontinue for voluntary reasons (p < 0.05). Older patients, those enrolled in Asia/Europe/Latin America (vs US/Canada) or with rheumatoid factor+/anti-cyclic citrullinated antibody+ status, were significantly less likely to discontinue for voluntary reasons (p < 0.05). Small numeric differences in disease activity were observed between geographical regions in patients who discontinued or completed the studies. EAERs were generally higher for tofacitinib 10 vs 5 mg BID, irrespective of discontinuation reason. Conclusion The factors associated with voluntary/involuntary discontinuation of tofacitinib suggest that treatment persistence in RA studies is partly predictable, which may be reflected in clinical practice. Applying these learnings may improve understanding of attrition and inform future study design/execution.