Real-World Effectiveness of Advanced Therapies in Microscopic Colitis

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.