Treat early to beat Crohn's disease

Summarized by Susan Aldridge, PhD, medical journalist
March 28, 2008

Summary

Crohn's disease is usually managed by corticosteroid treatment, but this approach is not without problems for the patient. A study by Belgian and Dutch researchers now suggests that when immunosuppressive drugs are given early after diagnosis, the patient can look forward to a higher chance of remission and less need for corticosteroids.

Introduction

Crohn's disease is a chronic inflammatory disorder of the gastrointestinal tract. The conventional approach to its treatment involves tackling the inflammation with corticosteroids. But many patients will become either resistant to, or dependent on, steroids. Moreover, these drugs are linked to a complication called Cushing's syndrome which may increase mortality in the long run. So steroids alone are far from ideal, which is why many clinicians have been turning to immunosuppressive drugs, such as azathioprine - but they generally only use them once problems with steroids have set in.

Then there are the new tumor-necrosis factor (TNF) antagonists, such as infliximab (Remicade), otherwise known as biological therapies. Again these tend to be used later in the course of Crohn's, when patients have failed to respond to other treatments, although they have shown promise in the early treatment of rheumatoid arthritis, a related inflammatory condition. Meanwhile, combination therapy is proving its worth in many diseases and TNF administered with methotrexate, an immunosuppressant drug like azathioprine, was better in early rheumatoid arthritis than either drug alone. Accordingly, researchers for the Belgian Inflammatory Bowel Disease Research Group and the North-Holland Gut Club determined to check out some of these possibilities with a trial of early combined immunosuppression in patients newly diagnosed with Crohn's disease.

What was done

A group of 133 patients with Crohn's disease diagnosed within the previous four years and aged between 16 and 75 was selected, none of whom had been previously treated with corticosteroids, immunosuppressive drugs, or biological therapy. Sixty five of them received three infusions, at weeks 0, 2 and 6, of infliximab combined with azathioprine. The rest of the group received conventional treatment consisting of corticosteroids followed by azathiprine and infliximab. The researchers recorded remission of the disease without the need for either further corticosteroid treatment or surgery at weeks 26 and 52.

What was found

At week 26, 60 percent of those in the immunosuppression group were in remission, compared to 35.9 percent of those in the conventional treatment group. At week 52, the corresponding rates were 61.5 percent and 42.2 percent. Lab studies showed that combined immunosuppression promoted healing in the gastrointestinal mucosa, as well as decreasing levels of C-reactive protein, which is a measure of inflammation.

What this study means

Patients given combined immunosuppression in the form of azathioprine and infliximab did significantly better in terms of remission without the need for steroids and surgery. The immunosuppressive approach started early also seems to limit the pathology of the disease in terms of ulceration and inflammation, while protecting patients from the adverse effects of long-term steroid use. Therefore, the take-home message seems to be - in Crohn's, go in early and make treatment intensive.

Source

• Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn's disease: an open randomised trial. G. D'Haens, F. Baert,  et al., The Lancet, 2008, pp. 660--667

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