SAN DIEGO, CA—Patients with rheumatoid arthritis and diabetes mellitus had no increase in mean fasting blood glucose levels after 3 months of treatment with tofacitinib, a novel oral Janus kinase inhibitor, according to a pooled analysis of five phase 3 trials reported at the 2013 ACR/ARHP Annual Meeting.
In addition, “the number of patients with diabetes mellitus whose fasting blood glucose increased to ≥126mg/dL was limited and similar to that observed in patients receiving placebo,” noted William F. C. Rigby, MD, of Geisel School of Medicine at Dartmouth and Dartmouth Hitchcock Medical Center, Lebanon, NH, and colleagues.
Both rheumatoid arthritis and diabetes mellitus are associated with lipid changes and an increased risk of infection.
Dr. Rigby and colleagues evaluated selected safety end points—including changes in fasting blood glucose, lipids, and risk of infection—in a post-hoc pooled analysis of five tofacitinib Phase 3 studies in 2430 patients who had inadequately responded to disease-modifying anti-rheumatic drugs (DMARDs). Of these, 8.7% (211) had diabetes mellitus; 8.9% (108/1216) who received tofacitinib 5mg twice daily and 8.5% (103/1214) who received tofacitinib 10mg twice daily; in addition, 7.0% (48/681) of patients who received placebo had diabetes mellitus.
At baseline, 49.1% (tofacitinib 5mg twice daily), 46.6% (tofacitinib 10mg twice daily), and 50% (placebo) of patients with diabetes mellitus used glucocorticoids. “Baseline demographic characteristics were generally balanced across treatment groups, although compared with patients without diabetes mellitus, patients with diabetes mellitus tended to be older, had a slightly higher body mass index, were more likely to be taking lipid-lowering medications and were more likely to be smokers or ex-smokers,” they noted.
Mean baseline fasting blood glucose in patients with diabetes mellitus was 138.0mg/dL in the tofacitinib 5mg twice daily group, 129.8mg/dL in the tofacitinib 10mg twice daily group, and 138.9mg/dL in the placebo group. At Month 3, these values were 126.1mg/dL, 124.0mg/dL, and 129.5mg/dL, respectively.
Across all treatment groups and for both patients with and without diabetes mellitus, a ≤5% maximum increase from baseline in fasting blood glucose was reported in the majority of patients.
The shift analysis of fasting blood glucose data from 82 patients in the tofacitinib 5mg twice daily group with diabetes mellitus showed 10 patients moved from lower to higher American Diabetes Association category at baseline at Month 1 or 3, while 19 patients moved from higher to lower category (53 with no change).
For patients with diabetes mellitus in the tofacitinib 10mg twice daily group, numbers moving to higher, lower, or no change in category were 19, 13, and 46, respectively. Corresponding numbers for placebo patients with diabetes mellitus were 9, 9, and 25.
Increases in mean low density lipoprotein and triglyceride levels were observed at Month 3 in patients treated with tofacitinib; the same pattern was observed in patients both with and without diabetes mellitus.
During the 3-month follow-up, 23.1% of patients with diabetes mellitus in the tofacitinib 5mg twice daily group had ≥1 infection; as did 21.4% in the tofacitinib 10mg twice daily group and 25.0% in the placebo group. In patients without diabetes mellitus, the corresponding proportions were 21.0%, 21.8%, and 18.6%, respectively. Rates of serious infections were similar across treatment groups and between patients with and without diabetes mellitus.