Clinician Article
Comparative effectiveness of immunosuppressants and biologics for inducing and maintaining remission in Crohn's disease: a network meta-analysis.
PMID: 25448924
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Internal MedicineRelevance - 6/7
Newsworthiness - 6/7 -
GastroenterologyRelevance - 6/7
Newsworthiness - 5/7 -
Family Medicine (FM)/General Practice (GP)Relevance - 5/7
Newsworthiness - 5/7 -
General Internal Medicine-Primary Care(US)Relevance - 5/7
Newsworthiness - 5/7
Abstract
BACKGROUND & AIMS: There is controversy regarding the best treatment for patients with Crohn's disease because of the lack of direct comparative trials. We compared therapies for induction and maintenance of remission in patients with Crohn's disease, based on direct and indirect evidence.
METHODS: We performed systematic reviews of MEDLINE, EMBASE, and Cochrane Central databases, through June 2014. We identified randomized controlled trials (N = 39) comparing methotrexate, azathioprine/6-mercaptopurine, infliximab, adalimumab, certolizumab, vedolizumab, or combined therapies with placebo or an active agent for induction and maintenance of remission in adult patients with Crohn's disease. Pairwise treatment effects were estimated through a Bayesian random-effects network meta-analysis and reported as odds ratios (OR) with a 95% credible interval (CrI).
RESULTS: Infliximab, the combination of infliximab and azathioprine (infliximab + azathioprine), adalimumab, and vedolizumab were superior to placebo for induction of remission. In pair-wise comparisons of anti-tumor necrosis factor agents, infliximab + azathioprine (OR, 3.1; 95% CrI, 1.4-7.7) and adalimumab (OR, 2.1; 95% CrI, 1.0-4.6) were superior to certolizumab for induction of remission. All treatments were superior to placebo for maintaining remission, except for the combination of infliximab and methotrexate. Adalimumab, infliximab, and infliximab + azathioprine were superior to azathioprine/6-mercaptopurine: adalimumab (OR, 2.9; 95% CrI, 1.6-5.1), infliximab (OR, 1.6; 95% CrI, 1.0-2.5), infliximab + azathioprine (OR, 3.0; 95% CrI, 1.7-5.5) for maintenance of remission. Adalimumab and infliximab + azathioprine were superior to certolizumab: adalimumab (OR, 2.5; 95% CrI, 1.4-4.6) and infliximab + azathioprine (OR, 2.6; 95% CrI, 1.3-6.0). Adalimumab was superior to vedolizumab (OR, 2.4; 95% CrI, 1.2-4.6).
CONCLUSIONS: Based on a network meta-analysis, adalimumab and infliximab + azathioprine are the most effective therapies for induction and maintenance of remission of Crohn's disease.
Clinical Comments
Gastroenterology
The best way to compare the relative efficacy of two interventions is to undertake a head-to-head comparison. Even in such trials, there may be questions about how applicable the findings are to other patient populations, although the results are often generalized by clinicians because there are no other data. Indirect comparisons are even more sensitive to heterogeneity and have to be taken skeptically. For example, the trials employed in this exercise lasted from 4-106 weeks and came from different centers throughout the world. Another potential interesting factor might have been to tabulate the response rates in the control groups, but that information was not provided. Given the baseline differences that always exist between individual patients, these estimates may not be applicable to all of them. Thus, while the information is useful in a general sense, it actually may not affect clinical practice where treatment consists of trial and error until something works.
Gastroenterology
Network meta-analysis is a valid methodology, but makes assumptions about comparability of underlying studies and study populations that are difficult to fulfill. The devil here is in the details, and to draw conclusions from such indirect comparisons is extremely risky.
General Internal Medicine-Primary Care(US)
Crohn's immunosuppresive therapy is primarily managed by gastroeneterologists and not primary care physicians.
General Internal Medicine-Primary Care(US)
As a hospitalist, I have little occasion to prescribe the medications, but it is interesting to see the comparison of these meds.
General Internal Medicine-Primary Care(US)
This is yet again another key article that pushes us more toward earlier usage of anti-TNF therapy and/or combination therapy with thiopurine. This meta-analysis is further evidence that the newer approach to treating Crohn's disease with top-down methodology of anti-TNF +/- thiopurine is superior to starting with just a 5-asa or thiopurine first.
Internal Medicine
Good analysis but most pertinent for GI docs.
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