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Guidelines for Blood Test Monitoring of Methotrexate Toxicity in Juvenile Idiopathic Arthritis
OLIVA ORTIZ-ALVAREZ, KIMBERLY MORISHITA, GLENDA AVERY, JAYNE GREEN, ROSS E. PETTY, LORI B. TUCKER, PETER N. MALLESON, and DAVID A. CABRAL
ABSTRACT. Methods. Eighty-nine patients with JIA treated with MTX were monitored prospectively: aspartate aminotransferase (AST), alanine aminotransferase (ALT), complete blood count (CBC), and differential blood count were measured prior to starting MTX, and then monthly. Significantly abnormal blood tests (SABT) were prospectively defined as (1) significantly elevated liver enzymes (SELE) greater than twice the upper limit of normal; (2) granulocyte count < 1.5 ´ 109/l; (3) lymphocyte count < 0.9 ´ 109/l; or (4) hemoglobin decreased by > 2 g/l from previous level. Clinical interventions, current and cumulative MTX dose, duration of treatment, comorbidity, and concurrent medications at the time of the first SABT identification were recorded. Independent t tests and chi-squared tests were used for comparisons, and the probability of developing a SABT was calculated by Kaplan-Meier survival analysis. Results. Forty percent of patients had a SABT: 26% had hematological abnormalities and 14% had SELE. Ninety-five percent of patients with SABT had symptoms consistent with a viral infection when the SABT was drawn and MTX dose was withheld until results had normalized on repeat testing. SABT persisting beyond one month occurred in only 2 patients, and their abnormalities resolved by 6 months with no specific identified cause; they resumed MTX at a later time without recurrence of SABT. There were no differences between patients with and without SABT with respect to current or cumulative MTX dose, duration of treatment, and concurrent medications at the time of the SABT. The probability of developing a SABT was estimated to be 11% at 3 months, compared to 10% probability of having an abnormal blood test by chance alone. Conclusion. Routine blood tests every 4 to 8 weeks in children with JIA are unnecessarily frequent. (J Rheumatol 2004;31:2501-6) Key Indexing Terms:
JUVENILE IDIOPATHIC ARTHRITIS
From the Division of Rheumatology, Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada. Dr. Ortiz-Alvarez was supported in part by a grant from The Arthritis Society, BC and Yukon Division, Canada. O. Ortiz-Alvarez, MD, MSc, Clinical Research Associate; K. Morishita, Medical Student; G. Avery, RN; J. Green, RN; R.E. Petty, MD, PhD, Professor; L.B. Tucker, MD, Clinical Associate Professor; P.N. Malleson, MBBS, Professor; D.A. Cabral, MBBS, Clinical Associate Professor. Address reprint requests to Dr. D. Cabral, British Columbia's Children's Hospital, Room K4-119, 4480 Oak Street, Vancouver, BC V6H 3V4, Canada. E-mail: dcabral@cw.bc.ca Submitted February 12, 2004; revision accepted July 15, 2004. |