Combination therapy for Crohn's disease

In clinical practice, many patients with Crohn's disease are likely to receive combination therapy with corticosteroids, a 5-ASA-containing drug, azathioprine or 6MP and possibly antibiotics. This largely reflects therapeutic destitution and the 'add on' approach which most of us adopt for patients whose disease is not responding and in whom surgery may not be appropriate. Clear evidence that combinations of these drugs are more effective than each alone is difficult to obtain from published trials. Both the NCCDS and ECCDS showed that corticosteroids were superior to sulphasalazine for treating active Crohn's disease, but a combination of steroids and sulphasalazine was no better than steroids alone. A similar result was obtained in a Dutch study which made a direct comparison between sulphasalazine (4-6 g daily) alone and sulphasalazine with prednisolone. Although patients receiving the combined therapy improved faster, there was no difference between the two groups by 16 weeks. Whether higher doses of mesalazine drugs in combination with steroids would be more effective has not been tested. The combination of steroids with azathioprine has produced variable results. Tn Germany, regardless of site of disease, patients did better on combined therapy than on steroids alone, but no such benefit was seen in South Africa. However, both studies were small and in practice azathioprine (or 6MP) is usually introduced while patients are already receiving corticosteroids. Cyclosporin and methotrexate are also usually given to patients on steroids in order to reduce the need for steroids. Cyclosporin has little, if any, benefit for Crohn's disease but methotrexate may be beneficial, especially in patients already receiving 20 mg or more of prednisolone. Antibiotic combinations have been tested in Crohn's disease, principally as anti-mycobacterial therapy, but no therapeutic advantage has been shown except in one study in which four antibiotics were combined. Anecdotal evidence suggests that metronidazole and ciprofloxacin are an effective combination, but this has not been tested in a randomized clinical trial.