Diagnostic and treatment landscape of pyoderma gangrenosum

坏疽性脓皮病的诊治现状

• 批准号: 10732688
• 负责人: Alex Ortega Loayza
• 金额: $ 25.7万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-02 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10732688
• 关键词: Address; Adopted; Adoption; Adrenal Cortex Hormones; Adult; Affect; Agreement; Alternative Therapies; Antibiotics; Biological Products; Chronic; Clinical; Clinical Research; Clinical Trials; Collaborations; Comparison arm; Consensus; Country; Cyclosporine; Data; Development; Diagnosis; Diagnostic; Disease; Enrollment; Ensure; Expert Opinion; FDA approved; Future; Goals; Guidelines; Health; Health Care Costs; Healthcare; Heart Diseases; Immunosuppression; Immunosuppressive Agents; Inflammatory; Inpatients; Institution; International; Intravenous; Knowledge; Lead; Medical; Operative Surgical Procedures; Oregon; Outcome; Pain; Pain management; Patients; Performance; Pharmaceutical Preparations; Practice Management; Process; Prospective Studies; Protocols documentation; Psychological Impact; Pyoderma Gangrenosum; Quality of life; Reporting; Research; Research Design; Research Personnel; Retrospective Studies; Safety; Science; Scientist; Signal Transduction; Skin; Standardization; TNF gene; Therapeutic; Treatment outcome; United States; Universities; Variant; accurate diagnosis; care burden; chronic infection; chronic ulcer; clinical care; clinical practice; cohort; design; diagnostic strategy; effectiveness evaluation; evidence based guidelines; future implementation; healing; improved; inclusion criteria; inhibitor; innovation; limb amputation; middle age; molecular diagnostics; mortality; mortality risk; novel therapeutics; prospective; skin ulcer; standard of care; success; treatment comparison; unnecessary treatment; wound; wound care

Pyoderma gangrenosum (PG) is a rare, chronic, inflammatory disorder that presents with painful skin ulcers. It causes disfiguration, negatively impacts quality of life, and increases mortality. Despite being a disease with significant physical and psychological impact, it remains understudied. The paucity of clinical research in the field is likely due to challenges in diagnosis and unknown treatment outcomes. Misdiagnosis, which is reported in up to 39% of patients, has been one of the main obstacles to proper implementation and enrollment in clinical trials. Because molecular diagnostics remain years away, researchers rely on clinical criteria for diagnosis. Three diagnostic frameworks exist based on clinical findings, however they are not widely applied or accepted. Moreover, the mainstay of treatment for PG is immunosuppression. Monotherapy with systemic corticosteroids or cyclosporine is the classical initial treatment, and only a few clinical trials have evaluated the effectiveness and safety of new therapeutic alternatives such as biologics. Further, combination or concomitant therapy of classic immunosuppression and biologics has been adopted as a new standard of care without high-quality data. Current therapeutic approaches are based on expert opinion guidelines creating additional difficulty in implementing clinical trials and hampering the FDA approval process of potential drugs. Our proposal aligns with the overall long-term goals of our research group: to drive diagnostic and therapeutic innovation in the field of PG – a significantly understudied disease with an increased healthcare burden. Our short-term goals include: 1) to establish which diagnostic framework best performs in a multi-institutional collaborative study, supporting its applicability in medical practice and clinical trials, and 2) to analyze current treatment outcomes in clinical practice. We seek to accomplish our short-term goals utilizing the following specific aims: Aim 1) compare and assess the three diagnostic frameworks in a multi-center prospective study of a well- defined cohort of patients diagnosed with PG and PG-like conditions to determine their performance in diagnosis, and Aim 2) determine the effectiveness of real-world therapeutic approaches currently used as standard of care in a multi-center cohort of patients with PG. Our established PG research team at OHSU has the ability to implement a multi-institutional collaborative effort to ensure the success of this proposal. Collectively, the results of this project will fill the diagnostic and therapeutic gaps in knowledge and define the current landscape of PG in the United States.

脓性坏疽（PG）是一种罕见的慢性炎症性疾病，表现出疼痛的皮肤溃疡。 导致毁容，对生活质量产生负面影响并增加死亡率。尽管是一种疾病 巨大的身体和心理影响，它仍然被理解。在 领域可能是由于诊断和未知治疗结果的挑战所致。误诊，据报道 在多达39％的患者中，已成为适当实施和入学临床的主要障碍之一 试验。由于分子诊断仍在数年中，研究人员依靠临床标准进行诊断。三 根据临床发现存在诊断框架，但是并未被广泛应用或接受。 此外，PG治疗的支柱是免疫抑制。全身性皮质类固醇单一疗法 或环孢菌素是经典的初始治疗，只有少数临床试验评估了有效性 和新治疗替代品（例如生物制剂）的安全。此外，结合或伴随的治疗 经典的免疫抑制和生物制剂已被用作新的护理标准，而没有高质量数据。 当前的治疗方法基于专家意见准则，在 实施临床试验并妨碍FDA批准过程。 我们的建议与研究小组的整体长期目标保持一致：推动诊断和治疗 PG领域的创新 - 这是一种显着理解的疾病，医疗保健负担增加。我们的 短期目标包括：1）确定在多机构中最能表现哪种诊断框架 协作研究，支持其在医学实践和临床试验中的适用性，以及2）分析当前 临床实践中的治疗结果。我们试图利用以下特定的特定来实现我们的短期目标 目的：目标1）在一项良好的多中心前瞻性研究中比较和评估三个诊断框架 确定患有PG和PG样疾病的患者的定义队列，以确定其在诊断方面的表现， 目标2）确定当前用作护理标准的现实世界治疗方法的有效性 在多中心的PG患者中。 我们在OHSU建立的PG研究团队有能力实施多机构的合作努力 确保该提案的成功。总的来说，该项目的结果将填充诊断和治疗性 Knowle的差距并定义了美国当前的PG景观。