青少年特发性关节炎中甲氨蝶呤毒性血液检测监测指南。

Guidelines for blood test monitoring of methotrexate toxicity in juvenile idiopathic arthritis.

作者信息

Ortiz-Alvarez Oliva, Morishita Kimberly, Avery Glenda, Green Jayne, Petty Ross E, Tucker Lori B, Malleson Peter N, Cabral David A

机构信息

Division of Rheumatology, Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada.

出版信息

J Rheumatol. 2004 Dec;31(12):2501-6.

PMID:15570658

Abstract

OBJECTIVE

To assess the utility of the American College of Rheumatology guidelines for monitoring methotrexate (MTX)-related toxicity in a cohort of children with juvenile idiopathic arthritis (JIA).

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.

摘要

目的

评估美国风湿病学会指南在监测一组幼年特发性关节炎（JIA）患儿甲氨蝶呤（MTX）相关毒性方面的实用性。

方法

对89例接受MTX治疗的JIA患者进行前瞻性监测：在开始MTX治疗前及之后每月测量天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）、全血细胞计数（CBC）和分类血细胞计数。显著异常血液检查（SABT）被前瞻性定义为：（1）肝酶显著升高（SELE），高于正常上限两倍；（2）粒细胞计数<1.5×10⁹/L；（3）淋巴细胞计数<0.9×10⁹/L；或（4）血红蛋白较之前水平下降>2g/L。记录首次识别SABT时的临床干预措施、当前和累积MTX剂量、治疗持续时间、合并症及同时使用的药物。采用独立t检验和卡方检验进行比较，并通过Kaplan-Meier生存分析计算发生SABT的概率。

结果

40%的患者出现SABT：26%有血液学异常，14%有SELE。95%出现SABT的患者在进行SABT检查且停用MTX直至复查结果正常时，有与病毒感染相符的症状。仅2例患者SABT持续超过1个月，其异常在6个月时消失，未发现明确原因；他们后来恢复使用MTX，未再出现SABT。出现SABT和未出现SABT的患者在SABT时的当前或累积MTX剂量、治疗持续时间及同时使用的药物方面无差异。估计3个月时发生SABT的概率为11%，而仅因偶然出现血液检查异常的概率为10%。