Background/Purpose: Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA. Previously, the efficacy and safety of tofacitinib were demonstrated in patients (pts) with RA in global Phase (P)2, P3, and long-term extension (LTE) studies, and in Japanese pts with RA in two P2 studies and one LTE study. Safety is being evaluated in Japanese pts with RA in an ongoing three-year post‑marketing surveillance (PMS) study. Here, we report incidence of serious infection events (SIEs), Pneumocystis jiroveci pneumonia (PCP), tuberculosis (TB), and herpes zoster (HZ) among Japanese pts with RA treated with tofacitinib, using interim PMS data.

Methods: All pts treated with tofacitinib in Japan were consecutively registered in this PMS study. Adverse events (AEs) in pts with RA receiving tofacitinib were collected throughout the PMS study (36 months; data-cut: November 5, 2017), and were coded using MedDRA ver.20.1. For SIEs, follow-up surveillance after discontinuation of tofacitinib was conducted up to Month 12, and the frequency and types of SIEs, PCP, TB, and HZ are reported for the PMS first six-month observation period. All-period data (up to 36 months) were used to calculate cumulative incidence rates (IRs: pts with events/100 pt-years [PY]) over time for HZ and SIEs during treatment +28 days.

Results: In total, 3929 pts received tofacitinib (3956.4 PY of exposure at 36 months). At baseline, 80.5% of pts were female; mean age (standard deviation [SD]) was 62.7 (12.6) years; 32.6% of pts were ≥70 years. In the six-month observation period, 2041 AEs (all causality) were reported in 1313 (33.4%) pts. The most frequently reported AE by system organ class was Infections and Infestations (n=493; 12.5%) and the most frequently reported AE by preferred term was HZ (n=145; 3.7%), including one HZ meningoencephalitis (serious) and two disseminated HZ (one serious; one non‑serious). PCP was reported in 16 (0.4%) pts (15 serious; one non-serious). There were three TB cases (including one serious bone tuberculosis); no pts with TB had received chemoprophylaxis with isoniazid before starting tofacitinib. At Month six, 130 (3.3%) pts had SIEs; most common by preferred term were HZ (n=24; 0.6%), pneumonia (n=23; 0.6%), PCP (n=15; 0.4%), and pneumonia bacterial (n=10; 0.3%). The IRs of HZ and SIE were highest at Months 1-3 and stabilized after Month 12 (all-period data; overall IR was 6.81 [n=264; 3876.0 PY] and 5.38 [n=212; 3941.3 PY] for HZ and SIEs, respectively [Figure]).

Conclusion: This interim analysis of PMS data from Japan did not reveal any new or unexpected safety risks vs tofacitinib RA clinical trials, although exposure time was short. HZ IR was similar to that reported in P2, P3, and LTE trials in Japanese pts with RA; SIE IR was within the range of IRs in prior PMS studies of RA biologic treatment.