Comparing inflammatory bowel disease treatment options

March 26, 2024 - Last month, AbbVie sponsored several presentations and posters at the European Crohn's and Colitis Organization’s (ECCO) annual congress. Among these abstracts was the SEQUENCE study, which compared risankizumab and ustekinumab for treating inflammatory bowel disease (IBD).

Marla Dubinsky, MD, lead study investigator, sat down with PharmaNewsIntelligence to discuss the evolving IBD landscape, the sequence study, and future research directions.

Global IBD Rates

IBD is an umbrella term for a group of diseases that cause chronic or recurrent inflammation in the intestinal tract. The two most common types of IBD are ulcerative colitis (UC) and Crohn’s disease (CD).

“On average, about 1.2% of the population in the United States have been diagnosed with inflammatory bowel disease,” began Dubinsky.

Despite some rhetoric suggesting an increase in IBD rates, Dubinsky notes that the incidence has not increased significantly.

“The reason there's a feeling of an increase in prevalence is something called compound prevalence, which means people are living longer,” she explained. “At any given moment, more individuals are being managed for inflammatory bowel disease. For example, the incidences, which look at new cases over an annual rate, aren't increasing as much as the prevalence is increasing.”

Although global rates of new IBD have not changed overall, Dubinsky discussed two additional trends with PharmaNewsIntelligence. First, she explained that the rate of new diagnoses among younger and elderly patients has increased, while middle-aged patients' diagnosis rates have remained stable.

Secondly, she noted that “There is a globalization of inflammatory bowel disease, and we see emerging areas of the world that weren't having highly prevalent IBD population now having. Whether it's globalization, industrialization, westernization — however, the terminology we're using — there is indeed an increase in cases in parts of the world where we weren't even focused on.”

Dubinsky notes that the trends in IBD rates emphasize that we need more research on how the environment impacts the condition.

IBD Treatment Options

“We've had somewhat of an expansion of therapies for UC and CD,” Dubinsky emphasized.

There are many FDA-approved medications to manage IBD, including UC and CD. The medication used may depend on the specific type of IBD a patient has, their medical history, and other factors; however, all the medications aim to reduce gastrointestinal inflammation and promote intestinal healing.

According to New York University Langone Health, corticosteroids, 5-aminosalicylic acid medications, immunomodulators, and biologic therapies, such as anti-TNF agents and anti-integrin therapies, can manage IBD.

Providers may also use conjunctive medications such as antibiotics, antispasmodic agents, pain relievers, and supplements to manage disease symptoms.

“There is an incredible amount of choices, and each has its role,” Dubinsky explained. “We're beginning to see that with all these therapies and multiple classes, the problem will lie in choosing [the right] therapy and which one to choose first or sequence second.

SEQUENCE Study

One of the primary goals of the SEQUENCE study was to understand how providers should sequence treatment options for IBD, specifically when choosing between risankizumab and ustekinumab.

The phase 3 multicenter, randomized clinical trial randomized patients to receive one of the two drugs. Although in clinical practices, many providers will escalate Ustekinumab every four weeks until they reach an effective or the maximum dose, this study required that neither drug be escalated.

“There were two co-primary endpoints that had to be met. One is a non-inferiority endpoint, which was clinical remission at week 24. That meant that risankizumab could not be less effective within a 10% margin to ustekinumab. That was met,” Dubinsky explained. “The other primary endpoint, which was really important, is endoscopic remission at week 48,” added Dubinsky.

She noted that the SEQUENCE study was the first time IBD drugs have been held to the endoscopic remission standard. Endoscopic remission is a relatively high threshold to set for IBD drug efficacy.

Early on, the bar for IBD treatments is whether or not a patient feels better. Then, down the line, the question was how much better they felt. Eventually, biomarkers for improvement emerged; however, Dubinski claims that endoscopic remission exceeds these standards.

She revealed that for CD, the trial showed that patients who have failed anti-TNF therapy are more effectively treated with risankizumab than ustekinumab.

“The data showed that there was essentially a twofold increase rate of endo remission at week 48 with risankizumab versus ustekinumab.”

Based on the results from the study, she and the researchers postulate that risankizumab is a more effective treatment than ustekinumab and should be sequenced first for patients treated for IBD.

“Some of us are under the impression that the reason why risankizumab is superior is because we finally got the dose right for CD We had to dose a drug for an endoscopic outcome in the registration trials. Until risankizumab, no other drug registration trial had to meet an endoscopic outcome to get approved,” added Dubinsky.

Future Research Directions

In her discussion with PharmaNewsIntelligence, Dubinsky explained that there is an arsenal of treatments for IBD; the challenge is determining which medication to initiate and when.

“There are many different therapies, and we are using just ‘did they fail something’ as a way to make a choice, which is what SEQUENCE was about,” she said. “But the future is about how we choose the right one first because we know that the first therapy is most important.”

She notes that many factors may be considered in the future, including a family history of other inflammatory conditions and personal comorbidities.

Additionally, Dubinsky points out that future studies should continue to consider the impacts of combination therapy and how to optimize combinations based on the patient.

“We've got incredible drugs. So the studies that need to be done are more combination and sequencing studies, so we know when to add what drug, who needs both on day one and understand precision medicine a bit more.”

“There's a role for all of our drugs, and we just need to be able to understand the utilization and the order,” she concluded.