Comparative efficacy of pharmacologic interventions in preventing relapse of Crohn's disease after surgery: a systematic review and network meta-analysis

Abstract

Background & aims: There are several drugs that might decrease the risk of relapse of Crohn's disease (CD) after surgery, but it is unclear whether one is superior to others. We estimated the comparative efficacy of different pharmacologic interventions for postoperative prophylaxis of CD, through a network meta-analysis of randomized controlled trials.

Methods: We conducted a systematic search of the literature through March 2014. We identified randomized controlled trials that compared the abilities of mesalamine, antibiotics, budesonide, immunomodulators, anti-tumor necrosis factor α (anti-TNF) (started within 3 months of surgery), and/or placebo or no intervention to prevent clinical and/or endoscopic relapse of CD in adults after surgical resection. We used Bayesian network meta-analysis to combine direct and indirect evidence and estimate the relative effects of treatment.

Results: We identified 21 trials comprising 2006 participants comparing 7 treatment strategies. In a network meta-analysis, compared with placebo, mesalamine (relative risk [RR], 0.60; 95% credible interval [CrI], 0.37-0.88), antibiotics (RR, 0.26; 95% CrI, 0.08-0.61), immunomodulator monotherapy (RR, 0.36; 95% CrI, 0.17-0.63), immunomodulator with antibiotics (RR, 0.11; 95% CrI, 0.02-0.51), and anti-TNF monotherapy (RR, 0.04; 95% CrI, 0.00-0.14), but not budesonide (RR, 0.93; 95% CrI, 0.40-1.84), reduced the risk of clinical relapse. Likewise, compared with placebo, antibiotics (RR, 0.41; 95% CrI, 0.15-0.92), immunomodulator monotherapy (RR, 0.33; 95% CrI, 0.13-0.68), immunomodulator with antibiotics (RR, 0.16; 95% CrI, 0.04-0.48), and anti-TNF monotherapy (RR, 0.01; 95% CrI, 0.00-0.05), but neither mesalamine (RR, 0.67; 95% CrI, 0.39-1.08) nor budesonide (RR, 0.86; 95% CrI, 0.61-1.22), reduced the risk of endoscopic relapse. Anti-TNF monotherapy was the most effective pharmacologic intervention for postoperative prophylaxis, with large effect sizes relative to all other strategies (clinical relapse: RR, 0.02-0.20; endoscopic relapse: RR, 0.005-0.04).

Conclusions: Based on Bayesian network meta-analysis combining direct and indirect treatment comparisons, anti-TNF monotherapy appears to be the most effective strategy for postoperative prophylaxis for CD.

Keywords: Comparative Effectiveness; Crohn’s Disease; Network Meta-Analysis; Postoperative Prophylaxis.

Figure 1

Flow sheet summarizing study identification and selection.

Figure 2

Evidence network of different pharmacological intervention for post-operative prophylaxis against clinical relapse of Crohn’s disease included in the network meta-analysis. Please note that two of the included RCTs were three-arm trials. The numbers (and numbers in brackets) refers to the number of trials (and number of combined number of participants in these trials), and the thickness of the connecting line corresponds to the number of trials between comparators.

Figure 3

Standard pair-wise meta-analysis of different pharmacological interventions for the prevention of (A) clinical relapse and (B) endoscopic relapse, for post-operative prophylaxis of Crohn’s Disease. Forest plots represent only comparisons for which >1 trial was available. Please note that in the forest plot, ‘experimental’ refers to first treatment group, whereas ‘control’ refers to the second treatment group.

Figure 3

Standard pair-wise meta-analysis of different pharmacological interventions for the prevention of (A) clinical relapse and (B) endoscopic relapse, for post-operative prophylaxis of Crohn’s Disease. Forest plots represent only comparisons for which >1 trial was available. Please note that in the forest plot, ‘experimental’ refers to first treatment group, whereas ‘control’ refers to the second treatment group.