New data from the PROFILE trial show that Crohn's patients who kept taking an immunomodulator alongside anti-TNF therapy were far more likely to stay on treatment at 5 years — over 75% vs. just 40–45% on monotherapy. Dropping the immunomodulator was tied to faster loss of response. Researchers say the findings make a strong case for sticking with long-term combination therapy.
New analyses from the PROFILE trial, presented at UEG Week 2026, offer a compelling argument for keeping Crohn's disease patients on combination therapy — anti-TNF plus an immunomodulator — for the long haul. Patients who sustained combination treatment were dramatically more likely to still be on anti-TNF therapy at the 5-year mark, while those who had their immunomodulator withdrawn saw a much faster loss of response. The longer the combination was maintained, the better the outcomes.
Perhaps the most surprising finding: the benefit of combination therapy extended beyond just preventing antidrug antibodies. Even patients without detectable antibodies showed less treatment failure when on combo therapy — a novel finding that suggests the immunomodulator's role may be broader than previously understood. Continued combination therapy was also the only consistent clinical predictor of anti-TNF durability across all analyses.
By the Numbers:
75% of patients on sustained combination therapy remained on anti-TNF at 5 years
Why it matters: Loss of response to anti-TNF therapy is one of the biggest challenges in managing Crohn's disease. These findings push back against the common practice of withdrawing immunomodulators after initial disease control, suggesting that doing so may cost patients years of effective treatment — though experts caution that long-term immunosuppression risks still need prospective study.
