Outcomes in Rheumatic Diseases

风湿性疾病的治疗结果

• 批准号: 8746504
• 负责人: Michael Ward
• 金额: $ 103.5万
• 依托单位: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8746504
• 关键词: Accounting; Algorithms; Ankylosing spondylitis; Area; Arthritis; Attenuated; Benchmarking; Biomechanics; Body Height; Candidate Disease Gene; Cardiovascular Diseases; Caring; Characteristics; Chronic; Clinical; Clinical Treatment; Clinical Trials; Colorectal Cancer; Communities; Data; Data Analyses; Data Collection; Development; Disease; Disease remission; Dose; Double-Blind Method; End stage renal failure; Enrollment; Event; Fracture; Future; Genes; Genetic; Genetic Determinism; Genetic screening method; Genotype; Geographic Locations; Goals; HLA-B27 Antigen; Health; Health Personnel; Health Services Accessibility; Healthcare; Height; Hemorrhage; Hip Fractures; Hip region structure; Image; Impairment; Incidence; Infection; Intervertebral disc structure; Joints; Literature; Lupus Nephritis; Lymphoma; Magnetic Resonance Imaging; Malignant Neoplasms; Measurement; Measures; Mechanical Stress; Medicare; Meta-Analysis; Methods; Methotrexate; Nail plate; Observational Study; Orthopedic Surgery procedures; Orthopedics; Osteogenesis; Outcome; Outcome Measure; Pain; Paper; Patient Self-Report; Patients; Performance; Perioperative; Peripheral; Persons; Pharmaceutical Preparations; Phenotype; Physical Function; Placebo Control; Predisposition; Prednisone; Process; Property; Provider; Questionnaires; Regulation; Relapse; Reporting; Research; Review Literature; Rheumatism; Rheumatoid Arthritis; Risk; Risk Estimate; Sampling; Scanning; Self Assessment; Severities; Site; Socioeconomic Status; Spinal Fractures; Spinal Fusion; Statistical Methods; Structure; Subtrochanteric Fractures; Sulfasalazine; Symptoms; Systemic Lupus Erythematosus; Techniques; Testing; Time; Ultrasonography; Underrepresented Minority; United States National Institutes of Health; Withdrawal; Withdrawing Treatments; Woman; Work; X-Ray Computed Tomography; base; beneficiary; bisphosphonate; bone; burden of illness; calcification; cardiovascular risk factor; clinical epidemiology; clinical remission; computerized; cost; follow-up; functional disability; gene interaction; health disparity; high risk; instrument; men; mortality; preference; prospective; racial/ethnic difference; response; social; socioeconomics; spine bone structure; tool; trend; tumor necrosis factor-alpha inhibitor; vertebra body

Nine separate projects related to outcomes of patients with rheumatic diseases are included in this report. The first project, Genetic determinants of ankylosing spondylitis severity, is a prospective observational study of 1200 subjects with ankylosing spondylitis (AS) that seeks to identify genetic determinants of AS susceptibility and severity. This project will test genotype-phenotype correlations in a large sample. Over 1200 subjects have been enrolled at five centers including the NIH Clinical Center, and genetic testing and data analysis are underway. Radiographic data have been analyzed on 801 patients. Findings include 26 new genes associated with susceptibility to AS, gene-gene interaction between HLA-B27 and ERAP1 in risk of AS, impact of hip arthritis on physical functioning, lessening of association between radiographic damage and functional impairment with more prolonged AS, added value of using the Health Assessment Questionnaire to measure function in patients with peripheral joint arthritis, and association of ESR and CRP with axial impairments. Collaborators include Drs. J. Reveille, M. Brown, M. Weisman, J. Davis, T. Learch, and J. Malley. Ongoing work will test associations between several candidate genes involved in bone formation and regulation and the extent of radiographic damage. The second project, Progression of spinal fusion in ankylosing spondylitis, is a developmental study to test a measure of spinal fusion in AS based on quantification of calcification of the lumbar intervertebral discs by computed tomography. Thirty-eight subjects have been enrolled, and 33 have completed follow-up scans at 1 and 2 years. Nine subjects have completed studies testing the short-term reliability of measurements. Computerized semi-automatic algorithms for measuring syndesmophyte volume and height have been optimized to maximize reliability. Based on the three-dimensional information provided by these scans, we have discovered that syndesmophytes are non-randomly distributed around the vertebral rim, with preferential formation at the posteriolateral areas. This localization coincides with areas of high mechanical stress and suggests that biomechanics are likely under-recognized factors in syndesmophyte development. We have also developed this method to measure vertebral body height and disk height, which may be useful for precise measurement of vertebral fractures and disk disease. Collaborators on this project are Drs. J. Flynn, L. Yao, Y. Yao, and S. Tan. The third project, Clinically important changes in rheumatoid arthritis, is a prospective observational study of clinically important changes in rheumatoid arthritis (RA) activity. Current criteria for improvement in RA have not emphasized the patients perspective. The goals of this project are to identify benchmarks of important improvement in pain, functioning, and global arthritis status in RA based on the self-assessment by patients of changes in their symptoms. A future goal is to examine the measurement properties of preference measures. To date, 262 patients have been enrolled, and data collection completed on 250 patients. Results indicate patients are consistent in the degree of improvement necessary to be appreciated as an important change, and criteria for improvement have been determined for pain, physical functioning, patient global assessment, and four composite measures of RA activity. We also determined that clinical trial response criteria, such as the ACR20, are quite sensitive, but not specific, measures of improvement. The fourth project, Measurement of physical functioning, uses secondary analysis of clinical trial and observational data to understand which aspects of functioning are being measured in commonly used self-report instruments. We have found that performance measures are neither sensitive nor specific indicators of self-reported functional limitations. We have also found that, contrary to much previous literature, women and men have similar levels of self-reported functional limitations. In addition, we found no racial/ethnic differences in functional limitations after adjustment for measures of disease burden, although large differences by socioeconomic status remained despite adjustment for disease burden. The fifth project, Outcomes in patients with rheumatoid arthritis, uses secondary data to examine risks of mortality, malignancy and cardiovascular disease between patients with RA and those without RA. We have found the perioperative risk of cardiovascular events and mortality not to be increased among persons with rheumatoid arthritis. We are planning a study of trends in risk of colorectal cancer and lymphoma in patients with rheumatoid arthritis, which may vary with changes in the treatments used over time. The sixth project, Treatment-related outcomes in rheumatoid arthritis, uses primary data to examine if particular disease-modifying medications are associated with higher- or lower-than- expected risks of mortality, using advanced statistical methods to account for differential prescribing of more serious medications to sicker patients. We have found that methotrexate is associated with a substantial survival benefit, not attributable to channeling or selective medication use. We also found that low-dose prednisone use was associated with higher risk of mortality, but that this risk was attenuated by concomitant use of disease-modifying medications (methotrexate or sulfasalazine). We are also examining if differential access by patients of higher socioeconomic status to more effective anti-rheumatic medications over the past 25 years has resulted in the widening of socioeconomic disparity in health over time. The goals of the seventh project, Clinical epidemiology of systemic lupus erythematosus, are to investigate health disparities among patients with SLE, and to identify clinical features and health care practices that are associated with health outcomes. We have completed a systematic literature review of risk of end-stage renal disease in patients with lupus nephritis, identifying 161 papers that report these risks. We are now completing a Bayesian meta-analysis of these data to estimate risks of end-stage renal disease by treatment era and world geographic region. The goal of the eighth project, Outcomes in Orthopedics, is to investigate associations between processes and outcomes of orthopedic care. Initial studies have focused on time trends in the incidence of subtrochanteric fractures, using secondary data. Increases in incidence over time in the U.S. have paralleled increased use of bisphosphonate. Also the risk of atypical hip fractures was associated with degree of compliance with bisphosphonate treatment among Medicare beneficiaries. We conducted an observational study examining the association between chronic bisphosphonate use and subtrochanteric beaking, the radiographic precursor of subtrochanteric fracture. We found no difference in subtrochanteric beaking and chronic bisphosphonate use, indicating that this bone change is not an inevitable consequence of treatment. We have also examined differences in outcomes in fracture care related to use of either nails or plates, and have identified perioperative bleeding as a risk for operative site infection. The goal of the ninth project is to test whether patients with RA in clinical remission can safely be withdrawn from treatment with tumor necrosis factor-alpha inhibitors without having relapse of their arthritis. We have initiated a multicenter double-blind placebo-controlled withdrawal trial to test this hypothesis in 300 patients with RA in remission. This study will also provide data on clinical, imaging (joint ultrasound and magnetic resonance imaging), and immunological predictors of relapse.

