For patients with moderate-to-severe Crohn’s disease (CD), infliximab and adalimumab appear to be most effective as first-line agents, according to a new systematic review of biologic therapies published in the journal Alimentary Pharmacology and Therapeutics.

For this study, researchers identified randomized controlled trials that included adults with moderate-to-severe CD treated with various biologic agents (i.e., infliximab, adalimumab, certolizumab pegol, vedolizumab, ustekinumab) as first- or second-line therapies compared with placebo or an active comparator. Efficacy and safety outcomes included induction and maintenance of clinical remission, and serious adverse events/infections, respectively. The treatments were ranked using surface under the cumulative ranking (SUCRA) probabilities, with higher scores representing higher ranking for efficacy and safety outcomes.

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Results showed that for induction of clinical remission, infliximab (SUCRA 0.93) and adalimumab (SUCRA 0.75) ranked highest in biologic-naive patients, however ustekinumab and vedolizumab were also found to be effective in these patients. For those with prior anti-tumor necrosis factor-α (TNF) exposure, particularly patients with primary nonresponse, evidence supports the use ustekinumab (moderate quality; SUCRA 0.71). In patients who have had secondary loss of response or intolerance to anti-TNF treatment, adalimumab may be more beneficial (low quality; SUCRA 0.91). 

Adalimumab and infliximab were also ranked highest for maintenance of remission in CD patients who had a response to induction therapy (SUCRA 0.97 and 0.68, respectively). In maintenance trials, ustekinumab was found to have the lowest risk of serious adverse events (SUCRA 0.72), while infection risk was lowest for both infliximab (SUCRA 0.83) and ustekinumab (SUCRA 0.71).

Based on the findings, the authors concluded that in patients with moderate-to-severe CD, infliximab or adalimumab may be “preferred” as a first-line treatment, while ustekinumab appears safe and effective as a second-line agent. However, as the results of this review were based on indirect comparisons, the authors concluded that “pragmatic head-to-head trials in both biologic-naıve and biologic-exposed patients are warranted to optimally inform relative positioning of newly available agents in clinical practice.”

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