NEJM Phase 3 Study Shows Ustekinumab Helps People Suffering with Ulcerative Colitis

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The biologic drug ustekinumab effectively induced and maintained remission in patients with moderate to severe ulcerative colitis, according to a phase 3 study published in the prestigious New England Journal of Medicine (NEJM).

Dr. Maria T. Abreu, center, with Maria Alejandra Quintero, M.P.H., left, and Diana Morillo, C.C.R.P.

The FDA approved ustekinumab, marketed as Stelara, for the treatment of adult patients with moderately to severely active ulcerative colitis on October 21, based largely on the positive NEJM phase 3 findings.

The inflammatory bowel diseases ulcerative colitis and Crohn’s disease can be debilitating, and there are only a few treatment options to help those who are suffering, according to study co-author Maria T. Abreu, M.D., University of Miami Miller School of Medicine professor of medicine, microbiology and immunology, and director of the University of Miami Health System Crohn’s & Colitis Center.

“We have an even shorter menu of options that patients find acceptably safe for long-term treatment. That’s not to mention that the diseases carry their own consequences. In the case of ulcerative colitis, it is an increased risk of colon cancer. So, we’re always looking for improved therapies,” said Dr. Abreu, who received the 2019 Sherman Prize awarded by The Bruce and Cynthia Sherman Charitable Foundation to recognize outstanding achievements in the fight to overcome Crohn’s disease and ulcerative colitis.

A study group of global researchers analyzed treatment with ustekinumab versus placebo in 961 moderate to severe ulcerative colitis patients. The FDA has already approved Stelara as a treatment for Crohn’s disease, psoriasis and psoriatic arthritis.

Ustekinumab is promising as a potential ulcerative colitis treatment for several reasons, according to Dr. Abreu. It is different from many of the monoclonal antibodies doctors currently use to treat inflammatory bowel and other diseases because it is the least immunogenic—meaning it is rare for patients on ustekinumab to develop antibodies to the drug rendering it ineffective.

“It’s also safe. The safety data from the current study goes through week 44,” Dr. Abreu said. “But all that wouldn’t really be interesting if it wasn’t effective, which it is.”

Dr. Abreu said it is striking that about half of the patients in the study had previously been on other biologic agents to treat their ulcerative colitis. And 14% of the patients had been on both an anti-tumor necrosis factor (TNF) and vedolizumab, another class of biologic agents used to treat ulcerative colitis.

“In other words, they had already been on at least two different types of therapies that work in different ways and those didn’t work,” she said. “In our specialty, we know that’s a very refractory group of patients, and even they experienced benefit from ustekinumab.”

Dr. Abreu and colleagues found that more than 15% of patients receiving ustekinumab had clinical remission by week eight, compared with about 5% of patients who received placebo.

The NEJM study was notable in that it included endoscopic efficacy, as well as clinical efficacy.  The researchers reported that at week eight about 20% of patients in the ustekinumab group had both histologic and endoscopic healing, compared with 9% of those in placebo.

“That’s a high bar — probably the highest bar to success,” Dr. Abreu said. “And the ustekinumab demonstrated that it is achievable. I think that it may set a new standard for what drugs need to achieve with respect to treatment for ulcerative colitis.”

Dr. Abreu pointed out that ustekinumab is convenient for patients. The first dose is given intravenously and subsequent doses are given subcutaneously every eight weeks.

“There’s nothing else in our field that is dosed as infrequently as ustekinumab,” she said.

Questions remain about whether providers can use ustekinumab in the sickest ulcerative colitis patients — those who are hospitalized with severe disease. Researchers also need to pursue studies using ustekinumab earlier, as a first-line biologic for patients who have failed level 1 therapies, as well as others who have mild to moderate disease, according to Dr. Abreu.