番茄社区

Ulcerative colitis relapses in patients with moderate-to-severe disease were seen as early as 8 weeks among responders who stopped ozanimod (Zeposia) after induction therapy, a post-hoc analysis of the phase III True North study found.

Through 52 weeks, 86.1% of those who continued onto maintenance treatment with the sphingosine 1-phosphate (S1P) receptor modulator were without relapse, as compared with 62.6% of those re-randomized to placebo after the 10-week induction phase (P<0.0001), reported Bruce Sands, MD, MS, of the Icahn School of Medicine at Mount Sinai in New York City.

And a significant separation was seen between the two arms as early as 8 weeks into the maintenance period (96.1% vs 90.6%, respectively), he said during his presentation at the American College of Gastroenterology annual meeting.

"These data show that ozanimod maintains disease control even in the event of temporary discontinuation, at least for a period of time," Sands said. "Disease activity at the start of maintenance did influence subsequent rates of disease relapse."

Non-relapse rates at 52 weeks were higher among those starting in clinical remission after induction compared with those only in clinical response for both the ozanimod group (90.9% vs 83.4%) and the placebo group (67.9% vs 59.7%).

"A short duration stop of ozanimod and then re-initiation was able to maintain remission. This is consistent with my own practice with ozanimod for ulcerative colitis," Miguel Regueiro, MD, of the Cleveland Clinic in Ohio, told 番茄社区. "That is, that it is effective at maintaining remission and even a brief 'pause' in therapy was effective if restarted."

Ozanimod was approved by the FDA for the treatment of moderate-to-severe ulcerative colitis in May 2021 based on data from True North.

Another analysis of True North showed symptom relief and biomarker improvement with just 1 week of full-dose ozanimod.

However, a may be needed in clinical practice, and understanding the duration of response after discontinuation may help with clinical decision making, Sands and colleagues noted.

True North randomized patients to once-daily oral ozanimod 0.92 mg or placebo for 10 weeks of induction. Clinical responders to ozanimod were re-randomized to receive the same dose of ozanimod or placebo for up to 52 weeks of maintenance.

"There were two cohorts, the initial cohort was a blinded, randomized cohort with randomization occurring 2:1 drug to placebo, and the second cohort, cohort 2, was an open-label feeder study to which responders were fed into the maintenance phase of the study," Sands explained.

For their post-hoc analysis, Sands and colleagues examined data on 457 patients -- 79 who were in clinical remission at 10 weeks and switched from ozanimod to placebo, 82 in clinical remission who continued ozanimod, 148 in clinical response at 10 weeks who were switched from ozanimod to placebo, and 148 in clinical response who continued ozanimod.

Baseline characteristics were similar across groups. Mean age was 42-45, and 50-57% were men. Nearly all were previously on aminosalicylic acid, while 15-35% were on concomitant corticosteroids. Mean Mayo score was 6.1-6.9 (out of 9).

Those with clinical response at week 10 had numerically higher rates of severe disease and prior use of immunosuppressants than those in clinical remission.

Disease relapse was defined by an increase of at least 2 points in the partial Mayo score compared with week 10, with an absolute partial Mayo score of ≥4, and an endoscopic subscore of ≥2.

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