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 post-operative 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 5-aminosalicylates (5-ASA), 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. On network meta-analysis, compared with placebo, 5-ASA (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), immunomodulators 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), immunomodulators 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 5-ASA (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 pharmacological intervention for post-operative 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 post-operative prophylaxis for CD.

Effectiveness of Mesalazine, Thiopurines and Tumour Necrosis Factor Antagonists in Preventing Post-Operative Crohn's Disease Recurrence in a Real-Life Setting

“…This finding is in line with recent data showing that there is no correlation between clinical symptoms and endoscopic lesions [23,24,25,26]. Finally, a Bayesian network meta-analysis including 21 trials with 2,006 patients compared 7 treatment strategies and found that anti-TNF monotherapy was the most effective treatment for the prevention of post-operative CD recurrence [27]. …”

Editorial: predicting recurrence of Crohn's disease after surgical resection—close to a crystal ball

“…In addition, the investigators also identified that post‐operative prophylaxis with tumour necrosis factor (TNF)‐α antagonists was associated with 50% lower odds of endoscopic recurrence. This finding too was stable in a propensity score‐matched analysis, attesting to the efficacy of prophylactic therapy as previously demonstrated . Interestingly, they also observed that 8/10 TNF‐α antagonist‐treated patients with anti‐drug antibodies at the time of surgery experienced endoscopic recurrence, compared to 13/43 (30%) without anti‐drug antibodies.…”

The Microbiome and Cancer: Is the ‘Oncobiome’ Mirage Real?

“…Finally, increased carcinogenesis was noted after the enteral introduction of Fusobacterium nucleatum or enterotoxigenic Bacteroides fragilis , in Apc Min/+ mice confirming the effect of bacteria on cancer formation in vivo [47,61]. However, as opposed to IBD where antibiotic usage has shown some clinical effectiveness [62–64], no such clinical studies are available for CRC. Despite these data in favor of the oncobiome, the microbiota may also prevent carcinogenesis through protective mechanisms, detoxification, or anticancer metabolites [65–67].…”