Ozanimod Expands Treatment Options for Ulcerative Colitis in Adult Patients
As a review article published last year in the journal Drugs suggests, ozanimod is an effective and well-tolerated medication for adult patients with moderate to severe ulcerative colitis (UC), both in the initial phase of treatment and in the maintenance phase after achieving remission.
Indications
The oral sphingosine-1-phosphate receptor (S1PR) modulator ozanimod was originally approved for the treatment of relapsing-remitting multiple sclerosis (RRMS). It is now also indicated in the EU for the treatment of adult patients with moderate to severe active ulcerative colitis who have not achieved adequate response to conventional or biological therapy, have lost response to such therapy, or were intolerant to it.
Mechanism of Action
Ozanimod is a potent S1PR modulator with high affinity for the S1PR1 and S1PR5 receptors. The exact mechanism by which ozanimod achieves its therapeutic effect in ulcerative colitis is still unknown. However, it is hypothesized that it may be related to the induced reduction of lymphocyte migration to the gut. A greater reduction is observed in lymphocytes involved in the acquired (adaptive) immune response, whereas the innate immune response is minimally affected.
Pharmacodynamic Properties
In randomized controlled trials, ozanimod reduced levels of inflammatory bowel markers – fecal calprotectin and fecal lactoferrin – during the induction phase of ulcerative colitis treatment, and this reduction persisted into the maintenance phase. In the phase III True North study, ozanimod reduced levels of circulating neutrophils and the CPa9 fragment of calprotectin degradation induced by human neutrophil elastase in both the induction and maintenance phases, indicating markers of increased systemic inflammation.
Given that S1P signaling affects cardiac function, S1PR modulators can impact cardiovascular function and heart rate. Ozanimod can induce a transient decrease in heart rate but does not lead to QTc interval prolongation or clinically significant bradycardia.
Clinical Efficacy and Safety
The clinical efficacy and safety of ozanimod in the treatment of moderate to severe ulcerative colitis in adults have been demonstrated in 2 randomized double-blind placebo-controlled phase III studies. These included the 52-week phase III True North trial involving 1012 patients and the 32-week phase II Touchstone study with 197 patients. Both had induction and maintenance phases followed by an open-label extension.
In the True North study, ozanimod significantly increased the proportion of patients achieving clinical remission compared to placebo at the end of both the induction and maintenance phases. Similar results were observed in the Touchstone study. Data from the long-term open-label extension of both studies indicate that the efficacy of ozanimod persists up to 142 and 200 weeks, respectively.
Ozanimod was generally well tolerated in these studies, with a tolerability profile similar in both the induction and maintenance phases of treatment. Adverse events of special interest, including deviations in liver function tests, changes in lymphocyte counts, infections, and events related to cardiac function, had a generally low incidence and were manageable and transient. The proportion of patients discontinuing ozanimod due to adverse events was minimal.
Ozanimod in Practice
Ozanimod is administered orally once daily with or without food, with dose titration over 7 days from 0.23 to 0.92 mg/day. Before starting therapy and during its administration, it is necessary to monitor complete blood count, cardiac and liver functions, vaccination status, and concomitant medications.
Contraindications for ozanimod include immunodeficiency, severe hepatic impairment, second-degree type II and third-degree atrioventricular blocks, or sick-sinus syndrome, unless the patient has a functional pacemaker.
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Sources:
1. Paik J. Ozanimod: a review in ulcerative colitis. Drugs 2022 Aug; 82 (12): 1303−1313, doi: 10.1007/s40265-022-01762-8.
2. Harris S., Wu C., Li Y. et al. The effect of ozanimod on circulating neutrophils: results from the True North study of patients with moderately to severely active ulcerative colitis. DDW 2022: Tu1466. Available at: https://eposters.ddw.org/ddw/2022/ddw-2022/355630/sarah.harris.the.effect.of.ozanimod.on.circulating.neutrophils.results.from.html
3. SPC Zeposia. Available at: www.ema.europa.eu/en/documents/product-information/zeposia-epar-product-information_cs.pdf
You can find the abbreviated product information here.
Commercial communication by Bristol-Myers Squibb spol. s r.o
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