RITUXIMAB IN THE TREATMENT OF PATIENTS WITH DERMATOMYOSITIS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。皮肌炎是一种由肌肉和/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、嵌合、鼠/人单克隆抗体，针对在正常和恶性前B细胞和成熟B细胞表面发现的CD20抗原。本研究的目的是：1。评估使用利妥昔单抗选择性破坏B细胞是否会减轻皮肌炎的体征和症状。2. 确定利妥昔单抗治疗皮肌炎患者的安全性和耐受性。3. 探讨利妥昔单抗在该患者群体中的药代动力学和药效学（如b细胞耗竭持续时间的范围）。研究设计：这项前瞻性开放标签试验将招募8名皮肌炎患者。每个受试者将在研究用药前4周进行筛选评估。每位受试者将在第1天（基线治疗日）和第15天接受1000mg的利妥昔单抗静脉注射（IV），共两次输注。随访评估将在第4、8、12、16、20、24、36和48周进行。所有退出本研究的患者必须在退出研究之日起的第4、12、24、36和48周返回进行随访安全性评估。将收集所有停药患者的不良事件以及b细胞仍然耗尽的患者的淋巴细胞计数。48周后，每2个月应继续对B细胞仍未恢复的患者进行进一步随访，直到从退出研究之日起第4、12、24、36和48周对这些细胞进行评估。将收集所有停药患者的不良事件以及b细胞仍然耗尽的患者的淋巴细胞计数。48周后，每2个月随访一次B细胞减少的患者，直到B细胞恢复到原来的基线或正常水平。所有退出本研究的患者将被随访至少48周，或直到B细胞水平恢复到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 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.