Professor El-Omar has selected Dr Javier Gisbert and Dr María Chaparro from the Gastroenterology Department, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid (UAM), and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain to do the next #GUTBlog. Dr Javier Gisbert is the first author and Dr María Chaparro is the senior author.

The #GUTBlog focusses on the paper “Withdrawal of antitumour necrosis factor in inflammatory bowel disease patients in remission: a randomised placebo-controlled clinical trial of GETECCU” which was published in paper copy in GUT in March 2025.

Dr Javier Gisbert and Dr María Chaparro write: 

“A groundbreaking study on anti-TNF withdrawal in IBD: the EXIT Trial

Inflammatory bowel disease (IBD), encompassing Crohn’s disease and ulcerative colitis, has been revolutionised by anti-TNF biologics. While these therapies effectively induce and maintain remission, their long-term use raises concerns regarding adverse events and healthcare costs. Until now, whether anti-TNF discontinuation is a feasible and safe strategy for selected patients has remained an open question.

A pioneering study led by Drs. Javier P. Gisbert and María Chaparro from Hospital Universitario de La Princesa and the Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD) sought to address this critical issue. Funded by the Instituto de Salud Carlos III and endorsed by the Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa (GETECCU), this randomised, placebo-controlled clinical trial—the EXIT trial—has provided novel insights into the feasibility of anti-TNF withdrawal in IBD patients in stable remission. The study’s findings, recently published in Gut, have received significant recognition, including the Investigator Initiated Study Award at the European Crohn’s and Colitis Organisation (ECCO) Congress.

Study design and objectives

The EXIT trial aimed to determine whether withdrawing anti-TNF therapy in patients with IBD in stable remission would lead to a significant increase in clinical relapse rates compared to those who continued therapy. Conducted across 33 Spanish hospitals, the study enrolled 140 patients with ulcerative colitis or Crohn’s disease. These patients had been in clinical remission for at least six months under standard-dose anti-TNF therapy (infliximab or adalimumab) and concomitant immunomodulators.

Participants were randomly assigned to either maintain their anti-TNF therapy or transition to placebo while continuing immunomodulator treatment. The primary endpoint was sustained clinical remission at 12 months, with secondary objectives including relapse-free time, endoscopic and radiological disease activity, quality of life, and treatment safety.

Key findings

Results from the EXIT trial demonstrated that 84% of patients in the maintenance arm and 76% in the withdrawal arm remained in clinical remission after one year. Importantly, the difference was not statistically significant, suggesting that discontinuation of anti-TNF therapy may be a viable option in carefully selected patients. Furthermore, there were no significant differences in the presence of severe endoscopic lesions between the groups at 12 months. However, a higher proportion of patients in the withdrawal arm exhibited elevated faecal calprotectin levels, a biomarker associated with inflammation and potential relapse risk.

The safety profile of both strategies was comparable, with serious adverse events occurring in 4% of patients who maintained anti-TNF therapy and in 7% of those who discontinued treatment. These findings reinforce the potential feasibility of anti-TNF withdrawal without exposing patients to a significant increase in adverse effects.

Implications for clinical practice

The EXIT trial provides compelling evidence that, in a subset of IBD patients with well-defined remission criteria, anti-TNF discontinuation can be considered as part of a personalised treatment approach. While the study supports the possibility of safely withdrawing anti-TNF therapy, it underscores the need for close monitoring, particularly in patients with elevated faecal calprotectin, which was the only predictive factor for relapse identified.

These results have the potential to shape future treatment paradigms, encouraging a shift towards tailored therapy strategies that balance long-term efficacy with safety and cost-effectiveness. Given the high financial burden of biologic therapy, identifying patients who can safely discontinue anti-TNF treatment without compromising disease control could have significant clinical and economic implications.

Conclusion

The EXIT trial represents a major step forward in the optimisation of IBD management. By demonstrating that anti-TNF withdrawal does not necessarily lead to higher relapse rates in appropriately selected patients, this study opens the door for more personalised treatment strategies. Future research should focus on refining predictive biomarkers and extending long-term follow-up to further elucidate the role of treatment de-escalation in IBD care.

These groundbreaking findings position the EXIT trial as a milestone in IBD research, paving the way for safer, cost-effective, and individualised therapeutic approaches in the years to come.”

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Dr Javier P Gisbert

Dr María Chaparro