Background/Purpose: Tofacitinib is a novel, oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Studies have shown an increased prevalence of diabetes mellitus (DM) in patients (pts) with RA. Nearly 9% of pts enrolled into Phase 3 (P3) studies of tofacitinib in RA also had DM. Both RA and DM are associated with lipid changes and an increased risk of infection. This analysis evaluated selected safety endpoints in pts with and without DM receiving tofacitinib for RA.

Methods: Safety endpoints, including changes in fasting blood glucose (FBG), lipids and risk of all infections (regardless of severity), were evaluated in a post-hoc pooled analysis of five tofacitinib P3 studies in DMARD inadequate responders. Baseline (BL) clinical characteristics and lab data, and follow-up lipid data at Month (Mo) 3, were available for all studies. Follow-up FBG data were available for four studies of tofacitinib with background nonbiologic DMARDs. Categorical changes (defined by the American Diabetes Association [ADA]) in FBG vs BL were compared using shift analyses.

Results: Of 2430 pts who received tofacitinib, 8.7% (211) had DM: 8.9% (108/1216) 5 mg BID; 8.5% (103/1214) 10 mg BID. Additionally, 7.0% (48/681) of pts receiving placebo (PBO) had DM. At BL, 49.1% (tofacitinib 5 mg BID), 46.6% (tofacitinib 10 mg BID), and 50% (PBO) of pts with DM used glucocorticoids.

Mean BL FBG in pts with DM was 138 mg/dL, 129.8 mg/dL and 138.9 mg/dL in the tofacitinib 5 mg BID, 10 mg BID and PBO groups, respectively. Corresponding values at Mo 3 were 126.1 mg/dL, 124.0 mg/dL and 129.5 mg/dL. The shift analysis of FGB data from 82 tofacitinib 5 mg BID pts with DM showed 10 pts moved from lower to higher ADA category at BL at Mo 1 or 3, while 19 pts moved from higher to lower category (53 with no change, see Table). For tofacitinib 10 mg BID pts with DM, numbers moving to higher, lower, or no change in category were 19, 13, and 46, respectively. Corresponding numbers for PBO pts with DM were 9, 9, and 25 (not shown).

Increases in mean low density lipoprotein (LDL) and triglyceride (TG) levels were observed at Mo 3 in pts treated with tofacitinib, as reported previously, although the same pattern was seen in pts with and without DM. During 3 Mo of follow-up 23.1%, 21.4% and 25.0% of pts with DM in the tofacitinib 5 mg BID, 10 mg BID and PBO groups, respectively, had ≥1 infection. Corresponding proportions in pts without DM were 21.0%, 21.8% and 18.6%.

Conclusion: In the P3 studies evaluated, pts with RA and DM showed no increase in mean FBG levels after 3 Mo of tofacitinib therapy; the number of pts with DM whose FBG increased to ≥126 mg/dL was limited and similar to that observed in pts receiving PBO. Mean increases in LDL and TG were numerically similar in pts with and without DM. The proportion of tofacitinib-treated pts who experienced ≥1 infection, regardless of severity, was numerically similar between pts with and without DM.