Global 
Deutschland Colon to Rectum
Am J Gastroenterol. 2026;121(2):410-423
Effectiveness and safety of advanced combination treatment in patients with refractory inflammatory bowel disease or concomitant immune-mediated disease or extraintestinal manifestations: A multicenter Canadian study
Introduction: Owing to the therapeutic ceiling associated with inflammatory bowel disease (IBD) therapies, some patients may require 2 advanced therapeutic agents, known as advanced combination treatment (ACT) to control disease or treat associated extraintestinal manifestations (EIMs).
Methods: The authors included adult patients with IBD from 9 Canadian centers treated with either 2 biological therapies, a biological plus an oral small molecule, or 2 small molecules. Indications for ACT were the following: (i) refractory IBD, (ii) uncontrolled immune mediated diseases, and (iii) uncontrolled EIMs. Primary outcomes were cumulative rates of clinical and endoscopic response and remission at 6 and 12 months. Secondary outcomes included serious adverse events and infections. Cox-proportional hazard analyses identified independent predictors of treatment effectiveness.
Results: 105 IBD patients (76 Crohn’s disease, 29 ulcerative colitis) with median age 35 years (interquartile range, 35.4–40.8) were included. At baseline, 39% had perianal involvement, 58% had failed at least 3 advanced therapies, and 40% had previous surgery. The primary reason for ACT was refractory IBD (63.8%), with the add-on approach used in 97.1% cases. The most frequent combination was antitumor necrosis factor + anti-integrin. At 12 months, cumulative rates of clinical and endoscopic response were 60.0% and 32.4%, respectively, and remission rates were 29.5% and 28.6%. Perianal disease was associated with reduced clinical remission (hazard ratio [HR] = 0.33, 95% confidence interval [CI]: 0.17–0.65; p = 0.001) and endoscopic response (HR = 0.42, 95% CI: 0.12–0.50; p = 0.001). Longer disease duration (HR = 0.96, 95% CI: 0.92–0.99; p = 0.035) and baseline steroid use (HR = 0.39; p = 0.006) was associated with reduced clinical remission. Serious adverse events and infections occurred in 12.4% and 7.6% of patients, respectively.
Discussion: ACT was effective in achieving clinical and endoscopic outcomes in patients with refractory IBD or concomitant immune-mediated diseases/EIMs, with favorable safety profile.