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Azathioprine for maintenance of remission in Crohn's disease

  • Review
  • Intervention

Authors

  • DC Pearson,

  • GR May,

  • G Fick,

  • LR Sutherland


Dr Lloyd Sutherland, A902-500 Eau Claire Ave SW, Calgary, Alberta, T2P 3R8, CANADA. lsutherl@ucalgary.ca.

Abstract

Background

The therapeutic role of 6-mercaptopurine and azathioprine remains controversial due to their relatively slow-acting effect and adverse effects. A meta-analysis was performed to evaluate the efficacy of azathioprine in the maintenance of remission of quiescent Crohn's disease.

Objectives

To assess the effectiveness of azathioprine in maintaining remission of quiescent Crohn's disease.

Search strategy

Pertinent studies were selected using the MEDLINE data base (1966 - May 1998), the Cochrane Controlled Trials Register, the Inflammatory Bowel Disease Trials Register, as well as abstracts from major gastrointestinal research meetings and references from published articles and reviews.

Selection criteria

Five randomized, double-blind, placebo-controlled trials of azathioprine therapy were identified. Two of these trials consisted solely of patients with quiescent Crohn's disease. Three trials had multiple therapeutic arms for both induction of remission and maintenance of remission.

Data collection and analysis

Data were extracted by three independent observers (GRM, GF, LRS) based on the intention to treat principle. Peto odds ratios for the overall maintenance of remission, steroid sparing, and withdrawals due to adverse effects were calculated, and from these, 95% confidence intervals were derived. Numbers needed to treat or harm (NNT, NNH respectively) for the maintenance of remission, steroid sparing, and withdrawals due to adverse effects were also determined.

Main results

Azathioprine had a positive effect on maintaining remission. The Peto odds ratio for maintenance of remission was 2.16 (CI 1.35 - 3.47) with an NNT of 7. A higher dose improved response. A steroid sparing effect was noted, with a Peto odds ratio of 5.22 (CI 1.06 - 25.68) and NNT of 3 for quiescent disease. The Peto odds ratio for withdrawals due to adverse events was 4.36 (CI 1.63 - 11.67), the NNH (Number Needed to Harm) was 19.

Authors' conclusions

Azathioprine is effective in maintaining remission. There is evidence for a steroid sparing effect.

Plain language summary

Plain language summary

Azathioprine may be effective for maintaining remission in some patients with Crohn's disease but may, rarely, have serious side effects.

Azathioprine (1.0 to 2.5 mg/day) used among patients with non-active Crohn's disease may be effective for reducing the risk of disease recurrence over a 6 month to 2 year period. Higher doses of azathioprine (2.5 mg/day) are more effective than lower doses (1.0 or 2.0 mg/day) for preventing disease recurrence. There is also evidence that azathioprine reduces the need for steroid treatment which could help reduce steroid related side effects. However, since the studies were of short duration (6 months to 2 years) the long-term effectiveness of azathioprine is unclear. Azathioprine is a slow acting drug that is associated with some rare but serious side effects. These include suppression of the body's ability to produce white blood cells (which fight infection) and platelets (which allow blood clotting to occur), and inflammation of the pancreas. Patients who may benefit from this therapy include those whose Crohn's disease is chronically active or flares frequently. Azathioprine may also benefit patients who are dependent on steroids but have experienced steroid side effects, or for whom steroids no longer work. The choice to use azathioprine should be made after careful consideration of the risks and benefits of using the drug.

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