The TAKEOFF Trial: Clinical Trial Planning Grant

描述（由申请人提供）：抗tnf药物（阿达木单抗，certolizumab，依那西普，golimumab，英夫利昔单抗）通常与甲氨蝶呤（MTX）一起用于类风湿性关节炎（RA）。尽管这些新的和令人兴奋的治疗类风湿性关节炎的生物疗法的发展，其相对较高的成本（< $24,000/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。甲氨蝶呤仍然是类风湿性关节炎治疗的锚定药物；然而，患者对甲氨蝶呤治疗的反应存在大量无法解释的差异。目前尚不清楚抗肿瘤坏死因子药物最终是否会在双重治疗的个体中停止使用。逐渐减少抗肿瘤坏死因子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修饰抗风湿药物（DMARD）。我们提议一项临床试验计划拨款，召集一个专家小组来完善研究设计、结果测量、数据收集和数据分析的起飞试验（优化甲氨蝶呤和停用抗肿瘤坏死因子药物在RA）。本研究将检验这样一个假设，即在临床缓解（CDAI d 2.8）至少6个月的患者中，随机选择停止或减少抗tnf治疗剂量并同时优化MTX或添加SSZ + HCQ的患者与随机选择继续抗tnf治疗+ MTX的患者相比，持续缓解的可能性并不差。临床试验计划过程将涉及与RA试验计划、MTX生物化学、结果测量和数据分析相关的专家。预计在计划过程结束时，NIH将提交一份与优化停止生物疗法相关的拨款。

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.