PIC QUESTION OF THE WEEK: 10/01/07 Q: Is methotrexate appropriate for the treatment of juvenile uveitis? A: Uveitis is a general term describing an inflammatory condition of the uveal tract, an area of the eye comprised of the iris, ciliary body, and choroid (middle layer of the eye between the retina and sclera). It may be chronic or acute and its etiologies may be infectious or non-infectious in nature. The condition may be observed in adults or children. Depending on the exact location, uveitis may be further classified as anterior, posterior, or intermediate. Infectious juvenile uveitis is frequently related to parasitic (e.g. toxoplasmosis), viral (e.g. influenza, mumps, measles etc), or bacterial (e.g. Lyme disease) organisms. Its treatment is based on appropriate antimicrobial selection and eradication of the causative organism. Non-infectious uveitis is most commonly associated with juvenile idiopathic arthritis (JIA; more commonly referred to as juvenile rheumatoid arthritis), Behcet disease, sarcoidosis, and Kawasaki disease. In some studies, JIA was identified in 41% - 67% of children with uveitis. Chronic pediatric uveitis is estimated to cause severe, life-long visual disabilities in 25% - 33% of those with the disease. Problems include cataracts, glaucoma, and band keratopathy. Chronic non-infectious uveitis has been treated with immunosuppressive drugs such as methotrexate and cyclosporine, cytotoxic agents (e.g. cyclosphosphamide), tumor necrosis factor (TNF) inhibitors, and non-steroidal antiinflammatory drugs. Methotrexate is the most common agent used in children with uveitis. Although methotrexate has not been evaluated in large, controlled, prospective trials, response rates are suggested to be approximately 60%. Dosage generally ranges from 10 – 30 mg/m2 once weekly. The drug is cleared more rapidly in children than adults, thus accounting for the relatively higher dosage. Gastrointestinal disturbances are the most frequent complication associated with methotrexate. These problems may be minimized by concurrent oral administration of folic acid. The most-serious adverse effects include hepatotoxicity, bone marrow toxicity, and interstitial pneumonitis. Subcutaneous administration is better tolerated and provides for greater bioavailability per dose administered. Another immunosuppressive agent, mycophenolate mofetil (Pro-Graf), is currently being evaluated for the treatment of chronic uveitis in children. It may be an appropriate alternative for those who cannot tolerate methotrexate. References: • • •
Kunimoto DY, Kanitkar KD, Makar MS. Uveitis. In: Kunimoto DY, Kanitkar KD, Makar MS, eds. The Wills Eye Manual. 4trd ed. Philadelphia, PA: Lippincott Williams Wilkins;2004:290-321. Holland GN, Stiehm ER. Special considerations in the evaluation and management of uveitis in children. Am J Ophthalmol 2003;135:867-78. Smith J.R.. Management of uveitis. Clin Exp Med 2004;3:21-9.
Amanda N. Kunkle and Peter A. Ponchione, Pharmacy Clerkship Students The PIC Question of the Week is a publication of the Pharmaceutical Information Center, Mylan School of Pharmacy, Duquesne University, Pittsburgh, PA 15282 (412.396.4600).