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


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


METHODS
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.


METHODS
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.


METHODS
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.


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.


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.
Doherty
Glen
G
Center for Inflammatory Bowel Disease, Beth Israel Deaconess Medical Center, Rabb/Rose 1, East, Brookline Ave, Boston, MA, USA, 02215.
Bennett
Gayle
G
Patil
Seema
S
Cheifetz
Adam
A
Moss
Alan C
AC
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D003424:Crohn Disease / Q000517:prevention & control* / Q000601:surgery; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D009593:Nitroimidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D011183:Postoperative Complications / Q000517:prevention & control*; D019936:Probiotics / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D055502:Secondary Prevention
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007166:Immunosuppressive Agents; D009593:Nitroimidazoles