SAN FRANCISCO—Treatment of Crohn’s disease be challenging for clinicians, partly due to an array of options that include medical therapy, surgery and dietary interventions, as well as varying patient preferences for these options. At the 2025 Crohn’s & Colitis Congress, three researchers discussed the merits of each approach as a first-line therapy.

Medical Therapy

“When we look at our clinical trials and we wonder why patients reach a therapeutic ceiling, it’s because the average disease duration is six, seven or eight-plus years. After 12 years of irreversible bowel damage, are we actually going to be able to get the outcomes that we need for our patient?” asked Marla Dubinsky, MD, a pediatric gastroenterologist at Mount Sinai Hospital, in New York City.

“The argument here is really around the fact that the earlier and most impactful window of opportunity is as close to diagnosis as possible, whereby a biologic, anti-integrin or anti-cytokine approach that we choose, we’re actually able to do something while the disease is in more of an inflammatory state, [before there is] irreversible damage,” Dr. Dubinsky said.

She cited several studies with better outcomes when patients received early medical intervention, including a study of combined immunotherapy (infliximab plus azathioprine), as well as the EXTEND (adalimumab), REACT (early combined immunosuppression), CALM (adalimumab) and PROFILE (infliximab plus immunomodulator) studies.

“Early intervention is what matters, and maybe negates all predictive prognostic markers,” Dr. Dubinsky said, adding patients often fail to reach therapeutic targets because they start the drug too late. “We now have various [lines of] evidence, starting back to 2008 [and continuing] up to 2024, that we should be starting early, effective therapy and not wasting our time stepping up with steroids and thiopurines.”

Surgical Intervention

Samuel Eisenstein, MD, an associate professor of surgery at UC San Diego Health, discussed treatment of patients with limited ileal CD who are naive to biologics and highlighted the potential of ileocecal resection. Specifically, he referred to patients with inflammatory disease, not those with fibrostenotic/obstructive disease, or penetrating or fistulizing disease or abscesses. “[Resection] could be considered as first line in a select subset of patients,” he said.

Dr. Eisenstein pointed out that around 80% of CD patients eventually undergo surgery, and many of them are inflammatory patients. He also said recurrence rates for CD are nearly identical after surgery or biologic therapy. “As a surgeon, I think one of the most important things that I try to impart to patients is that surgery is going to be most successful when it’s done in a patient who’s at their healthiest,” he said. “The question I have for a lot of my colleagues here is, how sick can we let a patient get before they go to surgery?”

He cited a Swedish trial that compared surgery with infliximab in a drug-naive patient population. That study failed to recruit enough patients to get to completion, but investigators found no difference in the primary end point of the Crohn’s Disease Activity Index over time.

More recently, the LIR!C randomized controlled trial, conducted in the Netherlands and United Kingdom between 2008 and 2015, compared laparoscopic ileocecal resection with infliximab treatment and found no difference in the primary end point of the Inflammatory Bowel Disease Questionnaire, but scores on the Short Form-36 at six and nine months were better for the surgery group. At one year, 84% of the infliximab group and 79% of the surgery group were in endoscopic remission.

A meta-analysis of those two trials and six retrospective studies found reduced need for a second surgery compared with need for surgery after medical therapy (odds ratio, 0.32; P<0.0001) and a longer resection-free survival after surgery (hazard ratio [HR], 0.56; P=0.004). A sub-analysis of the terminal ileum found a lower probability of a second surgery at five years compared with follow-up surgery after medical therapy (HR, 0.18; P=0.03).

The LIR!C study authors analyzed cost-effectiveness of the two approaches, he noted, and found significantly lower costs in the surgery group.

Dr. Eisenstein also addressed patients’ attitudes about surgery, noting that a survey of 80 British patients in the 1990s found that 74% would have preferred to undergo surgery earlier; none said they would rather have waited longer.

He said his own approach is to offer up-front surgery to CD patients with isolated fibrostenotic disease and medical therapy optimization followed by surgery for those with penetrating disease.

Diet Modification

Oriana Damas, MD, an associate professor of medicine at the University of Miami Miller School of Medicine, discussed the potential for IBD-specific diets as a first-line therapy for mild to moderate CD. She noted that the Western diet—particularly its ultra-processed foods, total fats, meats and decreased consumption of fruits and vegetables—has been identified as a culprit for the development of IBD across multiple studies.

“I think that any provider that you speak to or our patients … will tell you that they do think that diet plays a role when it comes to IBD risk. Perhaps what’s not unanimous across the board is counseling [patients about] diet once the disease actually starts to occur. I have many patients that have been told by providers that diet doesn’t play a role once disease sets in,” Dr. Damas said.

She said advanced therapies are important for moderate to severe CD, but multiple studies have shown that net clinical remission after one year of treatment with biologic therapy is low, ranging from 6.7% to 34.8% across various biologics. “There is this therapeutic ceiling that remains stubbornly low for our patients, even though we have many different advanced therapies now available in the market,” Dr. Damas noted.

One argument for a dietary intervention is safety, although this approach can lead to very restrictive diets and must be done under the supervision of a provider and registered dietitian. Patients often are more accepting of dietary modification than surgery or medication. “I can bet you [almost all patients] talk about diet and they want to know [about it], and they’re much more likely to accept diet as a therapy than any other advanced therapy, especially if they [have a] mild phenotype,” she said.

There are good options with CD, including exclusive enteral nutrition, which was superior to corticosteroid use in a trial of 37 children, leading to mucosal healing in 74% of cases versus 33% with corticosteroids (P<0.05).

https://pubmed.ncbi.nlm.nih.gov/39167096/Other options include 50% enteral nutrition or gradual phasing out of enteral nutrition. Dr. Damas discussed the Crohn’s Disease Exclusion Diet, which starts out at 50% enteral nutrition and decreases to 25%, followed by a more long-term maintenance phase that is more liberal. She presented evidence that this tactic outperformed exclusive enteral nutrition in achieving sustained remission (87.5% vs. 56.0%) and led to a 77% reduction in fecal calprotectin.

Partial enteric nutrition (PEN) also can be combined with advanced therapies, she said, highlighting a review showing that it can reduce relapses when combined with anti–tumor necrosis factor therapy.

There are other dietary interventions in development, including “reverse engineering” a smoothie to mimic PEN, with ingredients such as bananas, avocado oil, strawberries, yogurt, egg whites, honey and almond butter. Researchers have “found promising results in terms of achieving clinical remission and some improvements in [C-reactive protein] as well as in fecal calprotectin, so it’s definitely a potential option that needs to be studied more,” Dr. Damas said.

For patients who don’t want enteral-based diets, another option is the Mediterranean diet, with one study showing that it had similar efficacy to the specific carbohydrate diet with respect to symptomatic remission, fecal calprotectin response and C-reactive protein response at six weeks, Dr. Damas said. “In my practice, I often leverage the Mediterranean diet as a maintenance therapy, especially if I’m able to get patients on partial enteral nutrition for induction purposes.”

—Jim Kling

Dr. Damas reported no relevant financial disclosures. Dr. Dubinsky reported financial relationships with AbbVie, Arena, AstraZeneca, BMS, Celgene, Gilead, Janssen, Lilly, Merck, Mi Test Health, Pfizer, Prometheus, Takeda, Target RWE and Trellus. Dr. Eisenstein reported a financial relationship with Takeda.