Background/Purpose: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Efficacy and safety of tofacitinib have been shown in patients (pts) with RA in global Phase (P) 2, P3 (one of which included Japanese pts) and a long-term extension (LTE) study and in two P2 and one LTE study in Japanese pts. We evaluated safety of tofacitinib following drug approval in Japanese pts with RA using all-case post-marketing surveillance (PMS) data.

Methods: PMS is a regulatory requirement in Japan; an interim analysis of safety data from an ongoing 3-year PMS study was conducted (4 Mar 2017 data-cut). All Japanese pts with RA receiving tofacitinib were consecutively and prospectively registered in the PMS study and were monitored. Follow-up surveillance after discontinuation of tofacitinib was implemented for 3 years for all adverse events (AEs) from the date of treatment initiation with tofacitinib. A 6-month interim analysis of all AEs and serious AEs (SAEs) was conducted. For AEs of special interest, all-period data was used to calculate cumulative incidence rates (IRs) over time (IRs: pts with events /100 pt-years [pt-yrs]) for herpes zoster (HZ) and serious infection events (SIEs) during treatment +28 days, and for malignancies during the observational period.

Results: Overall, 2882 tofacitinib-treated pts were enrolled and included in the 6-month interim safety analysis: 79.9% were female, mean age 62.6 yrs, with 32.0% pts ≥70 yrs and 1241.4 pt-yrs of exposure. Of these, 686 pts (23.8%) discontinued treatment, mainly due to AEs (276 pts; 9.6%) or lack of effectiveness (260 pts; 9.0%; multiple reasons allowed). At least one AE was observed in 965 pts (33.5%); infections were observed in 367 pts (12.7%); the most frequent AEs were HZ (98 pts; 3.4%) and hepatic function abnormal (48 pts; 1.7%). SAEs occurred in 221 pts (7.7%); the most frequent SAEs were pneumonia (20 pts; 0.7%), HZ (16 pts; 0.6%), interstitial lung disease (14 pts; 0.5%) and condition aggravated (12 pts; 0.4%); serious infections occurred in 101 pts (3.5%). Malignancy (all causality) was reported in 21 pts (0.7%); ovarian cancer, pancreatic carcinoma, lung neoplasm, colon cancer, breast cancer, diffuse large B‑cell lymphoma and lymphoproliferative disorder all occurred in 2 pts (0.07%) each. There were 16 deaths (0.6%) during the 6-month observed period; the most common causes of death (including pts with multiple causes listed) were infection (5 cases, all respiratory infections), malignancy (4 cases) and interstitial lung disease (3 cases). For AEs of special interest from all-period data during treatment +28 days, the IR of HZ (serious and non-serious) was 6.43/100 pt-yrs (160 pts; 2489.5 pt-yrs) and SIEs 5.96/100 pt-yrs (150 pts; 2517.0 pt-yrs), and during the observational period IR malignancy was 1.39/100 pt-yrs (42 pts; 3014.1 pt-yrs).

Conclusion: For this interim analysis, AEs during the initial 6-month treatment period from PMS reports of tofacitinib in Japanese pts did not reveal any new or unexpected safety signals vs the tofacitinib RA clinical program. Final results from this PMS study are awaited in order to make definitive conclusions on the safety profile of tofacitinib in these pts.