THU0238 Tofacitinib, an Oral Janus Kinase Inhibitor: Safety Comparison in Patients with Rheumatoid Arthritis and an Inadequate Response to Nonbiologic or Biologic Disease-Modifying Anti-Rheumatic Drugs
Authors: G. Burmester, C. Charles-Schoemann, J. Isaacs, T. Hendrikx, K. Kwok, S. H. Zwillich, R. Riese
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Tofacitinib is a novel, oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). <h3>Objectives</h3> This analysis provides comparative safety data on the incidence of safety events for patients (pts) with an inadequate response (IR) to a nonbiologic disease-modifying antirheumatic drug (DMARD)-IR versus pts with an IR to a biologic DMARD (bDMARD)-IR. <h3>Methods</h3> The primary comparison was performed on pooled data from 5 randomised, controlled Phase 3 (P3) studies in RA pts treated with tofacitinib 5 mg or 10 mg BID for 6 to 12 months. Supportive analyses were conducted on 2 pooled open-label long-term extension (LTE) studies. All pts enrolled were nonbiologic or biologic DMARD-IR. <h3>Results</h3> In the pooled P3 studies, 2389 tofacitinib-treated pts with 1783 pt-years (pt-yrs) of exposure were analysed in the DMARD-IR population and 641 pts with 315 pt-yrs of exposure in the bDMARD-IR group. Baseline demographics were generally similar, albeit the bDMARD-IR group was generally older, heavier and had fewer Asian pts. Compared with the DMARD-IR, the bDMARD-IR population exhibited increases in the rate (events/100 pt-yrs) of serious adverse events (SAE) (12.3 [95% confidence interval (CI) 9.0, 16.9] vs 9.9 [8.6, 11.5]) and discontinuations due to adverse events (AE DC) (15.0 [95% CI 11.3, 20.0] vs 9.6 [7.7, 12.1) in both tofacitinib treatment arms and in placebo. There were four adalimumab pts (and 0 events) that were bDMARD-IR. The rates of deaths, serious infections (SI), malignancies and major adverse cardiovascular events were similar across the populations (Table). LTE studies included 2715 pts with 3588 pt-yrs of exposure in the DMARD-IR population and 566 pts with 514 pt-yrs of exposure in the bDMARD-IR group. As compared with the DMARD-IR, the bDMARD-IR population showed increases (events/100 pt-yrs [95% CI]) in rates of SAEs (14.6 [11.6, 18.4] vs 10.2 [9.2, 11.3]); AE DC (10.0 [7.6, 13.1] vs 6.8 [6.0, 7.7]); and SI (4.7 [3.1, 7.0] vs 2.7 [2.2, 3.3]). The rates of the other safety events were similar. <h3>Image/graph</h3> <h3>Conclusions</h3> Event rates for important safety events for both DMARD-IR and bDMARD-IR pts are within the ranges observed with biologic therapies approved for treatment of RA with some differences noted in SI (LTE only), SAE and AE DC favouring the DMARD-IR population. <h3>Disclosure of Interest</h3> G. Burmester Grant/research support from: Abbott, BMS, MSD, Pfizer Inc., Roche, UCB, Consultant for: Abbott, BMS, MSD, Pfizer Inc., Roche, UCB, Speakers bureau: Abbott, BMS, MSD, Pfizer Inc., Roche, UCB, C. Charles-Schoemann Grant/research support from: Pfizer Inc., Consultant for: Pfizer Inc., Speakers bureau: Pfizer Inc., J. Isaacs Consultant for: Pfizer Inc., T. Hendrikx Shareholder of: Pfizer Inc., Employee of: Pfizer Inc., K. Kwok Shareholder of: Pfizer Inc., Employee of: Pfizer Inc., S. Zwillich Shareholder of: Pfizer Inc., Employee of: Pfizer Inc., R. Riese Shareholder of: Pfizer Inc., Employee of: Pfizer Inc.