Background Tofacitinib is a novel, oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA).
Objectives 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.
Methods 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.
Results 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.
Conclusions 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.
Disclosure of Interest 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.