Original article—alimentary tract
Efficacy and Safety of Tumor Necrosis Factor Antagonists in Crohn's Disease: Meta-Analysis of Placebo-Controlled Trials

https://doi.org/10.1016/j.cgh.2008.03.014Get rights and content

Background & Aims: We performed a meta-analysis of placebo-controlled trials to evaluate safety and efficacy of tumor necrosis factor (TNF) antagonists for Crohn’s disease. Methods: We searched MEDLINE, Cochrane Library, and EMBASE. The primary end points were clinical remission for luminal Crohn's disease and fistula closure at ≥2 consecutive visits. Deaths, serious infections, and malignancies were also analyzed by the methods of Peto and Der Simonian and Laird. Results: Fourteen luminal Crohn's disease trials enrolled 3995 patients. In overall analysis, anti-TNF therapy was effective for induction of remission at week 4 (mean difference, 11%; 95% confidence interval [CI], 6%–16%; P < .001) and maintenance of remission at weeks 20–30 in patients who responded to induction therapy and in patients randomized before induction (mean difference, 23%; 95% CI, 18%–28% and mean difference, 8%; 95% CI, 3%–12%, respectively; P < .001 for all comparisons). Ten studies evaluated anti-TNF for treatment of fistulizing Crohn's disease, involving 776 patients. In overall analysis, anti-TNF therapy was effective for fistula closure only in maintenance trials after open-label induction (mean difference, 16%; 95% CI, 8%–25%; P < .001). In 21 studies enrolling 5356 individuals, anti-TNF therapy did not increase the risk of death, malignancy, or serious infection. Conclusions: Infliximab, adalimumab, and certolizumab are effective in luminal Crohn's disease. Efficacy of anti-TNF agents other than infliximab in treating fistulizing Crohn's disease requires additional investigations. A longer duration of follow-up and a larger number of patients are required to better assess the safety profile of TNF antagonists in Crohn's disease.

Section snippets

Materials and Methods

See supplemental material “Web Materials and Methods” online at www.cghjournal.org.

Luminal Crohn's Disease

Fourteen studies involving 3955 patients were included (Table 1, Table 2). There were 2417 patients treated with anti-TNF agents (infliximab 308, adalimumab 713, certolizumab 830, CDP571 374, etanercept 23, onercept 169) and 1538 patients treated with placebo.

Safety Results

Twenty-one studies involving 5356 patients were included (Table 4 and web Tables 2–4; see supplemental material online at www.cghjournal.org). There were 3341 patients in the anti-TNF groups and 2015 patients in the control groups. The median follow-up was 24 weeks for the 21 trials included in safety analysis (range, 4–60 weeks).

Discussion

This is the first meta-analysis of anti-TNF therapy in luminal and fistulizing CD that includes all 6 agents evaluated in RCTs.

In luminal CD, anti-TNF therapy was more effective than placebo for induction of clinical remission at week 4, with a number needed to treat (NNT) of 9. By reanalyzing data from 14 trials, we were able to include 615 adult CD patients treated with certolizumab and 288 with adalimumab. Both drugs were effective with a NNT of 7 and 10 for adalimumab and certolizumab,

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  • Cited by (0)

    Drs Deltenre and de Suray contributed equally to this work.

    Dr Sandborn has received research support from Centocor, Abbott Laboratories, UCB Pharma (formerly Celltech), Immunex (now Amgen), and Serono International; is a consultant to Centocor, Abbott Laboratories, UCB Pharma (formerly Celltech), Immunex (now Amgen), and Serono International; and has participated in continuing medical education events indirectly sponsored by Centocor, Schering-Plough, Abbott Laboratories, and UCB Pharma (formerly Celltech). Dr Colombel is a consultant to Centocor, Abbott Laboratories, and UCB Pharma (formerly Celltech) and has participated in continuing medical education events indirectly sponsored by Centocor, Schering-Plough, Abbott Laboratories, and UCB Pharma (formerly Celltech).

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