Biologic medications have become the standard of care for moderate to severe inflammatory bowel disease (IBD), helping more people reach remission and control disease progression than ever before. But the current crop of available drugs still may not work for everyone, or they may stop working for some people over time. The good news is that more advanced therapies for Crohn’s disease and ulcerative colitis (UC) are continuing to emerge.
“We have already gone from a handful of treatment options to more than a dozen, with several new drug classes close behind. I think the bigger change will be learning which drug fits which patient, so people spend less time cycling through medicines that don’t work for them,” says John Appiah, MD, a gastroenterologist with Geisinger in Wilkes-Barre, Pennsylvania.
Here’s a look at the options on the horizon that you may be able to ask your gastroenterologist about today.
1. TL1A Inhibitors
New drugs in development include TL1A inhibitors, which block the tumor necrosis factor-like ligand 1A (TL1A) protein, a driver of chronic gut inflammation and scarring.
Scarring is what leads to strictures, the narrowed sections of intestine that can lead to dangerous blockages in the gastrointestinal (GI) tract, which are more common in Crohn’s disease. “None of our current medications reliably prevent it. TL1A inhibitors are promising because they address [inflammation and scarring] at once,” says Alan Moss, MD, the chief scientific officer for the Crohn’s & Colitis Foundation.
Three TL1A inhibitors — tulisokibart, afimkibart, and duvakitug — are currently in phase 3 clinical trials for Crohn’s disease and UC, with results expected by 2027. The U.S. Food and Drug Administration (FDA) will weigh in once drug companies complete their applications; any approved drugs would become available soon after. “They may eventually be particularly useful for patients who have not responded to other therapies, and possibly for stricturing Crohn’s disease,” Dr. Appiah says.
2. Microbiome-Based Therapies
There is strong evidence the gut’s microbiome, its collection of bacteria and other microbes, plays a role in the development and progression of IBD. And researchers are continuing to find ways to apply what they’ve learned toward developing new treatments, such as fecal microbiota transplantation (FMT). The therapy involves transferring a medically processed stool sample from the gut of a healthy person to the gut of a person with IBD. Most often, the transplant is done using oral capsules or an enema.
The idea behind FMT is that good gut bacteria from the healthy stool sample can help spur the growth of good bacteria in an IBD gut. And indeed, some studies have shown that FMT may help some people with mild to moderate UC reach remission. For now, there’s not much research on using FMT in Crohn’s disease, so scientists haven’t been able to draw conclusions yet.
Experts say that more studies are needed before FMT can become a standard treatment for UC, however. ”The evidence is still limited,” says Appiah.
That said, both Appiah and Dr. Moss believe there’s a place for FMT in the future UC treatment arsenal. “My view is that microbiome modulation may become an add-on to medications, helping patients maintain remission, rather than [as a] stand-alone treatment,” Moss says, adding that “we’ll also need better ways to predict which patients are most likely to respond.”
3. GLP-1 Medications
Glucagon-like peptide-1 receptor agonists (GLP-1s) like semaglutide (Ozempic, Rybelsus, Wegovy) and tirzepatide (Mounjaro, Zepbound) have become common treatments for diabetes and obesity. And whether they’ll come to play a dedicated role in treating IBD “is one of the most intriguing questions in our field right now. But it’s still early,” Moss says.
What we do know: GLP-1s have been shown to exert an anti-inflammatory effect in laboratory models of IBD. And recent findings suggest that GLP-1 use for diabetes or obesity among people with an IBD is tied to potential added GI benefits in people with IBD.
Clinical trials are needed to confirm these preliminary findings and more rigorously test whether GLP-1s are actually a safe and effective way to control IBD. But in the meantime, the meds can still be useful for managing diabetes or obesity, which may both make IBD harder to control.
“I see [GLP-1s] as helping the whole patient rather than replacing IBD medicines,” says Appiah.
4. Stem Cell Therapies
Stem cell therapy, commonly known as bone marrow transplantation, has been shown to reduce disease activity in some people with Crohn’s disease. Autologous stem cell therapy transplants healthy stem cells from a person’s own bone marrow into their bloodstream to reduce inflammation.
“It essentially ‘resets’ the immune system, which can help some people with severe, treatment-resistant Crohn’s,” Moss says. It’s an experimental treatment, however, that can come with serious risks, including severe infection, kidney failure, and liver toxicity.
Will stem cell therapy ever be a cure for Crohn’s or UC? “I am hopeful,” says Appiah. But we’re likely many years — and many clinical trials — away from that potential reality. “A more realistic goal for the next decade [are drug-based therapies that help people with IBD achieve] long-lasting, deep remission, with bowel healing and a[n improved] quality of life,” he says.
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