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

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 RFþ/anti-CCPþ 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. What does this mean for patients? Rheumatoid arthritis (RA) is a disease that causes swollen and painful joints. Tofacitinib is a medicine used to treat RA. Long-term clinical studies of tofacitinib have lasted up to 9.5 years. Over that long time period, continued use of tofacitinib varied considerably, just like in real life. We found that we could partly predict why patients stop taking tofacitinib during these studies. A total of 4967 patients took tofacitinib in long-term clinical studies. In these studies, one in three decided to stop tofacitinib and one in five were told to stop tofacitinib by the study doctor when they met certain conditions that were explained in the study plan. Patients with self-assessed pain and patients taking tofacitinib with other RA medicines were more likely to decide to stop taking tofacitinib, as were patients in the USA and Canada (when compared with those in Asia, Europe and Latin America). A patient’s decision to stop tofacitinib was not strongly related to how well their disease was controlled. Side effects (adverse events) were not the main reason that patients decided to stop taking tofacitinib. Older patients and those with poor prognostic features (rheumatoid factor and anti-cyclic citrullinated protein antibodies in their blood) were less likely to decide to stop tofacitinib. This analysis will help researchers to better design RA clinical studies in the future and understand the influence of differences between countries in predicting who continues in a trial and who drops out.