FDA Approves Ustekinumab for Patients with Acute Ulcerative Colitis

The FDA has approved ustekinumab (Stelara, Janssen) for the treatment of adult patients with moderately to severely active ulcerative colitis (UC).

The approval is based on the pivotal phase 3 UNIFI clinical trial, which demonstrated that treatment with ustekinumab both induced and maintained clinical remission in a significantly greater proportion of adult patients with moderately to severely active UC compared with placebo.

Published in the New England Journal of Medicine, the pivotal trial included an initial induction study (UNIFI-I) in which patients received a single dose of ustekinumab 6 mg/kg intravenous (IV) infusion. It was followed 8 weeks later by a Maintenance study (UNIFI-M), in which patients received ustekinumab 90 mg subcutaneous (SC) injections every 8 weeks for 44 weeks.

In the induction study, 19% of patients receiving ustekinumab achieved clinical remission in 8 weeks and the drug therapy provided rapid relief of symptoms, as 58% of patients receiving ustekinumab experienced a clinical response at week 8.

In the maintenance study, 45% of patients receiving ustekinumab were in remission at 1 year. Ustekinumab also helped patients achieve clinical remission without the use of corticosteroids. At 1 year, 43% of patients treated with ustekinumab were in clinical remission and not receiving steroids.

UC is a serious, chronic, and progressive immune-mediated inflammatory disease of the large intestine, affecting approximately 910,000 people in the United States. Ustekinumab targets the interleukin (IL)-12 and IL-23 cytokines, which have been shown to play an important role in inflammatory and immune responses.

Ustekinumab is approved to improve the intestinal lining as assessed by a novel histologic-endoscopic mucosal improvement endpoint. In the induction study, 17% of patients receiving ustekinumab achieved histologic-endoscopic mucosal improvement at week 8. In the maintenance study, 44% of patients receiving ustekinumab achieved histologic-endoscopic mucosal improvement at 1 year.

Histologic-endoscopic mucosal improvement is a combined measure that assesses the improvement of the colon at the cellular level through histologic examination and through images observed during colonoscopy. The relationship of histologic-endoscopic mucosal improvement to long-term outcomes was not studied in the clinical trial.

Reference

• Janssen Announces U.S. FDA Approval of STELARA® (ustekinumab) for the Treatment of Adults with Moderately to Severely Active Ulcerative Colitis [press release]. Market Insider website. Published October 21, 2019. https://markets.businessinsider.com/news/stocks/janssen-announces-u-s-fda-approval-of-stelara-ustekinumab-for-the-treatment-of-adults-with-moderately-to-severely-active-ulcerative-colitis-1028614725. Accessed October 21, 2019.