Biologic + behavioural therapy shows favourable signals in CATHARSIS trial

A novel therapeutic approach combining behavioural and biologic treatments appears feasible for the management of individuals with Crohn’s disease, based on feasibility and early outcomes from the CATHARSIS* trial.

To evaluate the potential of combining resilience intervention with biologics, the researchers enrolled adults with moderate-to-severe Crohn’s disease who were initiating anti-tumour necrosis factor or anti-interleukin-23 medications. Of the 109 eligible participants, 41 (mean age 40.3 years, 51 percent women) were randomized to either the active intervention (n=22) or attention control (n=19). [CCC 2026, abstract izag006.016]

The active intervention comprised a biologic plus a structured gut-brain behavioural therapy, whereas the participants in the comparator arm received a biologic plus general support. Both programmes were limited to seven sessions (12 weeks) and were delivered by therapists. Participants were blinded to their allocation.

The study outcomes included global well-being, clinical remission, and different measures of psychological and physical health. An expectancy questionnaire was completed following the first session.

Overall, the mean disease duration was 8.9 years. Based on the Patient-Reported Outcomes 2, a majority (39 percent) of participants had moderate disease, about a third (29 percent) had severe disease, 22 percent had mild disease, and 10 percent were in remission. Forty-four percent of participants reported steroid or opioid use, and half were bio-naïve. The most commonly used new biologic therapy was risankizumab (37 percent), followed by infliximab (17 percent).

Of note, more than half (54 percent) of the participants had ‘low resilience’ in the Resilience Scale for Inflammatory Bowel Disease (RISE-IBD). The RISE-IBD is a psychometric instrument designed to evaluate resilience across multiple domains in patients with IBD to better understand their coping mechanisms and to inform the development of individualized interventions. [BMC Gastroenterol 2025:21;25:390]

Participants in both groups held positive expectations that the behavioural programmes would improve Crohn’s disease symptoms and/or their quality of life. The mean expectancy ratings (out of 9) were 7.4 for how logical the intervention seemed, 6.1 for the likelihood of treatment success, and 6.6 for confidence in recommending the programme to others.

On average, participants predicted a 60-percent improvement at week 12, regardless of the treatment approach. According to the investigators, programme satisfaction was high and similar between treatment groups. To date, 31 patients have completed the treatment, with no dropouts.

“The full retention reflects strong engagement and acceptance of behavioural therapy in Crohn’s disease care. Continuation of the trial is therefore warranted,” said the researchers.

Gut-brain axis

There is an association between chronic intestinal inflammation and peripheral changes that disrupt homeostasis in the central nervous system. [Am J Transl Res 2024;16:6029-6040] A systematic review reported that the bidirectional effects of the gut-brain axis may influence both the natural history of IBD and its psychological manifestations. [Gut 2022;71:1773-1780]

“Novel treatment approaches are needed to raise the therapeutic ceiling in Crohn’s disease. Increasing evidence suggests that behavioural interventions targeting the gut-brain axis and psychological resilience may optimize clinical outcomes,” said the investigators.

In one study, a regimen comprising cognitive behavioural and mindfulness-based stress reduction induced stress resilience in patients with Crohn’s disease, thereby improving their well-being and modulating disease-associated inflammatory processes. [Brain Behav Immun Health 2021:19:100407]

“These early data support the rigor and quality of the CATHARSIS trial. Recruitment has been feasible and well accepted … Both programmes have yielded high expectations and satisfaction ratings, indicating successful masking of the hypothesis,” the investigators said.