Abstract
OBJECTIVES: To examine determinants of tofacitinib discontinuation due to voluntary (i.e. patient-driven) or involuntary reasons (i.e. protocol mandated) in long-term extension (LTE) studies of patients with RA to inform clinical practice, clinical study execution and 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 geographic 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 or Latin America (vs USA or Canada) or with RF(+)/anti-CCP(+) status were significantly less likely to discontinue for voluntary reasons (P < 0.05). Small numeric differences in disease activity were observed between geographic 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 results may improve our understanding of attrition and inform future study design/execution. TRIAL REGISTRATIONS: ClinicalTrials.gov (http://clinicaltrials.gov): NCT00413699 and NCT00661661.