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
Virginia Solitano, Ropo Ebenezer Ogunsakin, Yuhong Yuan, Çharles N. Bernstein, Talat Bessissow, Brian Bressler, Frank Hoentjen, L van Lierop, Yvette Leung, Christopher Ma, John K. Marshall, Neeraj Narula, Mohammed Alahmari, Jeffrey D. McCurdy, Sanjay K. Murthy, Remo Panaccione, Greg Rosenfeld, Raquel Milgrom, Mark S. Silverberg, Vipul Jairath
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.