Lipid Profiles in Patients with Ulcerative Colitis Receiving Tofacitinib - Implications for Cardiovascular Risk and Patient Management

Abstract

Background: Patients with ulcerative colitis (UC) are at elevated risk of cardiovascular disease vs the general population, despite a lower prevalence of traditional risk factors, including hyperlipidemia. Mechanistic studies in patients with rheumatoid arthritis and psoriasis suggest that tofacitinib restores serum lipids to preinflammation levels by reversing inflammation-induced cholesterol metabolism changes. We reviewed data on lipid levels and cardiovascular events, alongside recommendations for managing lipid levels during tofacitinib treatment in patients with UC, based on up-to-date expert guidelines. Methods: Data were identified from a phase 3/open-label, long-term extension (OLE) tofacitinib UC clinical program (cutoff May 27, 2019). Literature was identified from PubMed (search terms "lipid,""cholesterol,""lipoprotein,""cardiovascular,""inflammation,""atherosclerosis,""tofacitinib,""rheumatoid arthritis,""psoriasis,""inflammatory bowel disease,""ulcerative colitis,""hyperlipidemia,"and "guidelines") and author knowledge. Data were available from 4 phase 3 clinical trials of 1124 patients with moderately to severely active UC who received?≥1 dose of tofacitinib 5 or 10 mg twice daily in induction (two identical trials), maintenance, and OLE studies (treatment duration?≤6.8 years; 2576.4 patient-years of drug exposure). Results: In the OLE study, tofacitinib treatment was not associated with major changes from baseline in total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, total cholesterol/high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol/high-density lipoprotein cholesterol, with lipid levels and ratios generally remaining stable over time. The major adverse cardiovascular events incidence rate was 0.26/100 patient-years (95% confidence interval, 0.11-0.54). Conclusions: Lipid levels and ratios remained generally unchanged from baseline in the OLE study after tofacitinib treatment, and major adverse cardiovascular events were infrequent. Long-term studies are ongoing. ClinicalTrials.gov identifiers: NCT01465763, NCT01458951, NCT01458574, NCT01470612