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UNITI trials show Stelara effective induction, maintenance treatment for Crohn's
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Data from the UNITI-1 and UNITI-2 induction trials and the IM-UNITI maintenance trial have been collectively published in The New England Journal of Medicine.
Taken together, these trials show that Stelara (ustekinumab, Janssen) effectively induced clinical response and maintained remission in patients with moderate-to-severe active Crohn’s disease.
Based on these data, Stelara was recently approved by the FDA and the European Commission for the treatment of adults with moderate-to-severe active Crohn’s disease for whom previous therapies have failed. It is the first biologic for Crohn’s disease that targets interleukin (IL)-12 and IL-23 cytokines.
Edward V. Loftus, Jr.
“It’s great to have another drug available with a unique mechanism of action,” Edward V. Loftus, Jr., MD, professor of medicine in the division of gastroenterology and hepatology at the Mayo Clinic, Rochester, Minn., told Healio Gastroenterology.
“The two UNITI trials showed that ustekinumab is effective to induce response and remission in Crohn’s disease in both the anti–TNF-experienced and -naive populations,” he said. “The maintenance IM-UNITI trial showed that the response to ustekinumab could be maintained. Also, the rate of adverse events or serious adverse events was not significantly different from that of placebo.”
In the two induction trials, Loftus and colleagues randomly assigned patients to receive either 130 mg ustekinumab, about 6 mg/kg ustekinumab, or placebo in a single IV dose. UNITI-1 involved 741 patients with primary or secondary nonresponse to anti-TNFs or unacceptable side effects, while UNITI-2 involved 628 patients who failed conventional therapy or had unacceptable side effects.
Clinical response at week 6 — the primary endpoint — was achieved by significantly greater proportions of the treatment vs. placebo groups in both trials; in UNITI-1, 34.3% of the 130-mg group and 33.7% of the 6-mg/kg group vs. 21.5% of the placebo group (P .003 for both), and in UNITI-2, 51.7% and 55.5% vs. 28.7% (P < .001 for both).
In the IM-UNITI maintenance trial, Loftus and colleagues randomly assigned 397 of the induction trial responders to receive 90 mg subcutaneous maintenance injections every 8 or 12 weeks, or placebo. Significantly greater proportions of both dose groups were in remission at 44 weeks, which served as the primary endpoint for this trial. At this time point, 53.1% of the 8-week dose group and 48.8% of the 12-week dose group were in remission vs. 35.9% of the placebo group (P = .005 and P = .04, respectively).
Comparable rates of overall adverse events, serious adverse events, and adverse events within an hour after infusion occurred across induction groups, and adverse events were comparable between maintenance and placebo groups with “no apparent relationship between dose and safety,” the researchers wrote. “The adverse events observed in these trials are consistent with 5 years of cumulative data acquired for patients with psoriasis ... and 2 years of safety data for patients with psoriatic arthritis. The rates of antidrug antibodies were low, as measured with the use of a drug-tolerant assay.” – by Adam Leitenberger
Disclosures: Loftus reports receiving personal fees from Janssen, Takeda, AbbVie, UCB Pharma, Genentech, Celgene, Amgen, Bristol-Myers Squibb, Eli Lilly, Mesoblast, Theradiag, Sun Pharma, and Seres Therapeutics and grant support from Janssen, Takeda, AbbVie, UCB Pharma, Genentech, Amgen, Bristol-Myers Squibb, Pfizer, Receptos, Gilead Sciences, and Robarts Clinical Trials. Please see the full study for a list of all other researchers’ relevant financial disclosures.
Perspective
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Adam Cheifetz, MD
Crohn's disease is a disorder that affects approximately 1 million people in the United State alone. It is a complex disease to treat and can have a major impact on patients' quality of life. Though we have several medications approved to treat Crohn's disease, not all therapies work for every patient and many patients often lose response to these therapies over time.
The FDA recently approved ustekinumab for induction and maintenance of remission in patients with moderate-to-severe Crohn's disease. This is an important step in treating Crohn's disease, as it has a different mechanism of action (anti-IL12/23) and may be particularly effective in those patients who are primary nonresponders to anti-TNF therapies or those who lost response to anti-TNF (with good anti-TNF drug concentrations).
The safety profile looks good based on long-term studies of patients with psoriasis for which ustekinumab was approved in 2009. The safety appears similar in Crohn's disease, though the dose we will be using is higher that that approved for psoriasis, so we await longer term follow up in Crohn's patients.
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