RITUXIMAB IN THE TREATMENT OF PATIENTS WITH DERMATOMYOSITIS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 皮肌炎是由肌肉和/或皮肤炎症引起的自身免疫性疾病。越来越多的证据表明B细胞在皮肌炎中起致病作用。利妥昔单抗是一种基因工程的嵌合鼠/人单克隆抗体，针对正常和恶性前B细胞和成熟B细胞表面的CD 20抗原。本研究的目的是： 1.为了评估使用利妥昔单抗选择性破坏B细胞是否 减少皮肌炎的症状和体征。 2.确定利妥昔单抗治疗皮肌炎患者的安全性和耐受性。 3.探讨利妥昔单抗的药代动力学和药效学 在该患者人群中（例如，B细胞耗竭的持续时间程度）。 研究设计： 这项前瞻性开放标签试验将入组8例皮肌炎患者。每例受试者将在研究药物给药前4周内接受筛选评价。每例受试者将在第1天（基线治疗日）和第15天接受1000 mg剂量的利妥昔单抗静脉（IV）输注，共输注2次。将在第4、8、12、16、20、24、36和48周进行随访评价。所有退出本研究的患者必须在退出研究之日起第4、12、24、36和48周返回接受随访安全性评价。将收集所有退出研究的患者的不良事件以及保持B细胞计数的患者的淋巴细胞计数。 耗尽了第48周后，任何B细胞仍然耗竭的患者应继续每2个月进行一次进一步随访，直到这些细胞恢复到原始基线或正常水平。 患者退出 所有退出本研究的患者将接受至少48周的随访，或直至B细胞水平恢复至其原始基线或正常水平。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Dermatomyositis is an autoimmune disorder resulting from inflammation of the muscles and/or skin. Evidence has accumulated that B cells play a pathogenic role in dermatomyositis. Rituximab is a genetically engineered, chimeric, murine/human monoclonal antibody directed against the CD20 antigen found on the surface of normal and malignant pre-B and mature B-cells. The objectives of this study are: 1. To evaluate if selective destruction of B cells using Rituximab will reduce the signs and symptoms of dermatomyositis. 2. To determine the safety and tolerability of Rituximab therapy in patients with dermatomyositis. 3. To explore the pharmacokinetics and pharmacodynamics of Rituximab in this patient population (e.g. extent of duration of B-cell depletion). Study Design: This prospective open-label trial will enroll 8 patients with dermatomyositis. Each subject will undergo a screening evaluation up to 4 weeks prior to study drug administration. Each subject will receive Rituximab at a dose of 1000 mg intravenously (IV) on day 1 (baseline treatment day) and day 15 for a total of two infusions. Follow-up evaluations will be performed at weeks 4, 8, 12, 16, 20, 24, 36, and 48. All patients who withdraw from this study must return for follow-up safety evaluations at weeks 4, 12, 24, 36, and 48 from the date of withdrawal from the study. Adverse events will be collected in all withdrawn patients together with lymphocyte counts in those patients who remain B-cell depleted. After week 48, further follow-up visits every 2 months should continue in any patient who remains B-cell-depleted, until these cells have returned to their original baseline or normal levels. Patient Withdrawals All patients who withdraw from this study will be followed for a minimum of 48 weeks or until B-cell levels have returned to their original baseline or normal levels.