Adjuvant post-operative therapy

About 90% of patients with Crohn's disease require surgery at some time in their lives but the clinical recurrence rate after surgery is about 50% within 5 years, with 50% requiring further surgery within 10 years. Endoscopic evidence of relapse can be found in 75% within 12 weeks of resection. There is therefore a major problem to be solved. The solution is less clear. Retrospective studies suggest that smoking is a major factor determining a poor prognosis after surgery and it is most important that patients are encouraged to stop. There is strong evidence linking diet with Crohn's disease but the mechanism and nature of this link remains unclear. A low total fat intake, possibly supplemented with eudragit-coated n-3 fatty acid (fish oil) looks reasonable on current evidence but not proven. Mesalazine and metronidazole are the drugs for which most supportive evidence is available. The individual trials of mesalazine have generally proved inconclusive and meta-analyses have been needed to demonstrate a significant beneficial effect (approximately halving the relapse rate at 1 year). More recent large controlled studies performed after the meta-analyses however have again proved negative and the benefit is probably more modest than the meta-analyses suggested. Metronidazole, 20 mg/day for the first 3 months after surgery, has been shown to reduce relapse by just over one-third with a beneficial effect that was surprisingly sustained throughout a 3 year follow-up period. Peripheral neuropathy is a problem and further studies are needed at lower dosage. Azathioprine, 1.5-2 mg/kg/day is effective as maintenance therapy but there is insufficient evidence to recommend its routine post-operative use, moreover it takes up to 3 months to have an effect. Although budesonide has been shown to delay the time to relapse in nonoperated patients it, like other corticosteroids, has been shown to be no better than placebo when maintenance is assessed according to the proportion of patients who remain relapse-free after 1 year. Patients undergoing operation for Crohn's disease should therefore be strongly advised to stop smoking. A 3 month course of oral metronidazole plus continued maintenance with oral mesalazine can be justified on current evidence but further studies are needed.