PULSE THERAPY IN SYSTEMIC JUVENILE RHEUMATOID ARTHRITIS

全身性幼年类风湿性关节炎的脉冲疗法

• 批准号: 2728347
• 负责人: DANIEL Joe LOVELL
• 金额: $ 7.25万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 2001-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2728347
• 关键词: adolescence (12-20); child (0-11); clinical research; clinical trials; combination chemotherapy; cyclophosphamide; drug adverse effect; human subject; human therapy evaluation; juvenile rheumatoid arthritis; methotrexate; methylprednisolone; nonsteroidal antiinflammatory agent; pharmacokinetics; prednisone; remission /regression; skeletal disorder chemotherapy

DESCRIPTION (adapted from applicant's abstract): Systemic juvenile rheumatoid arthritis (sJRA) is associated with significant long term morbidity and mortality. Current therapies including methotrexate are considered ameliorative rather than remission inducing or curative. There have been anecdotal reports suggesting that pulse therapy with intravenous corticosteroids, cyclophosphamide, and methotrexate may induce prolonged remissions in sJRA. Therefore, the objectives of this study are to determine and compare the ability of two pulse therapy regimens to induce remission in sJRA of less than 12 months duration during a 9-month, open-label, randomized, actively controlled clinical trial. The first pulse therapy regimen is composed of intravenous methylprednisalone 30 mg per kg per day (1 gram max) for three consecutive days, intravenous cyclophosphamide 0.4 grams per meter2 BSA on the third day, and up to 20 mg per meter2 per week of methotrexate. The second pulse therapy regimen is identical to the first, except no cyclophosphamide is given. Up to five cycles of these regimens may be given over a 9-month period. Patients in both groups may also receive background medications including a non-steroidal, anti-inflammatory drug and up to 0.5 mg/kg/d of oral prednizone. The primary outcome to measure the effect of this therapy will be the proportion of patients who achieve clinical remission according to the ACR criteria for remission in rheumatoid arthritis. Secondary outcome measures of effectiveness include proportion of patients who demonstrate clinical response according to the preliminary definition of improvement for JRA. In addition, time per remission and the duration of remission will be compared between the two groups among patients who do remit. Specific Aim 2 is to determine and compare the short and intermediate term (18 months) safety profiles of the pulse therapy regimens as defined in Specific Aim 1. Long term goals of the project are to determine and compare the longer-term safety profiles of this treatment regimen. This will involve analysis of patient/parent-derived data obtained by mail or phone follow-up to detect significant medical problems and reproductive or neoplastic complications.

描述（改编自申请人的摘要）：系统少年 类风湿关节炎（SJRA）与长期显着相关 发病率和死亡率。 包括甲氨蝶呤在内的当前疗法是 被认为是改善而不是诱导或治愈的。 那里 已经是轶事报告，表明静脉注射脉冲治疗 皮质类固醇，环磷酰胺和甲氨蝶呤可能会诱导延长 SJRA的恢复。 因此，这项研究的目标是 确定并比较两种脉冲治疗方案诱导的能力 在9个月期间，SJRA的持续时间不到12个月， 开放标签，随机，主动控制的临床试验。 第一个脉冲 治疗方案由静脉内甲基泼尼松龙每公斤30毫克组成 每天连续三天（1克最大）连续三天静脉注射 环磷酰胺第三天每米2 BSA 0.4克，最多20 mg 每周甲氨蝶呤每周2。 第二脉冲治疗方案是 除非没有环磷酰胺，否则与第一个相同。 最多五个 这些方案的周期可以在9个月内给出。 患者 两组也可能会收到背景药物 非甾体类，抗炎药，口服高达0.5 mg/kg/d 泼尼松。 衡量该疗法影响的主要结果将是 根据ACR获得临床缓解的患者比例 类风湿关节炎缓解的标准。 次要结果度量 有效性包括证明临床的患者的比例 根据JRA改进的初步定义的响应。 在 补充，每次缓解时间和缓解持续时间将被比较 在两组之间，这两组的患者屈服。 具体目标2是确定和比较短期和中间项 （18个月）脉冲治疗方案的安全概况 特定目标1。项目的长期目标是确定和比较 该治疗方案的长期安全概况。 这会 涉及分析通过邮件或电话获得的患者/父母衍生数据 随访以发现重大的医疗问题和生殖或 肿瘤并发症。