Upfront Combination Therapy, Compared With Monotherapy, for Patients Not Previously Treated With a Biologic Agent Associates With Reduced Risk of Inflammatory Bowel Disease-related Complications in a Population-based Cohort Study.

Background & Aims: Although guidelines recommend inclusion of immune modulators in anti-tumor necrosis factor (TNF) initiation therapy for Crohn's disease (CD) or ulcerative colitis (UC), there are limited data on the incremental effectiveness of this treatment strategy from the real world.

Methods: We collected data from the Manitoba Inflammatory Bowel Disease (IBD) Epidemiology database on persons with CD (n=852) or UC (n=303), from 2001 through 2016, who began treatment with a TNF antagonist. New and/or continuing users of immunomodulators at the time anti-TNF therapy began were considered recipients of combination therapy. The main outcome was treatment ineffectiveness (IBD-related hospitalization, intestinal resection, corticosteroid use, or change of anti-TNF agent) during TNF antagonist-based therapy or within 90 days after the anti-TNF agent was discontinued. We used Cox proportional hazards models to assess the association between concomitant use of immunomodulators and treatment ineffectiveness.

Results: In patients with CD, combination therapy was associated with a significant decrease in likelihood of treatment ineffectiveness (adjusted hazard ratio [aHR] for ineffectiveness, 0.62; 95% CI, 0.49-0.79). However, this association was not significant in patients with UC (aHR, 0.82; 95% CI, 0.56-1.20). In patients with CD, combination therapy was also associated with increased time to first IBD-related hospitalization (aHR 0.53; 95% CI, 0.36-0.80) and switching anti-TNF agents (aHR, 0.63; 95% CI, 0.41-0.97), but not associated with IBD-related surgery (aHR, 0.76; 95% CI, 0.51-1.12) or new or recurrent use of corticosteroids (aHR, 0.75; 95% CI, 0.55-1.04).

Conclusion: In an analysis of a database of real-world patients with IBD, we associated initiation therapy with a combination immune modulators and anti-TNF agents with a decreased likelihood of treatment ineffectiveness for patients with CD but not UC.