Tumor necrosis factor-α antibodies (infliximab, adalimumab and certolizumab) in Crohn's disease: systematic review and meta-analysis

Abstract

Introduction: This meta-analysis compares the effectiveness and safety of tumor necrosis factor α (TNF-α) antibodies (infliximab, adalimumab and certolizumab) with either a placebo or each of them in the treatment of Crohn's disease (CD).

Material and methods: A systematic review of literature published up to November 2012 was performed and a meta-analysis of identified studies was carried out. We searched the following databases: PubMed, EMBASE, The Cochrane Library and others. Only randomized or clinical controlled trials were included.

Results: Nineteen clinical trials fulfilled the established criteria (5 studies for infliximab vs. placebo, 6 for each adalimumab or certolizumab vs. placebo and 2 comparing infliximab with adalimumab). The results of meta-analysis showed that anti-TNF therapy in patients with CD is safe and statistically significantly more effective when compared with the placebo for induction of remission at week 4 (RB = 1.90, 95% CI: 1.55-2.33, p < 0.00001), maintenance of remission at weeks 20-30 (RB = 1.86, 95% CI: 1.61-2.15, p < 0.00001) and at weeks 48-56 (RB = 2.75, 95% CI: 2.13-3.54, p < 0.00001) in patients who responded to the induction therapy and patients randomized before the induction. Anti-TNF agents were also superior to the placebo in fistula healing (during short-term induction, as well as long-term maintenance) and inducing CR-70 but not CR-100 at week 4. Moreover, the anti-TNF therapy had a significant effect on achieving both CR-70 and CR-100 during long-term maintenance.

Conclusions: Infliximab, adalimumab and certolizumab are effective as both induction and maintenance therapy in moderate to severe Crohn's disease in adults, including patients with fistulas. The safety profile was acceptable.

Keywords: Crohn's disease; meta-analysis; systematic review; tumor necrosis factor-α antibodies.

Figure 1

PRISMA flow diagram for selection of studies identified in the systematic review

Figure 2

The effect of anti-TNF agents compared with placebo on induction of remission at week 4

Figure 3

The effect of anti-TNF agents compared with placebo on maintenance of remission at week 48–56 (excluding study [24])

Figure 4

The effect of anti-TNF agents compared with placebo on complete fistula closure

Figure 5

The effect of anti-TNF agents compared with placebo on clinical response at week 4; 100 – CR

Figure 6

The effect of anti-TNF agents compared with placebo on clinical response during maintenance; 100 – CR (including study [24])

Figure 7

The effect of anti-TNF agents compared with placebo on risk of serious adverse events during induction

Figure 8

The effect of anti-TNF agents compared with placebo on risk of serious adverse events durning maintenance