Azathioprine is used as an adjunct for prevention of the rejection of kidney allografts. The drug is usually used in conjunction with other immunosuppressive therapy including local radiation therapy, corticosteroids, and other cytotoxic agents.
The maximum effectiveness of azathioprine occurs when the drug is administered during the induction period of the antibody response, starting either at the time of antigenic stimulation or within 2 days following. Under certain conditions of pretreatment with mercaptopurine, followed by an interval of at least 5 days before administration of the antigen and no subsequent treatment, a paradoxical enhancement of antibody formation has been observed. The effects of azathioprine and its active metabolite, mercaptopurine, may not be observed until several days after initiation of therapy and may persist for several days after clearance of the compounds is completed.
Azathioprine is used for the management of the signs and symptoms of rheumatoid arthritis in adults. Azathioprine is one of several disease modifying antirheumatic drugs (DMARDs) that can be used when DMARD therapy is appropriate. Nonsteroidal anti-inflammatory agents (NSAIAs), including aspirin, and/or corticosteroids may be continued when treatment with azathioprine is initiated. The manufacturers state that combined use of azathioprine and other DMARDS has not been studied and is not recommended.
Azathioprine has been used in the management of moderately to severely or chronically active Crohn's disease, and to maintain clinical remission in corticosteroid-dependent patients, and to provide benefit in patients with fistulizing Crohn's disease.
Azathioprine (e.g., 2-3 mg/kg daily) has been used in conjunction with corticosteroids to induce remission in patients with mildly to severely active refractory Crohn's disease; however, onset of action of azathioprine is slow and several months usually are required to achieve clinical response. Therefore, the role, if any, of azathioprine in the management of acute disease activity is uncertain. Azathioprine is used in patients with chronically active corticosteroid-dependent Crohn's disease. Results of several placebo-controlled trials indicate that azathioprine may be effective in maintaining remission in patients with corticosteroid-induced clinical remissions and in allowing reduction of oral corticosteroid therapy in corticosteroid-dependent patients. In several studies, frequency of relapse associated with azathioprine has been substantially lower than that associated with placebo. Results of long-term follow-up studies indicate that treatment with azathioprine may be effective for up to 4 years. Limited data indicate that relapse rates after 4 years of immunosuppressive therapy may be similar whether therapy has been maintained or discontinued; however, further larger studies are needed to confirm such data.
Azathioprine also has been found effective in the management of fistulizing Crohn's disease. Current clinical practice concerning use of azathioprine is based on a point analysis of 5 controlled trials in which fistula closure was considered a secondary end point and on several uncontrolled case studies. Data from these studies indicate that long-term (several years) therapy with azathioprine may be effective in the management of fistulizing Crohn's disease. However, because there currently are no controlled studies employing fistula closure as a primary end point, additional study is needed to more clearly establish efficacy.
Azathioprine (1.5-2 mg/kg daily) has been used effectively in pediatric patients with refractory or corticosteroid-dependent Crohn's disease. In these patients, therapy with azathioprine may result in improvement of disease symptoms and reduction of corticosteroid dosage, and frequency of hospitalization.
Risks and benefits of azathioprine therapy should be carefully considered in patients with inflammatory bowel disease, especially in adolescents and young adults with the disease. Cases of hepatosplenic T-cell lymphoma have been reported in patients receiving azathioprine for the management of inflammatory bowel disease.
(See Cautions: Malignancies and Lymphoproliferative Disorders.)