Ustekinumab, Ozanimod Have Comparable Profiles for Ulcerative Colitis

Marla C. Dubinsky, MD

New research shows a lot of similarities in efficacy and safety for ozanimod and ustekinumab in treating patients with ulcerative colitis.

A team, led by Marla C. Dubinsky, Icahn School of Medicine at Mount Sinai, used a matching-adjusted indirect comparison to compare the efficacy and safery of ozanimod and ustekinumab in patients with moderately to severely active ulcerative colitis.

The Drugs

Ozanimod is the first oral spingosine 1-phospate receptor modulator that has garnered approval for adults with moderately to severely active ulcerative colitis. Ustekinumab is a human interleukin (IL)-12 and IL-23 antagonist that is also approved for patients with ulcerative colitis.

However, there has been no head-to-head randomized controlled trials comparing the 2 treatments.

In the study, presented during Digestive Disease Week (DDW) 2022 Annual Meeting in San Diego, the investigators weighted individual patient-level data from the True North trial of ozanimod to match patient populations based on aggregate data from the UNIFI study of ustekinumab.

They also matched baseline characteristics, including age, sex, total Mayo score, disease extent, and prior biologic use.

The team assessed clinical remission, clinical response, endoscopic improvement, and mucosal healing using the placebo arm as an anchor in both the induction and maintenance phases based on feasibility analysis and compared durable clinical remission during the maintenance periods.

Next, they compared efficacy outcomes in the overall population, as well as in the subgroups of biologic-naïve and biologic-experienced patients.

Finally, the investigators compared safety outcomes in the overally population, including serious treatment-emergent adverse events (TEAEs), infectious adverse events, and serious infectious adverse events.

The Data

Prior to matching, patients from the ozanimod trial had a higher likelihood of left-sided colitis (62.5% vs 52.5%; P <0.01) and a lower proportion with prior biologic use (32.9% vs 54.3%; P <0.001) compared to the ustekinumab trial.

However, following matching, the adjusted baseline characteristics were balanced.

In the induction phase, there was a comparable efficacy between the 2 groups in the overall population and the biologic-naïve subgroup.

For biologic-experienced patients, treatment with ozanimod had comparable clinical remissiom, clinical response, and mucosal healing compared with ustekinumab.

During the maintenance period, the efficacy was comparable between the 2 treatments in the overall population, as well as both subgroups.

The safety profile was also comparable between the 2 drugs, but ozanimod had significantly lower rates of infectious adverse events (risk difference vs UST, −24.9%; P <0.001) during maintenance.

“The MAIC results showed a comparable benefit-risk profile for OZA vs UST overall and in the biologic-naïve and biologic-experienced subgroups,” the authors wrote. “Safety was comparable, with more favorable infection AE rates with OZA.”

The study, “Su1500: COMPARATIVE EFFICACY AND SAFETY OF OZANIMOD AND USTEKINUMAB IN PATIENTS WITH MODERATELY TO SEVERELY ACTIVE ULCERATIVE COLITIS,” was published online by DDW 2022.