Ustekinumab Biosimilar Switch Holds Up in Crohn Disease

Six months after Italian clinicians began switching clinically stable patients with Crohn disease from reference ustekinumab to biosimilars, the results look almost indistinguishable from staying the course, according to a study published in Clinical Gastroenterology and Hepatology.¹

Across 18 centers and 462 patients, clinical success held steady whether patients switched or continued on the originator, adding some of the most convincing real-world evidence yet that a procurement-driven, nonmedical switch does not erode disease control.

A prospective Italian cohort found procurement-driven switching from reference ustekinumab to biosimilars preserved remission and safety in Crohn disease over 6 months. | Image credit: eddows - stock.adobe.com

Why Switching Data Were Needed

The first US biosimilar competitor for reference ustekinumab (Stelara; Johnson & Johnson) launched on January 1, 2025 (ustekinumab-auub, Wezlana; Amgen). The approval rested on a phase 3 trial of 563 adults with moderate to severe plaque psoriasis that found no clinically meaningful difference in Psoriasis Area and Severity Index response between the biosimilar and the originator.² Like most of its competitors, ustekinumab-auub was approved on psoriasis trial data extrapolated to inflammatory bowel disease. That left gastroenterologists with little dedicated evidence on how a Crohn disease population, specifically, would fare after a payer- or procurement-driven switch rather than a voluntary one.

The investigators behind the USBIOS study, run under the Italian Group for the Study of Inflammatory Bowel Disease, set out to close that gap with controlled, prospective, real-world data rather than relying on inference from the trials that originally supported biosimilar approval.¹

Study Design and Patient Population

The prospective observational cohort, conducted across 18 Italian centers, enrolled adults with Crohn disease in clinical remission, defined as a Harvey-Bradshaw Index below 5, who had been steroid-free for at least 8 months on reference ustekinumab. Clinicians either carried out a procurement-driven switch to 1 of 3 approved biosimilars or continued patients on the reference product. Of 462 patients, 337 switched and 125 remained on the originator. Only 4 patients, or 0.9% of the cohort, were on every-4-week dosing, a detail the investigators flagged as worth tracking with longer follow-up.

The primary end point, expanded clinical success, required that patients remain in remission without systemic corticosteroids, without discontinuing their anti-interleukin-12/23 therapy, and without an inflammatory bowel disease-related hospitalization or intestinal surgery.

Switching Held Its Own Against Continued Reference Treatment

Expanded clinical success occurred in 306 of 332 evaluable switched patients (92.2%) and 114 of 123 continued-reference patients (92.7%), a risk difference of just –0.5 percentage points (95% CI, –5.9 to 4.9) that met the study's prespecified noninferiority margin of –15%. The result held up under a stricter, protocol-defined 3-component composite end point and after propensity-score weighting to adjust for baseline differences between the groups.

Biosimilar persistence was high, at 93.7%, and switch-back to the reference product occurred in just 1.2% of patients. Only 2 adverse events were reported in the switched group over the 6-month follow-up. "In clinically stable CD, the observed 6-month effectiveness and safety after procurement-driven ustekinumab biosimilar switching were similar to continued reference treatment," the researchers wrote.

Limitations and What It Means for Formulary Strategy

The authors acknowledged that 6 months is a relatively short window to judge durability, particularly for the small subset of patients dosed every 4 weeks, and called for longer-term studies to confirm that the noninferiority signal holds as more patients move onto less-studied dosing intervals.

Payers and health systems weighing procurement decisions on ustekinumab now have real-world evidence behind a biosimilar class that has already begun reshaping formulary strategy in inflammatory bowel disease. With persistence above 93% and switch-back under 2%, the Italian data suggest mandated, nonmedical switches can be executed with minimal disruption to patients already in remission, supporting continued efforts to steer utilization toward lower-cost options without added monitoring burden.

References

1. Ribaldone DG, Tribocco E, Scaldaferri F, et al. Clinical outcomes after ustekinumab biosimilar switching in Crohn's disease: the USBIOS-Italian Group for the Study of Inflammatory Bowel Disease study. Clin Gastroenterol Hepatol. Published online August 27, 2026. doi:10.1016/j.cgh.2026.08.014

2. Welcome Wezlana: the first Stelara biosimilar to launch in the US. The Center for Biosimilars^®. Accessed October 2026. https://www.centerforbiosimilars.com/view/welcome-wezlana-the-first-stelara-biosimilar-to-launch-in-the-us