Background/Purpose: Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA. The objective of this analysis was to report tofacitinib safety and tolerability and clinical efficacy in long-term extension (LTE) studies over 96 months (Mo).

Methods: Data were pooled from 2 open-label studies (NCT00413699 [ongoing; database unlocked at January 2016 data-cut] and NCT00661661) of patients (pts) with RA who had participated in Phase 1/2/3 tofacitinib studies. Pts received tofacitinib 5 or 10 mg twice daily (BID) as monotherapy or with background DMARDs. Primary endpoints: adverse events (AEs) and confirmed laboratory safety data. Secondary endpoints included clinical efficacy measures (ACR20/50/70 response rates, DAS28-4[ESR], HAQ-DI, and clinical disease activity index). Safety data were included up to Mo 105 and efficacy data up to Mo 90 (n≤100 at Mo 96).

Results: 4,967 pts were treated (mean [max] duration: 1,215 [3,182] days). Total tofacitinib exposure was 16,711 pt-years (py); 77.4% of pts maintained initial dose. In total, 2,370 pts (47.7%) discontinued (AEs: 1,131 [22.8%]; insufficient clinical response: 175 [3.5%]). Most common AE classes: infections and infestations (68.9%) and musculoskeletal/connective tissue disorders (39.0%). Most common AEs: nasopharyngitis (18.7%), upper respiratory tract infection (17.2%), bronchitis and urinary tract infection (12.2% each). Serious AEs occurred in 28.6% of pts, and serious infections (SIEs) in 8.8% of pts. Malignancies, excluding non-melanoma skin cancer, were reported in 3.0% of pts. Incidence rates (IR; pts with events per 100 py) for AEs of interest, with 95% confidence intervals (CIs), are provided in Table 1. IRs for SIEs and malignancies through Mo 105 did not increase vs reported data through Mo 96.¹ Confirmed laboratory data are provided in Table 1. No new safety risks were identified. Clinical responses were sustained from Mo 1 to Mo 90 (Table 2).  

Conclusion: In patients with RA who remained in LTEs, tofacitinib (5 or 10 mg BID) with or without background DMARDs was associated with consistent safety through Mo 105, and sustained clinical efficacy through Mo 90. Reference:

1. Wollenhaupt J et al. Arthritis Rheumatol 2015; 67 (suppl 10): Abstract 1645.