The incidence rates of hypertension-related adverse events (AEs) and major adverse cardiovascular events (MACE) were low in a cohort of individuals treated with tofacitinib for psoriatic arthritis (PsA), according to data published in Arthritis Care & Research. In addition, increases in serum lipid level after tofacitinib exposure were consistent with prior research.
Investigators abstracted data from two phase 3 studies and 1 long-term extension study of patients from the phase 3 studies. Each study investigated the cardiovascular (CV) effect of tofacitinib exposure on adults (≥age 18) with PsA. Study participants who received ≥1 dose of tofacitinib 5 or 10 mg twice daily (BID) were included in the pooled analysis (n=783).
Extracted outcome measures included fasting lipid levels, blood pressure, hypertension-related AEs, and MACE. Incidence rates were reported for discrete data, adjusted for person-time on study drug. Mean changes from baseline in continuous data were summarized descriptively.
The total cohort exposure to tofacitinib was 1237.9 person-years, with a median exposure of 594 (range, 1 to 1196) days. Demographic data were generally similar between phase 3 study participants; the mean age ranged from 48.4±12.5 years to 49.5±12.4, and the majority (range, 50.8% to 57.6%) were women.
At baseline, the mean duration of diagnosed PsA ranged from 7.5±6.6 years to 8.6±7.9 years, and patients had generally high disease activity. Mean percentage increases from baseline in low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels ranged from 9.2% to 14% for tofacitinib 5 and 10 mg bid at 3 months (LDL-C, 9.2% and 14%; HDL-C, 10% and 14%, respectively).
These values remained stable through month 6 in both the 5-mg and 10-mg BID groups (LDL-C, 9.9% and 14.3%; HDL-C, 9% and 13.9%, respectively).
Similar mean changes from baseline were also observed in total cholesterol (TC) and triglycerides (TGs) at 3 months (TC 8.5% for 5 mg and 12.1% for 10 mg BID; TG 9.3% and 16.8%, respectively) and 6 months (TC 8.2% and 13.7%; TGs 6.6% and 20.4%, respectively).
No significant changes were observed in lipid ratios, including LDL-C/HDL-C, TC/HDL-C, LDL-C/HDL-C, and TC/HDL-C. Across the pooled cohort, 58 patients (7.4%) reported hypertension-related AEs; incidence rates were similar across tofacitinib dosages.
These data offer detailed information on the CV effect of tofacitinib exposure. Serum lipid level increases did not exceed rates observed in prior research on patients with rheumatoid arthritis and psoriasis. Long-term follow-up for risk for hypertension-related AEs and MACE is ongoing, although according to this study the risk is low.
Gladman DD, Charles-Schoeman C, McInnes IB, et al. Changes in lipid levels and incidence of cardiovascular events following tofacitinib treatment in patients with psoriatic arthritis: a pooled analysis across phase 3 and long-term extension studies [published online May 21, 2019]. Arthritis Care Res. doi:10.1002/acr.23930