SAT0234 Tofacitinib, an oral janus kinase inhibitor, in the treatment of rheumatoid arthritis: safety and efficacy in open-label, long-term extension studies over 9 years
Authors: J. Wollenhaupt, J. Silverfield, E. B. Lee, K. Terry, K. Kwok, S. Strengholt, R. DeMasi, L. Wang
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background:</h3> Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). <h3>Objectives:</h3> To report tofacitinib safety and tolerability up to 114 months and clinical efficacy up to 96 months in long-term extension (LTE) studies. <h3>Methods:</h3> Data were pooled from 2 open-label studies (NCT00413699 [database locked as of March 2017]; and NCT00661661) of patients with RA who had participated in qualifying Phase 1/2/3 studies of tofacitinib. Patients received tofacitinib 5 or 10 mg twice daily (BID) as monotherapy or with background conventional synthetic (cs)DMARDs. As patients in the LTE studies were allowed to switch doses, they were assigned to the 5 mg BID group if the total daily dose (TDD) was &lt;15 mg/day, and to the 10 mg BID group if TDD was ≥15 mg/day. Primary endpoints were adverse events (AEs) and confirmed laboratory safety data. Other endpoints included clinical efficacy measures (ACR20/50/70 response rates, mean DAS28–4[ESR] score, mean HAQ-DI score and mean change from baseline in Clinical Disease Activity Index score). Safety data were included up to Month 114 and completer-analyzed efficacy data up to Month 96 (n≤100 post-Month 96). <h3>Results:</h3> Overall, 4967 patients were treated (mean [max] duration: 3.5 [9.4] years). Total tofacitinib exposure was 17,738.5 patient-years (py); 76.4% of patients maintained their initial dose. In total, 2518 patients (50.7%) discontinued (AEs: 1189 [23.9%]; insufficient clinical response: 179 [3.6%]). The most common classes of AE were infections and infestations (69.6%; exposure adjusted event rate [EAER; events per 100 py], 19.71) and musculoskeletal/connective tissue disorders (40.3%; EAER, 11.40). The most common AEs were nasopharyngitis (19.1%; EAER, 5.41), upper respiratory tract infection (17.9%; EAER, 5.07), bronchitis (12.6%; EAER, 3.58) and urinary tract infection (12.5%; EAER, 3.55). Serious AEs occurred in 29.4% of patients and serious infections (SIEs) in 8.9% of patients. Malignancies, excluding non-melanoma skin cancer, were reported in 3.0% of patients. Incidence rates (IR; patients with events per 100 py) for AEs of interest, with 95% confidence intervals, are provided in the table 1. IRs for SAEs, SIEs and malignancies through Month 114 did not increase vs reported data through Month 105.<sup>1</sup> Confirmed laboratory data are provided in the table 1. No new safety risks were identified. Clinical responses were sustained from Month 1 to Month 96 (table 1). <h3>Conclusions:</h3> In patients with RA who remained in the LTE studies, tofacitinib (5 or 10 mg BID), with or without background csDMARDs, was associated with consistent safety through Month 114 and sustained clinical efficacy through Month 96. <h3>Reference</h3> [1]Wollenhaupt J, et al. Arthritis Rheumatol2016;68(suppl 10): Abstract 1647. <h3>Acknowledgements:</h3> Study sponsored by Pfizer Inc. Medical writing support was provided by A McCluskey of CMC and funded by Pfizer Inc. <h3>Disclosure of Interest:</h3> J. Wollenhaupt Consultant for: Pfizer Inc, Speakers bureau: Pfizer Inc, J. Silverfield Grant/research support from: Pfizer Inc, Speakers bureau: Pfizer Inc, E. B. Lee Consultant for: Pfizer Inc, K. Terry Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, K. Kwok Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, S. Strengholt Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, R. DeMasi Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, L. Wang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc