Hazlewood GS, et al. Comparative effectiveness of immunosuppressants and biologics for inducing and maintaining remission in Crohn’s disease: a network meta-analysis. Gastroenterology. 2015 Feb;148(2):344-54.e5; quiz e14-5.

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Key Findings: 

“One good-quality RCT and one poor-quality RCT were included. Intravenous infliximab was compared to oral ciclosporin, azathioprine, and the combination of azathioprine and infliximab among moderate-to-severe ulcerative colitis patients without adequate response to corticosteroid treatment. In a pragmatic trial, there was no significant difference in quality-adjusted survival, mortality, colectomy rates, time to colectomy, lengths of hospital stay after randomization, severe adverse reactions or severe adverse effects, and quality of life measures. However, ciclosporin was associated with longer log-transformed hospital stays than infliximab. In the same trial, the UK resource use was considered. It was concluded that the total health service costs for ciclosporin were considerably lower than infliximab and ciclosporin was not less effective than infliximab.

In a good-quality RCT, the combination of intravenous infliximab and oral azathioprine was significantly more effective than infliximab or azathioprine alone in corticosteroid-free remission at week 16. However, infliximab alone was not significantly more effective than azathioprine alone for the same outcome. The combination was more effective than azathioprine alone in mucosal healing at week 16, but similarly effective as infliximab. Due to limited evidence identified, further research on the clinical effectiveness and cost-effectiveness of biologics compared to immunomodulators in patients without previous exposure to these two types of drugs may be needed.”

Targownik LE, et al. Combined Biologic and Immunomodulatory Therapy is Superior to Monotherapy for Decreasing the Risk of Inflammatory Bowel Disease-Related Complications. J Crohns Colitis. 2020 Jul 10:jjaa050. Epub ahead of print.

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Methods: We collected health administrative data from four Canadian provinces representing 78 413 patients with inflammatory bowel disease [IBD] of whom 11 244 were prescribed anti-tumour necrosis factor [anti-TNF] agents. The outcome of interest was the first occurrence of treatment failure: an unplanned IBD-related hospitalization, IBD-related resective surgery, new/recurrent corticosteroid use or anti-TNF switch. Multivariable Cox proportional hazards modelling was used to assess the association between the outcome of interest and receiving combination therapy vs anti-TNF monotherapy. Multivariable regression models were used to assess the impact of choice of immunomodulator or biologic on reaching the composite outcome, and random effects generic inverse variance meta-analysis of deterministically linked data was used to pool the results from the four provinces to obtain aggregate estimates of effect.

Results: In comparison with anti-TNF monotherapy, combination therapy was associated with a significant decrease in treatment ineffectiveness for both CD and UC (CD: adjusted hazard ratio [aHR] 0.77, 95% confidence interval [CI] 0.66-0.90; UC: aHR 0.72, 95% CI 0.62-0.84). Combination therapy was equally effective for adalimumab and infliximab in CD. In UC azathioprine was superior to methotrexate as the immunomodulatory agent (aHR = 1.52 [95% CI 1.02-2.28]) but not CD (aHR = 1.22 [95% CI 0.96-1.54]).