Tofacitinib therapy for ulcerative colitis (UC) did not alter lipid levels or ratios from baseline among the majority of patients. These findings, from a systematic review, were published in Inflammatory Bowel Disease.
Data from a phase 3, open-label, long-term extension study were combined with information gathered during a relevant literature search and the most up-to-date expert guidelines for interpretation of lipid data after tofacitinib therapy for UC.
Generally, patients with inflammatory bowel disease (IBD) have an increased risk for mortality because of cardiovascular (CV) complications. Despite this fact, patients with IBD tend to have a lower instances of traditional CV risk factors.
Tofacitinib treatment is associated with increased lipid levels during the beginning of therapy among other patient populations. If a similar pattern of altered lipid levels were observed among patients with IBD, tofacitinib may not be suitable for use among these patients.
During a phase 3 trial, 1124 patients with UC received 5- or 10-mg doses of tofacitinib for ≤6.8 years. Investigators used a Reynolds Risk Score to predict future myocardial infarction, stroke, or heart disease within the next 10 years. After 8 weeks of tofacitinib therapy, participants receiving the 10-mg dose had an average Reynolds Risk Score of 2.1, and serum levels of total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol were not significantly increased from baseline.
The incidence rate of a major myocardial event was reported as 0.26/100 person-years. Researchers observed a total of 7 major myocardial events, including 1 fatal incident of aortic dissection; however, they reported that 5 of the 7 individuals had multiple CV risk factors at baseline.
Current guidelines for treatment indicated that before starting tofacitinib therapy, patients should be stratified for CV risk features. Patients with increased risk factors (eg, cardiovascular disease [CVD], family history, diabetes, chronic kidney disease) should have their lipid levels screened before treatment. All patients should be monitored for abnormal lipid levels at 4 to 8 weeks after starting therapy.
At 8 weeks of tofacitinib treatment, investigators observed lipid levels stabilizing. At this time, patients with normal lipid levels may continue treatment. For patients with abnormal lipid profiles, lifestyle interventions and secondary causes for hyperlipidemia should be considered. If abnormal lipid levels persist, lipid-lowering therapy should be considered, and possibly a referral to a specialist.
To conclude, the systematic review authors asserted that patients with IBD have an increased risk for CVD, possibly because of systemic inflammation. Therefore, treatment with a therapy known to alter lipid levels should be approached with caution, especially among patients with other known risk factors. Despite evidence that tofacitinib does not significantly increase lipid levels among patients with UC, clinicians treating patients with IBD should stay up-to-date with expert guidelines for managing hyperlipidemia and follow all clinical guidance.
Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.
Sands BE, Colombel JF, Ha C, et al. Lipid profiles in patients with ulcerative colitis receiving tofacitinib–implications for cardiovascular risk and patient management [published online September 1, 2020]. Inflamm Bowel Dis. doi: 10.1093/ibd/izaa227