Ulcerative Colitis Study: Ozanimod Tops Adalimumab, Equals Vedolizumab

Laird Harrison

November 02, 2021

LAS VEGAS — In a comparison of data from clinical trials for ulcerative colitis, ozanimod (Zeposia) appeared to be more useful than adalimumab (Humira) and as useful as vedolizumab (Entyvio).

The US Food and Drug Administration (FDA) approved ozanimod for ulcerative colitis in May of this year, and clinicians are trying to figure out where it fits into the armamentarium, said Marla Dubinsky, MD, professor of pediatrics and medicine in the Division of Pediatric Gastroenterology at Icahn School of Medicine at Mount Sinai, in New York City.

"It's an extremely heterogeneous disease," Dubinsky told Medscape Medical News. "A lot of these indirect comparisons are being done, because these therapies are coming out so quickly."

No clinical trials have compared either ozanimod to adalimumab or ozanimod to vedolizumab head to head, so Dubinsky and colleagues pitted the drugs against each other by matching data from individual patients from the True North trial of ozanimod to published data from the ULTRA 1 and 2 trials of adalimumab and the GEMINI 1 trial of vedolizumab.

She presented the findings here at the American College of Gastroenterology (ACG) 2021 Annual Scientific Meeting.

From the 1990s until 2014, physicians relied heavily on tumor necrosis factor (TNF) inhibitors, such as adalimumab, to treat ulcerative colitis, Dubinsky said. Although often effective, these drugs can increase patients' vulnerability to infections and malignancies.

Approved by the FDA in 2014, vedolizumab works differently: it blocks α4β7 integrin. "The safety profile was extremely favorable," Dubinsky said. "That was a revolution, in my opinion." Still, vedolizumab isn't always effective, especially for patients who have already received TNF inhibitors without success.

As reported by Medscape Medical News, ozanimod works by yet another mechanism: sphingosine l-phosphate receptor modulation.

How Does Ozanimod Measure Up?

To see how ozanimod stacks up to the two older drugs, Dubinsky and colleagues weighted the data from True North to match the patient populations in the other trials by age, sex, baseline total Mayo score, disease extent, and prior anti-TNF treatment.

They calculated the odds that ozanimod would produce better clinical and endoscopic responses or be associated with more serious or infectious adverse events in comparison with each of the other drugs. The comparisons included both the induction and maintenance phases of the trials.

The researchers compared ozanimod to adalimumab for patients who were anti-TNF naive. They found that the patients who took ozanimod were more likely to experience a clinical response than those who took adalimumab (odds ratio [OR], 1.68; 95% CI, 1.03 – 2.74). The patients who took ozanimod were also more likely to have endoscopic improvement (OR, 2.73; 95% CI, 1.44 – 5.17).

They found that the patients who had received a TNF inhibitor were also more likely to experience a clinical response with ozanimod than with adalimumab (OR, 2.53; 95% CI, 1.13 – 5.67).

In both the induction and the maintenance phases, the other differences in efficacy between ozanimod and adalimumab did not reach statistical significance.

As for safety, in the induction phases of the trials, the researchers found that 11.3% of patients who received ozanimod had infections, compared to 20.2% of those taking adalimumab, which was statistically significant (P < .01). Other differences in safety were not statistically significant.

With regard to vedolizumab, Dubinsky and colleagues found no statistically significant differences between it and ozanimod in the induction phases.

In the maintenance phases, among patients who were anti-TNF naive, the odds of clinical response were lower with ozanimod than with vedolizumab (OR, 0.40; 95% CI, 0.21 – 0.76). The odds of endoscopic improvement were very nearly lower (OR, 0.52; 95% CI, 0.27 – 1.01). The researchers attributed these findings to a higher placebo response in the True North trial (the ozanimod trial) than in GEMINI 1 (the vedolizumab trial).

There were no other significant differences in efficacy between ozanimod and vedolizumab, either in the cohort that had received a TNF inhibitor or in the cohort that had not.

As for safety, there were also no statistically significant differences between vedolizumab and ozanimod in the induction phases. During the maintenance phases, 71.3% of patients who received vedolizumab had infections, compared to 25.0% in the matched cohort of patients who received ozanimod, which was a statistically significant difference (P < .001). The other differences in this phase were not significant.

Dubinsky acknowledged that the results were not as reliable as would have been the case in a prospective, head-to-head comparison, because the researchers could not be sure that they had fully adjusted for the differences in the populations and the designs of the studies.

"In TNF-inhibitor–naive patients, I could use vedolizumab or ozanimod," Dubinsky said. But these are not the only options, she said. She said that "in TNF failure, I would use ustekinumab or even tofacitinib." Ustekinumab (Stelara) is a human interleukin-12 and -23 antagonist; tofacitinib (Xeljanz) is a Janus kinase inhibitor.

The study's limitations are significant, said session moderator Jonathan Leighton, MD, a professor of medicine at the Mayo Clinic in Phoenix, Arizona, "but it certainly shows that ozanimod had a positive profile compared to adalimumab and has overall comparable benefits with vedolizumab," he told Medscape Medical News.

Leighton added that someday researchers may find biomarkers that will identify the best drug for each patient. In the meantime, clinicians are often left choosing therapies on the basis of such factors as which route of administration the patients prefer, he said. Vedolizumab is given by intravenous infusion, ozanimod is taken orally, and adalimumab is given by subcutaneous injection.

The study was funded by Bristol-Myers Squibb. Leighton has financial relationships with Olympus and Pfizer. Dubinsky has relationships with all or most of the companies that make drugs for inflammatory bowel disease.

American College of Gastroenterology (ACG) 2021 Annual Scientific Meeting: Abstract 21. Presented October 26, 2021.

Laird Harrison writes about science, health, and culture. His work has appeared in magazines, newspapers, on public radio, and on websites. He is at work on a novel about alternate realities in physics. Harrison teaches writing at the Writers Grotto. Visit him at lairdharrison.com or follow him on Twitter: @LairdH.

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