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

Abstract

Background:Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA).Objectives:To report tofacitinib safety and tolerability up to 114 months and clinical efficacy up to 96 months in long-term extension (LTE) studies.Methods: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 <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).Table 1Safety data (Month 114) and clinical efficacy outcomes (up to Month 96; as observed) in LTE studies of tofacitinib in patients with RAResults: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 105.1 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).Conclusions: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.Reference[1]Wollenhaupt J, et al. Arthritis Rheumatol2016;68(suppl 10): Abstract 1647.Acknowledgements:Study sponsored by Pfizer Inc. Medical writing support was provided by A McCluskey of CMC and funded by Pfizer Inc.Discl...

Long‐term safety and tolerability of oral tofacitinib in patients with Crohn’s disease: results from a phase 2, open‐label, 48‐week extension study

“…Infections were reported in approximately half of patients receiving tofacitinib in this study. The safety profile reported here is generally consistent with previous studies in rheumatoid arthritis with up to 114 months’ observation . No new safety signals emerged and, as in the rheumatoid arthritis programme, the most frequently occurring adverse events were infections, including nasopharyngitis …”

“…with up to 114 months' observation. 13 No new safety signals emerged and, as in the rheumatoid arthritis programme, the most frequently occurring adverse events were infections, including nasopharyngitis. 13 Rates of discontinuation due to adverse events and insufficient clinical response were higher for tofacitinib 10 mg b.d.…”

Benefit–risk profile of tofacitinib in patients with moderate‐to‐severe chronic plaque psoriasis: pooled analysis across six clinical trials

“…Tofacitinib 5 mg BID and 10 mg BID were generally well tolerated, and safety events were similar to those reported with tofacitinib in rheumatoid arthritis, ulcerative colitis and psoriatic arthritis . Only one study is available comparing tofacitinib head to head with another psoriasis treatment, and comparisons between treatments must therefore be interpreted cautiously.…”

Tofacitinib in Rheumatoid Arthritis: Lack of Early Change in Disease Activity and the Probability of Achieving Low Disease Activity at Month 6

“…The efficacy and safety of tofacitinib 5 and 10 mg twice daily, administered as monotherapy or in combination with csDMARDs, mainly MTX, in patients with moderately to severely active RA, have been demonstrated in phase II (15)(16)(17)(18)(19) and phase III (7,(20)(21)(22)(23)(24) studies of up to 24 months' duration and in long-term extension studies with up to 114 months of observation (25)(26)(27). The efficacy and safety of tofacitinib 5 and 10 mg twice daily, administered as monotherapy or in combination with csDMARDs, mainly MTX, in patients with moderately to severely active RA, have been demonstrated in phase II (15)(16)(17)(18)(19) and phase III (7,(20)(21)(22)(23)(24) studies of up to 24 months' duration and in long-term extension studies with up to 114 months of observation (25)(26)(27).…”

“…Tofacitinib is an oral JAK inhibitor for the treatment of RA. The efficacy and safety of tofacitinib 5 and 10 mg twice daily, administered as monotherapy or in combination with csDMARDs, mainly MTX, in patients with moderately to severely active RA, have been demonstrated in phase II (15)(16)(17)(18)(19) and phase III (7,(20)(21)(22)(23)(24) studies of up to 24 months' duration and in long-term extension studies with up to 114 months of observation (25)(26)(27).…”