Combination therapy in IBD

Combination therapy in IBD

December 15, 2020

Issue 24

Clinical Question

Does choice of agent or concomitant use of an immunomodulator affect efficacy of anti-TNF therapy for IBD?

Editor’s Bottom Line

Combination therapy was associated with better outcomes for both adalimumab and infliximab. Although confounding factors cannot be excluded, these data support combination therapy as a default strategy for all anti-TNF agents.


Targownik LE, Benchimol EI, Bernstein CN, et al. Combined Biologic and Immunomodulatory Therapy is Superior to Monotherapy for Decreasing the Risk of Inflammatory Bowel Disease-Related Complications. J Crohn’s Colit. 2020;14(10):1354–63;


In this study, researchers retrospectively examined health administrative data from four Canadian provinces, including 78,413 patients with IBD. Fourteen percent of patients were dispensed at least one dose of an anti-tumour necrosis factor (anti-TNF) therapy, most commonly infliximab. Roughly 39% of anti-TNF recipients also received concomitant therapy with immunomodulators, most commonly azathioprine or 6-MP. Between 8 and 32 years of data were available from each province.

Multivariate analysis found that, compared to anti-TNF monotherapy, combination therapy was associated with a lower likelihood of treatment ineffectiveness, defined as unplanned IBD-related hospitalization, surgery, corticosteroid use or a switch to another anti-TNF agent (Adjusted Hazard Ratio [aHR] for Crohn’s disease (CD): 0.77; 95% Confidence Interval [CI], 0.66–0.90 and aHR for ulcerative colitis (UC): 0.72; 95% CI, 0.62–0.84). Treatment outcomes did not differ according to choice of anti-TNF agent.

Thiopurine-based combination therapy significantly decreased the risk of treatment ineffectiveness in both CD (aHR: 0.76; 95% CI, 0.67–0.86) and UC patients (aHR: 0.70; 95% CI, 0.59–1.24). Use of methotrexate was associated with a higher likelihood of treatment ineffectiveness than azathioprine in UC patients (aHR: 1.53; 95% CI, 1.01–2.28), but not in CD (aHR: 1.22; 95% CI 0.96–1.54).


Study Design: Retrospective database analysis

Funding: The Crohn’s and Colitis Canada Grants in Aid of Research and the Helmsley Foundation

Allocation: Not applicable

Setting: Multicenter

Level of Evidence: 2b