Two new approaches to the treatment of Crohn's disease have been reported in the New England Journal of Medicine. The first found that a low dose of methotrexate maintained remission (2000;342:1627) and the second found that growth hormone may be of potential benefit for the treatment of the disease (2000;342:1633).
In the first study, 65 per cent of patients treated with methotrexate were in remission after 40 weeks compared with 39 per cent of the placebo group, according to Dr Brian Feagan (clinical trials research group, John P. Robarts institute, Ontario, Canada) and colleagues.
Patients with chronically active Crohn's disease who had entered remission following 16 to 24 weeks of treatment with weekly injections of 25mg metho-trexate were randomly assigned placebo or methotrexate. Forty patients received 15mg methotrexate intramuscularly weekly and 36 patients received placebo.
Patients in the methotrexate group had fewer relapses than the placebo group. Over the trial period, 72 per cent of patients in the methotrexate group did not need prednisolone treatment for recurrent symptoms compared with 42 per cent of the placebo group. The median duration of remission was 22 weeks in the placebo group but could only be determined as greater than 40 weeks in the methotrexate group because fewer than 50 per cent of patients had relapsed before the end of the 40-week study.
Following relapse, 22 patients were treated with 25mg methotrexate once weekly, usually in addition to prednisolone. Of these patients, 55 per cent were in remission by week 40 and had discontinued use of prednisolone. Of the 14 who did not receive post-relapse methotrexate, only 2 patients (14 per cent) were in remission at week 40.
In terms of adverse effects, Dr Feagan and colleagues say that the overall incidence was similar in both groups. None of the patients in the methotrexate group had a severe adverse event although nausea and vomiting occurred more frequently.
They conclude that methotrexate was "an effective and safe maintenance therapy" for patients with Crohn's disease. They comment that, in rheumatoid arthritis, methotrexate has been preferred to azathioprine because it has a more rapid effect and better long term tolerability but that the hepatic toxicity of methotrexate remains a concern.
In the second, more preliminary study, Dr Alfred Slonim (department of paediatrics, North Shore University hospital, New York, US) and colleagues investigated the use of growth hormone for Crohn's disease. Patients who received growth hormone had a significant improvement by the end of the first month and further improvements during the following months of the four-month trial compared with patients who received placebo. This led to a reduction in the amount of medication used for Crohn's disease.
Growth hormone was given by subcutaneous injection to 19 patients in a loading dose of 5mg per day for a week then 1.5mg daily. Eighteen patients received placebo and all patients were instructed to eat a high protein diet. The most frequent side effects of growth hormone therapy were oedema and headache. However, the authors say that a concern of administering growth hormone to adults is that it may induce tumours.
They comment: "Growth hormone enhances the uptake of amino acids and electrolytes by the intestines, decreases intestinal permeability and increases intestinal protein synthesis in animals." In addition, it enhances the beneficial effect of supplemental protein on the intestinal tract. They suggest that a larger study is now needed.