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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

Wollenhaupt J, Lee EB, Curtis JR, Silverfield J, Terry K, Soma K, Mojcik C, DeMasi R, Strengholt S, Kwok K, Lazariciu I, Wang L, Cohen S. - Arthritis Res Ther. 2019 DOI: 10.1186/s13075-019-1866-2

TOF 5 mg and 10mg BID demonstrated a consistent safety profile and sustained efficacy for up to 9.5 years in this open-label LTE ORAL Sequel study.

TOF 5 mg and 10 mg BID demonstrated consistent safety (as monotherapy and combination therapy) and efficacy within this open-label LTE study of RA patients. As RA requires long-term treatment, it’s important to assess the long-term efficacy and safety of RA therapies to understand the potential lifelong impact on patient health and quality of life. This study reports the data from the global LTE ORAL Sequel study and describes the safety and efficacy of treatment with TOF 5 mg and 10 mg BID for up to 9.5 years in RA patients.

Eligible patients had previously completed a prior qualifying index study of TOF and received open-label TOF 5 mg or 10 mg BID. With Investigator discretion, adjustments to TOF or background therapy was permitted. The primary objective was to determine the long-term safety and tolerability of TOF 5 mg and 10 mg BID, whereas secondary objective was to evaluate the long-term persistence of efficacy with both TOF doses.

Infection and infestations were the most common in IR for all-cause AEs leading to discontinuations which was 6.78 (95% CI: 6.39, 7.20) and IR for SAE which was 9.03 (95% CI: 8.55, 9.53) for All-TOF. IR was higher with TOF 10 mg at 3.7 (95% CI: 3.4, 4.1) vs 5 mg at 2.3 (95% CI: 2.3, 3.3) BID for HZ. Patients receiving TOF as combination therapy had higher IR with 10 mg compared to 5 mg BID for all SI, HZ and OI (excluding TB). SI, malignancies (excluding NMSC) and HZ over time have showed to remain generally stable. ACR20, response rates were maintained over time and were generally similar between TOF 5 mg and 10 mg. HAQ-DI improved and DAS28-4(ESR) decreased at month 1 which remained stable over time in both TOF doses.

TOF 5 mg and 10mg BID demonstrated a consistent safety profile and sustained efficacy in this open-label LTE ORAL Sequel study of RA. Observed IRs for SAEs, SI, malignancies & MACE were similar to those observed in pooled data from phase 1, 2, 3, and LTE studies, and comparable to TNFi and other bDMARDs. TOF 5mg and 10mg BID provided sustained improvement in signs and symptoms of RA and improvements in physical function.