BARCELONA, Spain — Patients with Crohn’s disease who continued to take an immunomodulator alongside anti-TNF treatment were substantially more likely to remain on anti-TNF therapy over 5 years than those receiving anti-TNF monotherapy, according to further analyses of the PROFILE trial.

These results were “really striking,” said study author Nurulamin Noor, MD, of the University of Cambridge, Cambridge, UK, who presented the latest findings at United European Gastroenterology (UEG) Week 2026 where he received a UEG Shining Star Award for his work.

In addition, “we found that withdrawing an immunomodulator [was associated with] much faster loss of response to the anti-TNF drug,” he noted.

“I think this study suggests we should be continuing long-term combination treatment,” he told meeting attendees.

Treatment Durability Takes Center Stage

PROFILE’s previously reported 5-year findings, presented at ECCO 2026 and subsequently published in The Lancet, showed that a top-down approach, in which combination therapy is initiated at diagnosis, was associated with better long-term outcomes, including fewer abdominal surgeries, hospitalizations, and stricturing or penetrating complications.

The current analyses focused on a different clinical question: how long patients remain on anti-TNF therapy, and whether continuing an immunomodulator is associated with greater treatment durability.

This is something seen increasingly in clinical practice — “people withdraw the immunomodulator,” said Noor.

PROFILE initially randomized 386 adults with newly diagnosed (median of just 2 weeks after diagnosis) active Crohn’s disease to immediate top-down treatment with infliximab plus an immunomodulator or an accelerated step-up strategy, in which treatment was escalated if patients did not respond adequately to initial therapy. Assigned treatment strategies continued for 48 weeks, after which patients received usual local care. Long-term medical records were available for 358 participants (93%), with a median follow-up of approximately 5 years.

Of 323 patients who received anti-TNF treatment during the follow-up, the median treatment persistence was 73 months. Treatment durability here refers to how long patients remained on anti-TNF treatment, rather than the duration of remission or clinical response, the study authors noted.

“We demonstrated much higher durability with anti-TNF therapy than any study previously published,” Noor told Medscape Medical News.

The investigators then examined treatment persistence according to whether patients received anti-TNF therapy alone or in combination with an immunomodulator, and how long combination treatment was maintained. The immunomodulator was selected by treating clinicians and was typically a thiopurine, most commonly azathioprine.

Over 70% of patients receiving sustained combination treatment remained on anti-TNF therapy at 5 years, compared with 35% of those receiving monotherapy.

Withdrawing the immunomodulator was associated with a shorter treatment persistence, a finding that could challenge the practice of discontinuing combination treatment after an initial period of disease control.

Patients receiving combination therapy for less than 6 months had the lowest anti-TNF treatment persistence; those treated for 6 months to 2 years had intermediate outcomes; and those continuing combination therapy for more than 2 years had the greatest persistence.

A Finding Beyond Antidrug Antibodies

One of the more unexpected findings was that combination therapy was associated with reductions in both immunogenic and nonimmunogenic treatment failure, suggesting that its benefits may extend beyond preventing antibody formation against anti-TNF drugs.

Although reduced immunogenicity with combination therapy has been demonstrated previously, the PROFILE analyses also found less loss of response among patients without detectable antidrug antibodies. This was “even more surprising,” Noor remarked, describing the finding as “novel.”

The distinction is clinically important because loss of response to anti-TNF therapy remains a major challenge in Crohn’s disease. Previous research suggests that approximately two thirds of patients experience treatment failure within 3 years.

In analyses examining potential clinical predictors, including smoking, BMI, and inflammatory burden, continued combination therapy emerged as the most consistent predictor of anti-TNF durability. Noor said it was the only clinical predictor identified for loss of response in the current analyses.

Overall, the findings from PROFILE suggest that early effective treatment may alter the long-term course of Crohn’s disease, while sustained combination therapy may help maintain treatment effectiveness.

Potential Risks of Prolonged Immunosuppression

Commenting on the findings, co-moderator, Alessandro Armuzzi, MD, professor of gastroenterology at Humanitas University and head of the Inflammatory Bowel Disease Unit at Humanitas Research Hospital, Milan, Italy, highlighted their practical implications. “The message is that if you start with infliximab, you should start in combination and keep on combination in the long term,” Armuzzi told Medscape Medical News.

He cautioned, however, against overlooking the possible consequences of prolonged immunosuppression. “Apparently, safety data in the first 5 years were not different, but we should keep in mind that long-term combination therapy could generate some safety risk,” he said.

An important distinction is that, although PROFILE was originally a randomized trial, the long-term comparison of combination therapy and monotherapy was observational, with treatment decisions made by clinicians.

The findings raise questions about the optimal timing of immunomodulator withdrawal and highlight the need for prospective studies to determine how best to balance treatment durability against the potential risks of prolonged combination therapy.

Noor reported receiving educational and travel grants, speaker fees, and/or advisory board fees from multiple pharmaceutical companies, including AbbVie, Bristol Myers Squibb, Celltrion, Johnson & Johnson, Lilly, Pfizer, and Takeda. Armuzzi reported no financial conflicts of interest relevant to the study.