Ustekinumab Shows Sustained Symptomatic, Corticosteroid-Free Remission in Adults with Moderately to Severely Active Ulcerative Colitis

Ustekinumab (Stelara; Johnson and Johnson) produced sustained efficacy and safety over 4 years in adult patients with moderately to severely active ulcerative colitis (UC), according to final data from the long-term extension (LTE) phase 3 UNIFI trial. In the trial, randomized patients with UC who received corticosteroids at maintenance baseline were able to eliminate the use of corticosteroids by week 200. These results were presented at the United European Gastroenterology Week 2022 congress.

Among 348 patients who achieved a clinical response with ustekinumab during induction and who were randomized to ustekinumab 90 mg every 8 weeks or every 12 weeks at baseline of the maintenance study, 64.9% were in symptomatic remission after 44 weeks of maintenance. At week 200, this proportion of patients was 55.2%, with the majority not receiving corticosteroids.

Among 174 patients who received ustekinumab as their first biologic for UC, 71.8% of these patients were in symptomatic remission after 44 weeks of maintenance, and 67.2% were in remission at week 200.

“Stelara is a well-established therapy, and the final results of the UNIFI LTE study demonstrate sustained, long-term clinical benefit in moderately to severely active ulcerative colitis,” Jan Wehkamp, MD, vice president, Gastroenterology Disease area leader, Janssen Research & Development, LLC, said in a press release. “We hope this is welcome news for patients who are seeking long-term treatment options that may provide enduring relief from the debilitating symptoms of the disease.”

Ustekinumab is a human interleukin (IL)-12 and IL-23 antagonist approved in the United States for the treatment of patients 6 years of age and older with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy; patients 6 years of age and older with active psoriatic arthritis; patients 18 years of age and older with moderately to severely active Crohn disease; and patients 18 years of age and older with moderately to severely active UC.

UNIFI was designed to evaluate the safety and efficacy of ustekinumab induction and maintenance dosing for the treatment of moderately to severely active UC in adults who demonstrated an inadequate response to or were unable to tolerate conventional or biologic therapies. The induction study was at least 8 weeks for each participant, and those who achieved clinical response in the induction study were eligible for the maintenance study.

The maintenance study lasted 44 weeks, with the primary endpoint being clinical remission at week 44 among responders to a single intravenous (IV) ustekinumab infusion. Additionally, 523 responders to IV ustekinumab induction were randomized to subcutaneous maintenance therapy, and 284 patients who completed week 44 entered the LTE.

The randomized placebo cohort was discontinued after week 44 unblinding. The LTE of UNIFI followed eligible participants for an additional 3 years upon completion of the maintenance study.

Safety findings were similar among both the ustekinumab and placebo cohorts in the study. The investigators found that the ustekinumab group had 1647.4 patient-years (PYs) of follow-up compared with 301.7 PYs in the placebo group from maintenance week 0 through week 220. The numbers of events per 100 PYs of follow-up were 214.45 adverse events (AEs) in the ustekinumab group compared with 288.04 for placebo, serious AEs were 7.22 for the ustekinumab group compared with 10.61 for the placebo group, and serious infections were 2.00 for the ustekinumab group compared with 3.31 for the placebo group. There were no new safety signals observed.

“The final LTE results of the UNIFI study demonstrated that Stelara can be an effective long-term treatment option for patients living with moderately to severely active ulcerative colitis, including in patients who are biologic-naive,” said UNIFI presenting study author Waqqas Afif, MD, associate professor, Department of Medicine, Division of Experimental Medicine and Division of Gastroenterology at McGill University Health Centre in Montreal, Canada, in a press release. “Importantly, the vast majority of patients who achieved remission in the study were able to eliminate the use of steroids, which can cause significant side effects and are not a long-term treatment solution for the disease.”

REFERENCE

STELARA® (ustekinumab) Demonstrated Sustained Symptomatic and Corticosteroid-Free Remission Through Four Years in Adults with Moderately to Severely Active Ulcerative Colitis. Johnson and Johnson. October 10, 2022. Accessed October 11, 2022. https://www.jnj.com/stelara-ustekinumab-demonstrated-sustained-symptomatic-and-corticosteroid-free-remission-through-four-years-in-adults-with-moderately-to-severely-active-ulcerative-colitis