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Risk-Benefit Assessment of Drugs Used in the Treatment of Inflammatory Bowel Disease

  • Review Article
  • Risk-Benefit Assessment
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Summary

Although the aetiology of inflammatory bowel disease remains elusive, many agents are available for the control of symptoms and inflammation. Knowledge of drug pharmacology, indications and side effects is essential to ensure the best possible clinical care while minimising toxicity and inappropriate use.

Sulfasalazine consists of sulfapyridine linked to mesalazine (5-aminosalicylic acid) via an azobond. Its use is indicated in the treatment of mild to moderately active ulcerative colitis and in the prevention of relapse in patients with quiescent disease. Patients with mild to moderate co-Ionic or ileocolonic Crohn’s disease also benefit from this drug, as do a proportion of patients with isolated small bowel disease. Sulfasalazine has not been uniformly effective in preventing relapse in Crohn’s disease, although many clinicians continue its use in patients who respond initially. A high incidence of side effects which limit therapy include intolerance, hypersensitivity reactions and impairment of male infertility.

The newer aminosalicylates offer targeted delivery of mesalazine to the bowel, with fewer side effects. Topical mesalazine has proved extremely effective in patients with distal ulcerative colitis; oral forms are effective in the treatment of mild to moderately active ulcerative colitis and in relapse. Both types appear to be effective in the treatment of Crohn’s disease, and possibly in preventing relapse. There is no current clinical advantage of one mesalazine preparation over another, nor is there an indication for their use in sulfasalazine-treated patients who have satisfactory response without adverse effects.

Corticosteroids are indicated for more severe disease activity where the aminosalicylates have limited efficacy — specifically to induce remission in patients with severe or refractory ulcerative colitis or Crohn’s disease. They should not be used to maintain disease remission or in the prevention of postoperative recurrence. Topical corticosteroids allow their local use in distal colitis with minimal systemic side effects. Long term use is limited by side effects, many of which are dose related, although alternate-day therapy may lessen the incidence.

Immunosuppressive agents are beneficial for the treatment of refractory inflammatory bowel disease unresponsive to other medications, and may also facilitate the withdrawal of steroids in refractory patients. Mercaptopurine has an added benefit in the treatment of Crohn’s disease fistulae; the role of cyclosporin in bowel disease has not been established and its use cannot currently be recommended. The potential toxicity of immunosuppressive agents warrants careful consideration of their use by both physician and patient.

Metronidazole is indicated for the treatment of mild to moderate Crohn’s disease, including perineal disease. Common side effects include peripheral neuropathy and nausea. Broad spectrum antibiotics have a similar role in Crohn’s disease but, in ulcerative colitis, should be used only for severe, transmural inflammation. All patients should be monitored for the development of antibiotic-associated colitis.

Empirical agents such as the anticholinergic and antidiarrhoeal drugs can be useful as ad-junctive therapy in patients with mild to moderate disease. They should not be used in severe disease, given their unpredictability and a high incidence of adverse effects.

Investigational agents such as lipoxygenase inhibitors, free radical scavengers, methotrexate, chloroquine, cromolyn, intravenous immunoglobulin, clonidine, and short-chain fatty acids have shown promise in early reports, and warrant further controlled trials before their role in the therapy of inflammatory bowel disease can be determined.

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  1. Section of Gastroenterology, Department of Medicine, University of Chicago Medical Center, 5841 South Maryland Avenue, Hospital Box 400, Chicago, Illinois, IL 60637, USA

    Stephen B. Hanauer & George Stathopoulos

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  1. Stephen B. Hanauer
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Hanauer, S.B., Stathopoulos, G. Risk-Benefit Assessment of Drugs Used in the Treatment of Inflammatory Bowel Disease. Drug-Safety 6, 192–219 (1991). https://doi.org/10.2165/00002018-199106030-00005

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