Efficacy and safety of antiintegrin antibody for inflammatory bowel disease: a systematic review and meta-analysis

Abstract

We sought to evaluate the safety and efficacy of available biologics that inhibit T-cell migration by blocking α4β7 integrins in inflammatory bowel diseases. The aim of this study is to evaluate whether Crohn disease (CD) patients receiving either vedolizumab or natalizumab have any different effect in CD Activity Index (CDAI). Using Medline, Excerpta Medica dataBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and Google Scholar until October 31, 2013, we identified 10 studies examining the safety and efficacy of specific integrin inhibitors—vedolizumab, which targets an epitope comprising the α4β7 heterodimer; natalizumab, which recognizes the α4 integrin subunit; etrolizumab, which is specific for the β7 subunit—in the treatment of CD and ulcerative colitis (UC). CD patients receiving either vedolizumab or natalizumab demonstrated a modest increase in remission rate, when compared with that of the placebo group. Further, although both treatments reduced the CDAI slightly, the observed clinical response was less robust than that of the remission rate. UC patients treated with vedolizumab and natalizumab were found to show more prominent increases in both remission and clinical response, compared with placebo, than patients with CD. Etrolizumab, however, was not found to significantly affect either response or remission rates in UC patients. Biologics targeting integrins show promise as therapeutics in the treatment of inflammatory bowel disease in patients who are either nonresponsive or intolerant to traditional approaches, though further research is necessary to optimize treatment efficacies.

FIGURE 1

Flowchart of study selection. RCT = randomized controlled trial.

FIGURE 2

Efficacy and safety of anti-α4β7 antibody in the treatment of CD. Forest plot comparing the effect of anti-α4β7 antibodies on (A) the clinical remission rate, (B) the clinical response rate, and (C) the SAEs rate versus placebo control. 1st AU = first author, CD = Crohn disease, CI = confidence interval, Lower limit = lower bound of the 95% CI, Upper limit = upper bound of the 95% CI, SAE = serious adverse events.

FIGURE 3

Efficacy and safety of anti-α4β7 antibody in the treatment of UC. Forest plot comparing the effect of anti-α4β7 antibodies on (A) the clinical remission rate, (B) the clinical response rate, and (C) the SAEs rate versus placebo control. 1st AU = first author, CI = confidence interval, Lower limit = lower bound of the 95% CI, SAE = serious adverse events, UC = ulcerative colitis, Upper limit = upper bound of the 95% CI.

FIGURE 4

Evaluation of meta-analysis sensitivity by the ‘leave-one-out’ approach. Clinical remission rate in (A) pooled CD studies, and (B) pooled UC studies, neglecting the specified trials. CD = Crohn disease, CI = confidence interval, Lower limit = lower bound of the 95% CI, UC = ulcerative colitis, Upper limit = upper bound of the 95% CI.

FIGURE 5

Funnel plots for clinical remission rate in (A) CD and (B) UC. CD = Crohn disease, UC = ulcerative colitis.