Adams E M, Pucino F, Yarboro C, Hicks J E, Thornton B, McGarvey C, Sonies B C, Bartlett M L, Villalba M L, Fleisher T, Plotz P H
Arthritis Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
J Rheumatol. 1999 Feb;26(2):352-60.
To study the effects of the adenine analog, fludarabine, on patients with refractory dermatomyositis and polymyositis, and to assess variables used in following myositis patients during medical intervention.
Patients whose myositis was not controlled by prednisone and at least one other immunosuppressive medication were entered into a pilot study during which they received 6 monthly cycles of intravenous fludarabine. Patients were assessed at baseline, every other month, and at month 7 for primary outcome measures of strength and function. Other measurements including peripheral blood cell subsets, muscle enzymes, and various assessments of disease activity were followed monthly during the fludarabine infusion period and for up to 6 months post therapy.
Of 16 patients who entered the study, 4 patients were classified as improved, and 7 patients were classified as unchanged. Five patients who withdrew before month 7 were classified as treatment failures. Fludarabine caused a significant and prolonged lymphopenia without an increase in infectious complications over that seen with other immunosuppressive agents used for myositis. A sudden death of one patient at the end of the study was not thought to be drug related. Variables followed during the study emphasized the distinction between patient functional improvement and disease remission.
A subset of patients with refractory myositis may benefit from fludarabine therapy and controlled trials are indicated. Refinement and validation of variables useful for following myositis patients await larger studies.
研究腺嘌呤类似物氟达拉滨对难治性皮肌炎和多发性肌炎患者的疗效，并评估在医学干预期间用于跟踪肌炎患者的各项变量。
肌炎未被泼尼松及至少一种其他免疫抑制药物控制的患者进入一项试点研究，在此期间他们接受6个每月周期的静脉注射氟达拉滨治疗。在基线、每隔一个月以及第7个月对患者进行评估，以测量力量和功能等主要结局指标。在氟达拉滨输注期间每月跟踪其他测量指标，包括外周血细胞亚群、肌肉酶以及疾病活动的各种评估指标，治疗后长达6个月也进行跟踪。
进入研究的16例患者中，4例患者分类为病情改善，7例患者分类为病情未变。在第7个月前退出的5例患者分类为治疗失败。氟达拉滨导致显著且持久的淋巴细胞减少，与用于肌炎的其他免疫抑制剂相比，感染并发症并未增加。研究结束时1例患者突然死亡，认为与药物无关。研究期间跟踪的变量强调了患者功能改善和疾病缓解之间的区别。
一部分难治性肌炎患者可能从氟达拉滨治疗中获益，需要进行对照试验。用于跟踪肌炎患者的变量的完善和验证有待更大规模的研究。
