Zeposia approved for treatment of moderately to severely active ulcerative colitis

Celgene/Bristol-Myers Squibb has received Health Canada approval for a new therapeutic indication for Zeposia (ozanimod capsules). Zeposia was originally indicated for use in the treatment of relapsing remitting multiple sclerosis. It is now also approved for use in the treatment of moderately to severely active ulcerative colitis in adults with an inadequate response, loss of response or intolerance to conventional therapy or a biologic agent.1 In patients ≥ 65 years of age with moderately to severely active ulcerative colitis, the drug is indicated only for induction treatment (not maintenance treatment), as efficacy in clinical trials (compared with placebo) was only observed in the induction phase.1 Read: Ibsrela: new treatment for irritable bowel syndrome with constipation Mechanism of action The exact mechanism of action of ozanimod in ulcerative colitis is unknown. It binds to sphingosine 1-phosphate (S1P) receptors, preventing lymphocyte exit into peripheral blood and reducing lymphocyte migration into the intestine and central nervous system.2 Dosage The recommended dosage of ozanimod is the same for both relapsing remitting multiple sclerosis and ulcerative colitis. Patients start with the seven-day initiation pack: 0.23 mg once daily (days 1–4), 0.46 mg once daily (days 5–7), and then continue with 0.92 mg once daily (day 8 and onwards). The capsules can be administered with or without food, but should be swallowed whole.1 Efficacy In a 10-week induction trial in adults with moderately to severely active ulcerative colitis, significantly more patients achieved clinical remission at week 10 with ozanimod than with placebo. In a maintenance trial involving patients who had a clinical response after 10 weeks of induction therapy, significantly more patients who received ozanimod (compared with placebo) were in clinical remission after an additional 42 weeks of treatment. Among patients who achieved clinical remission during the induction phase, 52% of those who continued ozanimod in the maintenance phase remained in clinical remission, compared to 29% of those who were re-randomized to placebo.2 Read: Test what you know about 'prehabilitation' before gastric cancer surgery Adverse effects Abnormal liver function tests, upper respiratory infections and headache are the most common adverse effects of ozanimod in patients with ulcerative colitis, occurring in ≥ 4% of patients in clinical trials.2 When starting ozanimod treatment, transient reductions in heart rate and atrioventricular conduction delays may occur. Other adverse effects reported in clinical trials for ulcerative colitis include hypertension, dose-dependent reductions in FEV1 (forced expiratory volume in 1 second) and FVC (forced vital capacity), herpes zoster, macular edema, peripheral edema and malignancies (e.g., melanoma).2 S1P receptor modulators can increase the risk of infection (e.g., herpes simplex encephalitis, varicella zoster meningitis). Progressive multifocal leukoencephalopathy and fatal cryptococcal meningitis have also occurred. It is uncertain whether S1P receptor modulators can increase the risk of COVID-19 or its immunological complications.2 Contraindications Ozanimod is contraindicated in several situations, including patients with clinically significant cardiovascular diseases, type II second- or third-degree atrioventricular block, and females of child-bearing age who are not using contraception.3 Drug interactions Coadministration with strong CYP2C8 inhibitors (e.g., gemfibrozil) or inducers (e.g., rifampin) is not recommended. MAO inhibitors are contraindicated during ozanimod therapy and within 14 days after stopping the drug. Concurrent use of serotonergic drugs (including opioids) or noradrenergic drugs is not recommended as this could result in hypertensive crisis. Use with drugs that prolong the QT interval could result in additive effects and arrhythmias (e.g., torsades de pointes). Concurrent use with immunosuppressants requires caution during ozanimod treatment and for four weeks after stopping the drug due to the risk of additive immunosuppressive effects.1,2 Live attenuated vaccines should not be administered for at least one month before starting ozanimod treatment and for three months after stopping the drug. Vaccinations may also be less effective during ozanimod therapy and for up to three months after discontinuation of treatment.1,2 Read: Which immunizations should patients with inflammatory bowel disease receive? Patients should be advised to avoid foods containing a large amount of tyramine (> 150 mg) while taking ozanimod due to the risk of severe hypertension.1,2 Summary Ozanimod is the first S1P modulator to be approved for ulcerative colitis, providing a new therapeutic option for patients with moderate to severe disease. It has the advantage of once-daily oral administration,3 but is expensive and has not been directly compared with other drugs for ulcerative colitis.2 Clinical trials of ozanimod in Crohn’s disease are also underway.2 References 1. Celgene Inc. Zeposia (ozanimod capsules) product monograph. Saint-Laurent, QC; April 7, 2022. https://pdf.hres.ca/dpd_pm/00065373.PDF (accessed April 19, 2022). 2. Anon. Ozanimod (Zeposia) for ulcerative colitis. Med Lett Drugs Ther 2021;63:147-51. 3. Aoun R, Hanauer S. A critical review of ozanimod for the treatment of adults with moderately to severely active ulcerative colitis, Exp Rev Gastroenterol Hepatol 2022; published online April 11, 2022, DOI: 10.1080/17474124.2022.2065258.

Zeposia approved for treatment of moderately to severely active ulcerative colitis

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