本报告包含九个与风湿病患者结局相关的独立项目。第一个项目“强直性脊柱炎严重程度的遗传决定因素”是一项对 1200 名强直性脊柱炎 (AS) 受试者进行的前瞻性观察性研究，旨在确定强直性脊柱炎易感性和严重程度的遗传决定因素。该项目将在大样本中测试基因型-表型相关性。包括 NIH 临床中心在内的 5 个中心已招募了超过 1200 名受试者，基因检测和数据分析正在进行中。对 801 名患者的放射线数据进行了分析。研究结果包括与 AS 易感性相关的 26 个新基因、HLA-B27 和 ERAP1 之间的基因相互作用与 AS 风险、髋关节炎对身体功能的影响、随着 AS 时间延长，放射学损伤和功能损伤之间的关联性减弱、使用健康评估问卷测量外周关节关节炎患者功能的附加价值，以及 ESR 和 CRP 与轴损伤的关联。合作者包括博士。 J.雷维尔、M.布朗、M.韦斯曼、J.戴维斯、T.利奇和J.马利。正在进行的工作将测试几个参与骨形成和调节的候选基因与放射学损伤程度之间的关联。 第二个项目是强直性脊柱炎脊柱融合的进展，是一项开发性研究，旨在通过计算机断层扫描对腰椎间盘钙化进行量化，测试强直性脊柱炎脊柱融合的测量方法。已招募 38 名受试者，其中 33 名受试者已完成 1 年和 2 年的随访扫描。九名受试者已完成测试测量短期可靠性的研究。用于测量韧带骨赘体积和高度的计算机半自动算法已经过优化，以最大限度地提高可靠性。根据这些扫描提供的三维信息，我们发现韧带骨赘非随机分布在椎骨边缘周围，优先形成于后外侧区域。这种定位与高机械应力区域一致，表明生物力学可能是韧带骨赘发育中未被充分认识的因素。我们还开发了这种方法来测量椎体高度和椎间盘高度，这可能有助于精确测量椎体骨折和椎间盘疾病。该项目的合作者是博士。 J. Flynn、L. Yao、Y. Yao 和 S. Tan。 第三个项目“类风湿性关节炎的临床重要变化”是一项针对类风湿性关节炎（RA）活动的临床重要变化的前瞻性观察研究。目前改善 RA 的标准并未强调患者的观点。该项目的目标是根据患者对其症状变化的自我评估，确定 RA 疼痛、功能和整体关节炎状态重要改善的基准。未来的目标是检查偏好测量的测量属性。迄今为止，已入组 262 名患者，并完成了 250 名患者的数据收集。结果表明，患者的改善程度一致，被视为重要的变化，并且已经确定了疼痛、身体功能、患者整体评估和 RA 活动的四项综合指标的改善标准。我们还确定，临床试验反应标准（例如 ACR20）是相当敏感的，但不是具体的改进措施。 第四个项目是身体功能测量，利用临床试验和观察数据的二次分析来了解常用自我报告仪器测量功能的哪些方面。我们发现，绩效衡量指标既不是自我报告功能限制的敏感指标，也不是具体指标。我们还发现，与之前的许多文献相反，女性和男性自我报告的功能限制水平相似。此外，我们发现在调整疾病负担措施后，功能限制没有种族/民族差异，尽管尽管调整了疾病负担，但社会经济地位仍然存在巨大差异。 第五个项目“类风湿性关节炎患者的结果”使用二手数据来检查 RA 患者和非 RA 患者之间的死亡、恶性肿瘤和心血管疾病风险。我们发现类风湿关节炎患者围手术期心血管事件和死亡率的风险并未增加。我们正在计划对类风湿性关节炎患者的结直肠癌和淋巴瘤风险趋势进行研究，该风险趋势可能会随着时间的推移而随治疗方法的变化而变化。 第六个项目是类风湿性关节炎的治疗相关结果，使用原始数据来检查特定的疾病缓解药物是否与高于或低于预期的死亡风险相关，并使用先进的统计方法来解释对病情较重的患者开出更严重药物的差异。我们发现甲氨蝶呤与显着的生存益处相关，而不是归因于引导或选择性药物使用。我们还发现，使用低剂量泼尼松与较高的死亡风险相关，但同时使用缓解疾病的药物（甲氨蝶呤或柳氮磺胺吡啶）会降低这种风险。我们还在研究过去 25 年中社会经济地位较高的患者获得更有效的抗风湿药物的差异是否导致健康方面的社会经济差距随着时间的推移而扩大。 第七个项目“系统性红斑狼疮的临床流行病学”的目标是调查 SLE 患者的健康差异，并确定与健康结果相关的临床特征和医疗保健实践。我们已经完成了对狼疮性肾炎患者终末期肾病风险的系统文献综述，确定了 161 篇报告这些风险的论文。我们现在正在完成对这些数据的贝叶斯荟萃分析，以按治疗时代和世界地理区域估计终末期肾病的风险。 第八个项目“骨科成果”的目标是调查骨科护理过程和结果之间的关联。初步研究使用二手数据，重点关注转子下骨折发生率的时间趋势。在美国，随着时间的推移，发病率的增加与双膦酸盐的使用增加是平行的。此外，非典型髋部骨折的风险与医疗保险受益人对双磷酸盐治疗的依从程度相关。我们进行了一项观察性研究，研究了长期使用双磷酸盐与转子下喙部（转子下骨折的放射学前兆）之间的关联。我们发现转子下喙鸣和长期使用双磷酸盐没有差异，这表明这种骨骼变化并不是治疗的不可避免的结果。我们还研究了与使用钉子或钢板相关的骨折护理结果的差异，并确定围手术期出血是手术部位感染的风险。 第九个项目的目标是测试临床缓解的 RA 患者是否可以安全地退出肿瘤坏死因子-α 抑制剂治疗，而不会出现关节炎复发。我们启动了一项多中心双盲安慰剂对照戒断试验，在 300 名缓解期 RA 患者中检验这一假设。这项研究还将提供有关复发的临床、影像（联合超声和磁共振成像）和免疫学预测因素的数据。