Interventions for prevention of post-operative recurrence of Crohn's disease

Crohn's disease is a chronic illness where patients suffer from diarrhea, weight loss or stomach pain resulting from inflammation in the intestine. The illness often requires patients to undergo surgery in order to remove inflamed segments of intestine, but inflammation frequently returns at the site of surgery. This review examines the results of published studies which have looked at the effect of using medication following surgery for Crohn's disease as a mean of preventing the return (recurrence) of inflammation. Where possible, the results of studies were combined to compare the results of different treatments. A number of medications appeared to reduce the recurrence of inflammation, including metronidazole, mesalamine, azathioprine, 6-mercaptopurine and infliximab. Given that some of these medications have significant side-effects, the decision to use them requires a careful balancing of the risks and benefits for each individual patient

Authors' conclusions: 

There are insufficient randomised controlled trials of infliximab, budesonide, tenovil and interleukin-10 to draw conclusions. Nitro-imidazole antibiotics, mesalamine and immunosuppressive therapy with azathioprine/6-MP or infliximab all appear to be superior to placebo for the prevention of post-operative recurrence of Crohn's disease. The cost, toxicity and tolerability of these approaches require careful consideration to determine the optimal approach for post-operative prophylaxis.

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Background: 

Recurrence of Crohn's disease is common after intestinal resection. A number of agents have been studied in controlled trials with the goal of reducing the risk of endoscopic or clinical recurrence of Crohn's disease following surgery.

Objectives: 

To undertake a systematic review of the use of medical therapies for the prevention of post-operative recurrence of Crohn's disease

Search strategy: 

MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched to identify relevant studies. References from selected papers and abstracts from Digestive Disease Week were also searched.

Selection criteria: 

Randomised controlled trials that compared medical therapy to placebo or other medical agents for the prevention of recurrence of intestinal Crohn's disease were selected for inclusion.

Data collection and analysis: 

Two authors reviewed all abstracts containing search terms, and those meeting inclusion criteria were selected for full data abstraction. Dichotomous data were summarised using relative risk and 95% confidence intervals. A fixed-effects model was used, and sensitivity analysis performed.

Main results: 

Twenty-three studies were identified for inclusion. Probiotics were not superior to placebo for any outcome measured. The use of nitroimidazole antibiotics appeared to reduce the risk of clinical (RR 0.23; 95%CI 0.09 to 0.57, NNT=4) and endoscopic (RR 0.44; 95%CI 0.26 to 0.74, NNT = 4) recurrence relative to placebo. However, these agents were associated with higher risk of serious adverse events (RR 2.39, 95% CI 1.5 to 3.7). Mesalamine therapy was associated with a significantly reduced risk of clinical recurrence (RR 0.76; 95% CI 0.62 to 0.94, NNT = 12), and severe endoscopic recurrence (RR 0.50; 95% CI 0.29 to 0.84, NNT = 8) when compared to placebo. Azathioprine/6MP was also associated with a significantly reduced risk of clinical recurrence (RR 0.59; 95% CI 0.38 to 0.92, NNT = 7), and severe endoscopic recurrence (RR 0.64; 95% CI 0.44 to 0.92, NNT = 4), when compared to placebo. Neither agent had a higher risk than placebo of serious adverse events. When compared to azathioprine/6MP, mesalamine was associated with a higher risk of any endoscopic recurrence (RR 1.45, 95% CI 1.03 to 2.06), but a lower risk of serious adverse events (RR 0.51; 95% CI 0.30 to 0.89). There was no significant difference between mesalamine and azathioprine/6MP for any other outcome.

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