Safety and efficacy of tofacitinib for up to 9.5?years in the treatment of rheumatoid arthritis: final results of a global, open-label, long-term extension study

摘要

Background: Final data are presented for the ORAL Sequel long-term extension (LTE) study evaluating the safetyand efficacy of tofacitinib 5 mg and 10 mg twice daily (BID) for up to 9.5 years in patients with rheumatoid arthritis(RA).Methods: Eligible patients had previously completed a phase 1, 2, or 3 qualifying index study of tofacitinib andreceived open-label tofacitinib 5 mg or 10 mg BID. Stable background therapy, including csDMARDs, was continued;adjustments to tofacitinib or background therapy were permitted at investigators’ discretion. Assignment to dosegroups (5 mg or 10 mg BID) was based on patients’ average total daily dose. The primary objective was todetermine the long-term safety and tolerability of tofacitinib 5 mg and 10 mg BID; the key secondary objective wasto evaluate the long-term persistence of efficacy.Results: Between February 5, 2007, and November 30, 2016, 4481 patients were enrolled. Total tofacitinib exposurewas 16,291 patient-years. Safety data are reported up to month 114 for all tofacitinib; efficacy data are reported upto month 96 for tofacitinib 5 mg BID and month 72 for 10 mg BID (with low patient numbers limiting interpretationbeyond these time points). Overall, 52% of patients discontinued (24% due to adverse events [AEs] and 4% due toinsufficient clinical response); the safety profile remained consistent with that observed in prior phase 1, 2, 3, or LTEstudies. The incidence rate (IR; number of patients with events per 100 patient-years) for AEs leading to discontinuationwas 6.8. For all-cause AEs of special interest, IRs were 3.4 for herpes zoster, 2.4 for serious infections, 0.8 for malignanciesexcluding non-melanoma skin cancer, 0.4 for major adverse cardiovascular events, and 0.3 for all-cause mortality. Clinicallymeaningful improvements in the signs and symptoms of RA and physical functioning, which were observed in the indexstudies, were maintained.