Inflamm Bowel Dis. 2020 Sep 1;izaa227. doi: 10.1093/ibd/izaa227. Online ahead of print.

Bruce E Sands ¹, Jean-Frédéric Colombel ¹, Christina Ha ², Michel Farnier ³, Alessandro Armuzzi ⁴, Daniel Quirk ⁵, Gary S Friedman ⁵, Kenneth Kwok ⁶, Leonardo Salese ⁵, Chinyu Su ⁵, Pam R Taub ⁷

Author information

• ¹Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
• ²Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, Los Angeles, California, USA.
• ³PEC2, EA 7460, University of Bourgogne-Franche Comté and Department of Cardiology, CHU Dijon-Bourgogne, Dijon, France.
• ⁴IBD Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy.
• ⁵Inflammation & Immunology, Pfizer Inc, Collegeville, Pennsylvania, USA.
• ⁶Inflammation & Immunology, Pfizer Inc, New York, New York, USA.
• ⁷Division of Cardiovascular Medicine, University of California, San Diego, California, USA.

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.