Clinical management

Since Crohn’s disease is considered an immune-mediated pathology, treatment has been geared toward attenuating the immune response. The disease is incurable but manageable.2

Historically, prednisone has been the initial agent of choice, followed by aminosalicylates (e.g., sulfasalazine) and such newer agents as mesalamine. If these fail, immunosuppressives (e.g., mercaptopurine and methotrexate) are used, followed by biologics (e.g., infliximab and adalimumab).22 This bottom-up approach is being challenged by some experts who advocate a top-down approach in which biologics and immunosuppressives are first-line therapy.


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Corticosteroids Prednisone and other corticosteroids have long been used to manage moderate-to-severe exacerbations of Crohn’s disease.22

While these agents are generally effective, long-term use is known to result in adverse effects, such as diabetes mellitus, bone demineralization, and poor wound healing. In addition, steroids have poor efficacy in maintaining remission.22 Oral doses of 40-60 mg are typically used, and the dose tapered off when the patient is in remission.2,22 In severe cases, hospitalization with bowel rest and IV steroids can be necessary.2

Budesonide, a relatively nonsystemic steroid, has been approved for mild-to-moderate disease of the ileum and ascending colon.22 The advantage is little (if any) suppression of the hypothalamic-pituitary-adrenal axis.

Aminosalicylates Sulfasalazine, a combination of sulfapyridine and mesalamine, has long been used in the management of Crohn’s disease (particularly colonic disease).12 Prescribe 3-5 g/day in divided doses.12 This agent is also effective in managing peripheral arthritis associated with a flare.19 Because sulfasalazine inhibits folic-acid absorption, supplementation should be given concurrently.12

Side effects of sulfasalazine (e.g., headache, nausea, vomiting, and rash) seem to be a result of the sulfa portion of the drug; mesalamine exerts the therapeutic effects. Consequently, newer formulations containing only mesalamine have been introduced. Asacol and Balsalazide are available for colonic disease and Dipentum and Pentasa for small-bowel disease. Mesalamine enemas and suppositories are available as topical therapy for rectal disease.

Immunosuppressives Chronic, steroid-dependent disease is treated with such immunosuppressive agents as mercaptopurine (75-125 mg daily, maximum dose 1.5 mg/kg/day) and azathioprine (150-250 mg daily, maximum dose 2.5 mg/kg/day).12 A limitation of these agents is that they often take up to nine months to exert their full effect.12 Consequently, they are not effective for acute flares but indicated for long-term remission.

Newer diagnostics have made potentially life-threatening consequences (e.g., neutropenia and hepatotoxicity) of these agents easier to predict and monitor. Both agents are metabolized by the enzyme thiopurine methyltransferase (TPMT), which produces two active metabolites, 6-thioguanine nucleotides and 6-methyl-mercaptopurine ribonucleotides.23 Low levels of TPMT, as well as high levels of either metabolite, may lead to toxicity, which can be life-threatening. TPMT levels can now be measured prior to treatment, as can metabolite levels during treatment, to ensure maximum efficacy and minimize the risks of leukopenia and hepatotoxicity.23 While these are useful tools to enhance patient safety, many insurers have not been willing to cover the cost of testing.

Pancreatitis has been reported with these immunosuppressives. It usually occurs within the first month of treatment and presents with abdominal pain, nausea, vomiting, and elevated amylase and lipase.2 If pancreatitis occurs, the agent should be discontinued. There is also a potential risk of lymphoma. 2 Cyclosporine and methotrexate are less commonly used immunosuppressive agents.

Biologics The newest options in the management of Crohn’s disease are the anti-tumor necrosis factor (TNF)-a agents infliximab and adalimumab. TNF-a is highly active in the inflammatory response in many diseases, including Crohn’s and rheumatoid arthritis.22

Inhibiting its action has proven to be effective in the long-term management of Crohn’s disease, including disease complicated by fistulas.22 Infliximab is delivered via periodic IV infusion, and adalimumab has the convenience of subcutaneous injection every two weeks.

A major side effect is infusion reaction, which is considered secondary to an immune-mediated process. Concurrent use of immunosuppressives, such as mercaptopurine, is thought to minimize this.22 Headache, nausea, and upper respiratory infections have been reported. There is also a potentially higher risk of lymphoma.22 Additionally, latent TB can become active with the use of these agents. A TB test is mandatory prior to treatment.

Antibiotics Such antibiotics as metronidazole and ciprofloxacin have inconsistently shown benefit in the management of mild-to-moderate Crohn’s disease.22 The reason is unknown. Antibiotic therapy has been successfully utilized for the treatment of abscesses and fistulas.

 

Mr. Askey is a certified registered nurse practitioner in the Department of Hepatology/Gastroenterology at the Guthrie Clinic in Sayre, Pa., and a contributing editor to The Clinical Advisor.

 

References

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