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. Journal Articles uri icon

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abstract

  • 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: We 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: We included 105 IBD patients (76 Crohn's disease, 29 ulcerative colitis) with median age 35 years (Interquartile Range 35.4-40.8). 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.

authors

  • Solitano, Virginia
  • Ogunsakin, Ropo Ebenezer
  • Yuan, Yuhong
  • Bernstein, Charles N
  • Bessissow, Talat
  • Bressler, Brian
  • Hoentjen, Frank
  • van Lierop, Lisa
  • Leung, Yvette
  • Ma, Christopher
  • Marshall, John Kenneth
  • Narula, Neeraj
  • Alahmari, Mohammed
  • Mccurdy, Jeffrey D
  • Murthy, Sanjay
  • Panaccione, Remo
  • Rosenfeld, Greg
  • Milgrom, Raquel
  • Silverberg, Mark
  • Jairath, Vipul

publication date

  • June 5, 2025