The TAKEOFF Trial: Clinical Trial Planning Grant

TAKEOFF 试验：临床试验计划补助金

• 批准号: 8031114
• 负责人: JEFFREY R. CURTIS
• 金额: $ 14.65万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2012-08-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8031114
• 关键词: Anti-Tumor Necrosis Factor Therapy; Antirheumatic Agents; Arthritis; Biochemistry; Biological Markers; Biological Response Modifier Therapy; British; Clinic; Clinical; Clinical Trials; Combined Modality Therapy; Data; Data Analyses; Data Collection; Development; Disease; Disease remission; Disease-Modifying Second-Line Drugs; Dose; Drug Kinetics; Early treatment; Etanercept; Flare; Grant; Health; Hydroxychloroquine; Individual; Infection; Injection of therapeutic agent; Internal Medicine; Methotrexate; Outcome Measure; Patients; Pharmaceutical Economics; Pharmaceutical Preparations; Positioning Attribute; Prevalence; Process; Randomized; Research; Research Design; Rheumatoid Arthritis; Safety; Sales; Site; Source; Sulfasalazine; TNF gene; Testing; Therapeutic; Toxic effect; United States National Institutes of Health; Variant; adalimumab; arthritis therapy; cancer risk; clinical efficacy; clinical remission; cohort; cost; data management; disorder control; dosage; evidence base; follow-up; improved; indexing; infliximab; news; patient safety; response; rheumatologist

DESCRIPTION (provided by applicant): Anti-TNF drugs (adalimumab, certolizumab, etanercept, golimumab, infliximab) are commonly used with methotrexate (MTX) in rheumatoid arthritis (RA). Despite the development of these new and exciting biological therapies for the treatment of RA, their relatively high costs (< $24,000/year) and possible toxicities (infection, cancer risk, injection site problems) are drawbacks to their use. MTX remains an anchor drug for RA therapy; however, there is substantial unexplained variation in patient response to MTX therapy. It is unknown if anti- TNF drugs may ultimately be discontinued in individuals on dual therapy. The ability to taper an anti-TNF drug may depend on the ability to optimize MTX therapy or the addition of an additional disease modifying antirheumatic drugs (DMARD). We propose a clinical trial planning grant to convene an expert panel to refine the study design, outcome measures, data collection and data analysis for the TAKEOFF Trial (Optimizing Methotrexate and Discontinuing Anti-TNF Agents in RA). This study will test the hypothesis that among patients who have been in clinical remission (CDAI d 2.8) for at least 6 months, patients randomized to discontinue or reduce the dose of anti-TNF therapy with either concomitant optimization of MTX or addition of SSZ + HCQ will have a likelihood of continued remission that is non-inferior compared to patients randomized to continue anti-TNF therapy + MTX. The clinical trial planning process will involve experts related to RA trials planning, MTX biochemistry, outcome measures and data analysis. It is expected at the end of the planning process that an NIH grant will be submitted related to optimization discontinuing biological therapies.

描述（由申请方提供）：抗TNF药物（阿达木单抗、赛妥珠单抗、依那西普、戈利木单抗、英夫利昔单抗）通常与甲氨蝶呤（MTX）联合用于类风湿性关节炎（RA）。尽管开发了这些新的和令人兴奋的生物疗法用于治疗RA，但其相对较高的成本（<24，000美元/年）和可能的毒性（感染，癌症风险，注射部位问题）是其使用的缺点。MTX仍然是RA治疗的锚药;然而，患者对MTX治疗的反应存在大量无法解释的变化。目前尚不清楚是否抗肿瘤坏死因子药物可能最终停止在个人的双重治疗。逐渐减少抗TNF药物的能力可能取决于优化MTX治疗的能力或添加额外的疾病缓解抗风湿药物（DMARD）。我们提议提供临床试验计划补助金，以召集专家小组，完善TAKEOFF试验（优化RA中的甲氨蝶呤和停用抗TNF药物）的研究设计、结局指标、数据收集和数据分析。本研究将检验以下假设：在临床缓解（CDAI d 2.8）至少6个月的患者中，随机分配至抗TNF治疗中止或降低剂量并伴随MTX优化或添加SSZ + HCQ的患者与随机分配至继续抗TNF治疗+ MTX的患者相比，持续缓解的可能性非劣效于后者。临床试验规划过程将涉及与RA试验规划、MTX生物化学、结局测量和数据分析相关的专家。预计在规划过程结束时，将提交与优化停止生物疗法相关的NIH赠款。