Dastmalchi M, Grundtman C, Alexanderson H, Mavragani C P, Einarsdottir H, Helmers S Barbasso, Elvin K, Crow M K, Nennesmo I, Lundberg I E
Rheumatology, Unit, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Solna, SE-171 76 Stockholm, Sweden.
Ann Rheum Dis. 2008 Dec;67(12):1670-7. doi: 10.1136/ard.2007.077974. Epub 2008 Feb 13.
To investigate the effect of the tumour necrosis factor (TNF) blocking agent infliximab in patients with treatment-resistant inflammatory myopathies.
A total of 13 patients with refractory polymyositis (PM), dermatomyositis (DM), or inclusion body myositis (IBM) were treated with 4 infliximab infusions (5 mg/kg body weight) over 14 weeks. Outcome measures included myositis disease activity score with improvement defined according to The International Myositis Assessment and Clinical Studies Group (IMACS), and MRI. Repeated muscles biopsies were investigated for cellular infiltrates, major histocompatibility complex (MHC) class I and II, TNF, interleukin (IL)1alpha, IL6, high mobility group box chromosomal protein 1 (HMGB-1), interferon gamma (IFNgamma), myxovirus resistance protein A (MxA) and membrane attack complex (MAC) expression. Type I IFN activity was analysed in sera.
Nine patients completed the study. Three patients discontinued due to adverse events and one due to a discovered malignancy. Three of the completers improved by >or=20% in three or more variables of the disease activity core set, four were unchanged and two worsened >or=30%. No patient improved in muscle strength by manual muscle test. At baseline, two completers had signs of muscle inflammation by MRI, and five at follow-up. T lymphocytes, macrophages, cytokine expression and MAC deposition in muscle biopsies were still evident after treatment. Type I IFN activity was increased after treatment.
Infliximab treatment was not effective in refractory inflammatory myopathies. In view of radiological and clinical worsening, and activation of the type I IFN system in several cases, infliximab is not an alternative treatment in patients with treatment-resistant myositis.
研究肿瘤坏死因子（TNF）阻断剂英夫利昔单抗对难治性炎性肌病患者的疗效。
13例难治性多发性肌炎（PM）、皮肌炎（DM）或包涵体肌炎（IBM）患者在14周内接受4次英夫利昔单抗输注（5 mg/kg体重）治疗。观察指标包括根据国际肌炎评估与临床研究组（IMACS）定义的肌炎疾病活动评分及改善情况，以及磁共振成像（MRI）。对重复的肌肉活检组织进行细胞浸润、主要组织相容性复合体（MHC）I类和II类、TNF、白细胞介素（IL）1α、IL6、高迁移率族蛋白B1（HMGB-1）、干扰素γ（IFNγ）、抗黏液病毒蛋白A（MxA）和膜攻击复合物（MAC）表达的研究。分析血清中的I型干扰素活性。
9例患者完成研究。3例患者因不良事件停药，1例因发现恶性肿瘤停药。3例完成研究的患者在疾病活动核心集的三个或更多变量中改善≥20%，4例无变化，2例恶化≥30%。通过徒手肌力测试，无患者肌肉力量得到改善。基线时，2例完成研究的患者MRI显示有肌肉炎症迹象，随访时有5例。治疗后肌肉活检中T淋巴细胞、巨噬细胞、细胞因子表达和MAC沉积仍然明显。治疗后I型干扰素活性增加。
英夫利昔单抗治疗难治性炎性肌病无效。鉴于在几例患者中出现影像学和临床恶化以及I型干扰素系统激活，英夫利昔单抗不是难治性肌炎患者的替代治疗方法。
