In a shift in standard practice, leading gastroenterologists are recommending doctors start Crohn’s disease patients on the most powerful drugs first—rather than wait—arguing that first trying cheaper, older medications wastes time while their intestines deteriorate.
The new American Gastroenterological Association (AGA) clinical guidelines allow patients with moderate to severe Crohn’s disease to bypass conventional therapies such as steroids and jump directly to advanced treatments, including biologics.
Why the Change?
Conventional first-line therapies, such as corticosteroids to reduce inflammation and immunomodulators, offer lower side-effect risk and are less costly. However, they rarely heal the inner lining of the digestive tract, meaning the disease could continue to damage tissue and progress even if patients experience remission.
In other words, corticosteroids and immunomodulators may only offer symptom relief while inflammation remains high and ulcers unaffected. Crohn’s disease is one type of inflammatory bowel disease (IBD) that can cause ulcers anywhere along the digestive tract—from the mouth to the anus.
“Continued inflammation can promote structural damage and potentially increase the risk of needing downstream surgical intervention and/or hospitalization,” Dr. Frank I. Scott, an expert in inflammatory bowel disease and chairman of the guideline panel, told The Epoch Times.
Patients receiving conventional treatment often need advanced therapies, Scott said, adding that delaying them can come at a cost.
What Are Advanced Therapies
Advanced therapy includes biologic drugs—such as infliximab, adalimumab, ustekinumab, risankizumab, mirikizumab, and guselkumab—that target and block inflammatory proteins. It also includes upadacitinib, an immunomodulator that reduces inflammation by inhibiting enzymes involved in the development of IBD.
Biologic drugs are injected or infused drugs that quiet the overactive immune system in IBD by blocking immune signals that trigger inflammation and attack healthy tissue.
The first biologic treatment for Crohn’s disease was approved in the early 2000s. Since then, a better understanding of immune pathways involved in inflammation has led to other classes of advanced therapies. Five novel drugs for moderate to severe Crohn’s have been approved since the AGA published the last set of treatment guidelines in 2021.
A 2024 study in Lancet Gastroenterology & Hepatology found that infliximab combined with an immunomodulator was associated with better outcomes at one year in patients newly diagnosed with Crohn’s disease. A meta-analysis published in Inflammatory Bowel Diseases revealed that early biologic treatment was associated with lower surgical rates.
A separate meta-analysis of advanced treatments, published in September in Inflammatory Bowel Diseases, showed a significant positive effect on achieving remission when biologics were used alongside immunomodulators.
The new guidelines do not recommend for or against using immunomodulators in combination with advanced therapies for moderate-to-severe cases. However, they do suggest taking patients off immunomodulators if they’ve achieved remission with a combination of advanced therapy and immunomodulator drugs after six months or longer.
The guidelines also suggest patients should remain on the advanced therapy drugs indefinitely. “For those with moderate to severe disease, lifelong medical therapy will likely be indicated. Each of these treatment decisions should, of course, be individualized,” Scott noted. Personalized treatment would encompass patients’ prior treatment, preferences, age, comorbidities, and other factors, including shared decision making with providers, he added.
The recommendations note different efficacies of the drugs, with a trivial-to-small benefit for the biologics certolizumab pegol and vedolizumab, and a moderate benefit for mirikizumab.
Advanced Treatment Risks
Advanced therapies are associated with a risk of serious infection and malignancies, along with lesser side effects such as fever, fatigue, and headache.
Brandon Ash, who was diagnosed with Crohn’s disease as a teen, is concerned the drugs might harm some people more than the disease does. He became addicted to opioids during his journey and never achieved long-term remission despite trying virtually every treatment option. His advanced therapy gave him six to eight good days with side effects of extreme fatigue and nausea.
“My life revolved around those treatments. It was not like the drug commercials. I didn’t dance. I didn’t wear bright colors, and I wasn’t grinning ear-to-ear,” Ash told The Epoch Times. “I basically struggled to live, hopping from one treatment to the next.”
His doctors described his surgery as a miracle, but the disease returned—until he made comprehensive lifestyle changes. He has since written a book about his experience: “Up From the Ashes.”
Ash stopped drinking alcohol, prioritized exercise, and began to think of food as medicine. He gave up sugar and used cannabidiol (CBD), the non-psychoactive form of marijuana, to address inflammation and pain rather than opioids that had been part of his treatment.
Of note, CBD has anti-inflammatory properties, though a small randomized trial with CBD found that a low dose had no effect on Crohn’s disease.
If he could do it over, Ash said he would demand more of his doctors and himself.
“You can’t take the shortcuts to life—orange prescription bottles and constant appointments with experts—and all of that,” he said. “At some point, there must be personal responsibility in our lives.”
Dietary Considerations
Scott noted growing evidence in favor of diet—particularly for mild cases—and patient interest in learning more about how to manage their disease through diet. However, the AGA guidelines strictly cover pharmacological treatment.
“I think it’s an exciting emerging field,” Scott said of diet. “But in the setting of moderate to severe disease, it’s not as well studied.”
Ash said doctors told him not to worry about what he ate, and he’s concerned that the new recommendations will undermine the importance of diet. “Diet has had a big effect. We eat garbage diets in the Western world, and we pay the consequences of it with inflammatory diseases,” he said.
The American College of Gastroenterology (ACG) guidelines—also updated this year and described by Scott as more holistic—recommend a Mediterranean or specific carbohydrate diet, but only for low-risk patients with mild disease under close monitoring.
The ACG guidelines also emphasize an aggressive advanced-therapy approach for patients with moderate-to-severe Crohn’s disease, much as the American Gastroenterological Association’s recommendations do. For the right patients, the new recommendations could be meaningful.
However, there’s caution in many unknowns when it comes to all forms of treatment for Crohn’s disease, the ACG guidelines commentary stated.
“Many recommendations remain conditional and based on low-quality evidence,” the authors of the ACG guidelines wrote in September. “Evidence for dietary therapies also remain limited, and while they may benefit select motivated patients with low-risk disease, reliance on diet alone should not delay timely escalation in more severe phenotypes.”
