Real-world Effectiveness of Advanced Therapies in Microscopic Colitis

Clin Gastroenterol Hepatol. 2025 Dec 26:S1542-3565(25)01066-3. doi: 10.1016/j.cgh.2025.12.019. Online ahead of print.

Abstract

Background & aims: Microscopic colitis (MC) is a leading cause of chronic diarrhea, particularly in older adults. Although many patients respond to budesonide, refractory and dependent cases pose major therapeutic challenges. Although the off-label use of advanced inflammatory bowel disease therapies is expanding, robust real-world data remain scarce.

Methods: Through the ECCO CONFER network, we conducted a multinational, retrospective study in patients with MC treated with biologics or small molecules following budesonide failure or intolerance. We systematically analyzed clinical outcomes, treatment durability, and predictors of therapeutic success.

Results: Among 229 treatment cycles in 142 patients, anti-tumor necrosis factor (TNF) agents were most frequently initiated (55.9%), followed by vedolizumab (28.8%) and Janus kinase (JAK) inhibitors (9.2%). Short-term clinical response and remission rates were highest with JAK inhibitors (95.2% and 81.0%, respectively), significantly outperforming anti-TNFs, vedolizumab, and ustekinumab (P < .01). Long-term drug persistence mirrored these findings: JAK inhibitors demonstrated a markedly lower discontinuation rate (23.8%) compared with other agents (56.3%; odds ratio, 5.07; 95% confidence interval, 1.52-16.9; P = .008). Multivariate analysis confirmed drug class as the only independent predictor of therapy continuation. Despite advanced therapies, 4.2% of patients ultimately required surgical intervention.

Conclusions: This real-world study demonstrates the promising short- and long-term effectiveness of advanced therapies-particularly JAK inhibitors-in budesonide-refractory and budesonide-dependent MC. These findings pave the way for dedicated prospective trials and highlight evolving therapeutic strategies in MC.

Keywords: Advanced Therapy; Biologics; Collagenous Colitis; JAK Inhibitor; Lymphocytic Colitis; Microscopic Colitis; Small Molecules.