Infliximab and adalimumab are shown to be effective for induction and maintenance of clinical remission in patients with moderate to severe Crohn disease, according to a study in Lancet Gastroenterology and Hepatology.

Researchers conducted an updated systematic review and network meta-analysis to compare the efficacy and safety of tumor necrosis factor (TNF) antagonists (infliximab, adalimumab, and certolizumab pegol), anti-integrins (vedolizumab), anti-IL-12/23p40 agents (ustekinumab), and anti-IL-23p19 agents (risankizumab) alone or combined with immunosuppressants as treatment for moderate to severe Crohn disease in biologic-naive patients and in those with prior biologic exposure.

The study authors searched Medline, EMBASE, the Cochrane CENTRAL Register of Controlled Trials, conference proceedings, trial registries, and unpublished data from inception to June 3, 2021, for relevant phase 2 or phase 3 randomized controlled trials. The primary efficacy outcome was induction of clinical remission, defined by a Crohn Disease Activity Index (CDAI) score <150, and maintenance of remission in patients with response to induction therapy.


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Overall, 31 trials with 8020 participants were included. In the network meta-analysis of 15 randomized controlled trials with 2931 biologic-naive patients, moderate confidence was found in estimates supporting infliximab monotherapy (odds ratio [OR], 4.53; 95% CI, 1.49-13.79), infliximab with azathioprine (OR, 7.49; 95% CI, 2.04-27.49), adalimumab (OR, 3.01; 95% CI, 1.25-7.27), or ustekinumab (OR, 2.63; 95% CI, 1.10-6.28) vs certolizumab pegol for induction of remission. Low confidence was found for estimates supporting infliximab combination therapy vs vedolizumab (OR, 3.76; 95% CI, 1.01-14.03) and certolizumab pegol (OR, 7.49; 95% CI, 2.04-27.49).

In 10 randomized controlled trials with 2479 patients who had previous biologic exposure, moderate confidence was observed for estimates supporting risankizumab (OR, 2.10; 95% CI, 1.12-3.92) vs vedolizumab for inducing remission. Low confidence was found for estimates supporting adalimumab (OR, 2.82; 95% CI, 1.20-6.62) vs vedolizumab for patients who had biologic exposure.

Based on the network meta-analysis, no agent was clearly superior compared with other agents for clinical response induction in patients with biologic exposure, with the overall highest ranking for risankizumab (surface under the cumulative ranking curve [SUCRA], 0.87) and ustekinumab (SUCRA, 0.67).

The direct meta-analysis demonstrated that all agents were superior to placebo for maintenance of remission, with the highest ranking for infliximab with azathioprine (SUCRA, 0.87) and adalimumab (SUCRA, 0.78), followed by infliximab monotherapy (SUCRA, 0.63).

The researchers noted between-study heterogeneity among patients and trial design features. Additionally, differences in unmeasured confounders across the studies could affect the relative treatment effect.

“This updated systematic review and network meta-analysis highlights the role of infliximab and adalimumab (either in combination with azathioprine or as monotherapy) as first-line agents for inducing and maintaining clinical remission, and identifies IL-23 blockade with ustekinumab or risankizumab as a potentially effective strategy in patients with previous TNF antagonist exposure,” the investigators concluded.

Disclosure: Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

Reference

Singh S, Murad MH, Fumery M, et al. Comparative efficacy and safety of biologic therapies for moderate-to-severe Crohn’s disease: a systematic review and network meta-analysis. Lancet Gastroenterol Hepatol. 2021;6(12):1002-1014. doi: 10.1016/S2468-1253(21)00312-5