Hypertensive Emergency After Initiating Ozanimod: A Case Report

To the Editors,

Ozanimod was recently approved for treatment of moderately to severely active ulcerative colitis (UC).^1–3 We present a case report of hypertensive crisis after initiating ozanimod that resolved after discontinuation.

A 70-year-old woman with moderately to severely active left-sided UC initiated ozanimod. She had been treated with mesalamine and then vedolizumab but did not achieve remission, with persistent urgency, rectal bleeding, and 8 bowel movements/day. Pre-ozanimod, colonoscopy confirmed diffuse active inflammation (endoscopic Mayo score of 2); stool calprotectin was 1373 mcg/mL. Past medical history was notable for essential hypertension, myocardial infarction, and breast cancer in remission. She had no contraindications to ozanimod and completed all baseline screening. Blood pressure (BP) before initiation ranged 110s-150s/70-90s mmHg, with a baseline heart rate (HR) at 75 beats per minute. Her antihypertensive regimen included 25 mg of losartan daily and 25 mg of metoprolol succinate daily. After 3 months of ozanimod, she achieved clinical remission but developed new headaches and elevation of her systolic BP to >200 mmHg and diastolic BP >90 mmHg. The patient reported adherence to a restricted tyramine diet <150 mg/day and antihypertensive regimens. Ozanimod was discontinued and after 2 months; her BP returned to baseline control.

Rise in BP with ozanimod has been estimated with an increase of 3.7 mmHg during induction and 5.1 mmHg in the maintenance phase.² The phase 3 TRUE NORTH Trial found hypertension occurring in 1.5% to 2.0% of patients receiving ozanimod compared with 1.3% in the placebo group.³ One patient in the ozanimod group developed hypertensive crisis on day 1 of therapy and another during the maintenance phase; both resolved without discontinuation of therapy. In the safety analysis for multiple sclerosis trials, BP elevations occurred 3 months after starting therapy, and hypertension was observed in 3.4% of the participants, with 0.2% developing hypertensive crisis.⁴

Our patient’s elevated BP resolved 2 months after ozanimod discontinuation. This is likely due to the pharmacokinetics of ozanimod. The half-life of ozanimod is 21 hours; however, the active metabolite CC1084037 has a half-life of 11 days, indicating elimination of ozanimod may take roughly 55 days.^1,2 This case presents development of hypertensive urgency in a patient with essential hypertension that resolved 2 months after discontinuation of ozanimod. Prescribers should be aware of this rare complication and the timeline for resolution. Furthermore, it is of interest that this patient did not respond to vedolizumab, a leukocyte trafficking inhibitor, but did respond to ozanimod which has a mechanism that similarly effects lymphocytes migration.

Author Contributions

Drs. Choi, Puangampai, Rubin, and Cleveland contributed to the design of the letter, wrote and revised the letter, and gave final approval and are accountable for the information presented.

Funding

None

Conflicts of Interests

D.R. has received grant support from Takeda and has served as a consultant for Abbvie, Abgenomics, Allergan Inc., Biomica, Boehringer Ingelheim Ltd., Bristol-Myers Squibb, Celgene Corp/Syneos, Check-cap, Dizal Pharmaceuticals, GalenPharma/Atlantica, Genentech/Roche, Gilead Sciences, GlaxoSmithKline Services, Ichnos Sciences S.A., InDex Pharmaceuticals, Janssen Pharmaceuticals, Lilly, Narrow River Mgmt, Pfizer, Prometheus Laboratories, Reistone, Shire, Takeda, and Techlab Inc. N.C. has served as a consultant for Arena Pharmaceuticals and Takeda. D.C. has served on the speaker bureau for Janssen Pharmacueticals.

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