METHOTREXATE IN THE TREATMENT OF JUVENILE RHEUMATOID ARTHRITIS AND OTHER PEDIATRIC RHEUMATIC AND NONRHEUMATIC DISORDERS

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The goal of treating juvenile rheumatoid arthritis (JRA) is to minimize discomfort, reduce disability, prevent joint destruction, and maximize physical, intellectual, social, and emotional growth and development. Medications for JRA have previously been limited to aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and slow-acting antirheumatic drugs (SAARDs). However, data regarding the efficacy of SAARDs and the safety and efficacy of immunosuppressive agents in JRA were scant. Thus, use of these medications in children was often guided by data from published studies of adults with rheumatoid arthritis (RA).

In the past 15 years, low-dose methotrexate (MTX) has become widely used for both RA and JRA. Often, MTX was initiated only in children who were refractory to traditional slow-acting agents such as d-penicillamine, hydroxychloroquine, gold salts, and sulfasalazine, or when azathioprine, cyclophosphamide, and chlorambucil were deemed ineffective or too dangerous. Methotrexate for JRA has since been shown to be safe and effective in retrospective studies, in clinical practice, and in controlled trials. It is now often the first agent selected in children with established JRA and is increasingly used in related pediatric rheumatic disorders and other chronic inflammatory conditions.

Section snippets

Early Studies

In 1983 and 1984, Truckenbrodt and Hafner 77 treated 950 children with JRA in a German Rheumatic Children's Hospital. Although many responded to NSAIDs and/or SAARDs, others also required prolonged high-dose corticosteroids, with associated intolerable side effects. Because azathioprine was reported to be efficacious in only 30% to 50% of cases of JRA 43 and the potential for malignancy was high with the alkylating agents, 4 these authors used MTX to treat 19 children with severe JRA (systemic

Bioavailability

Herman and co-workers 32 found that at steady state the average fraction of MTX present in the tissues is 39%, and the mean terminal half-life of MTX is 6.1 hours. However, the bioavailability of oral MTX is highly variable, and the influence of food is controversial. A recent study of healthy adult volunteers 39 showed that food delays peak MTX serum concentration by 30 minutes, but the extent of total absorption was the same after an overnight fast and after a high-fat breakfast. In adults

Dermatomyositis

Childhood dermatomyositis (CDM) has been successfully treated with corticosteroids for several decades, although incomplete responses, relapse after initial improvement, growth retardation, and other major toxicities may occur. Anecdotally and in our personal experience, MTX has been used for CDM recalcitrant to high-dose oral or intravenous pulse corticosteroids for at least 20 years. The most common indications have been (1) intolerable steroid side effects; (2) severe rash or mucositis

Psoriasis

Methotrexate has been used for the treatment of severe psoriasis in adults for more than 20 years; however, experience in childhood is limited. Kumar and colleagues 42 reported use of MTX in seven children, 3.5 to 16 years old (mean, 12.1), whose pretreatment psoriasis was present for 5 months to 5 years (mean, 2.2 years). Disease forms included psoriatic erythroderma in three patients, generalized pustular psoriasis in two, and recalcitrant psoriasis and psoriatic arthropathy in one each.

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    Address reprint requests to Bernhard H. Singsen, MD, MPH, Section of Pediatric Rheumatology, Department of Rheumatic and Immunologic Diseases, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195

    *

    Section of Pediatric Rheumatology, Department of Immunologic and Rheumatic Diseases, and the Division of Pediatrics, Cleveland Clinic Foundation (BHS), and the Combined Program in Pediatrics and Medicine, The MetroHealth Medical Center (RG), Cleveland, Ohio

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    Copyright © 1997 W. B. Saunders Company. Published by Elsevier Inc. All rights reserved.