Comparative Effectiveness of Biologics for Psoriasis

描述(由申请人提供)： Gelfand，Joel M研究领域：(05)比较有效性研究，05-AR-101生物制品在自身免疫性风湿病和皮肤病中的比较有效性应用标题：生物制品对牛皮癣的比较有效性牛皮癣是一种由Th-1、Th-17介导的慢性炎症性疾病，影响着700多万美国人。银屑病，尤其是严重的银屑病，与身体和情感健康功能的严重残疾有关，最近被证明是心血管疾病的独立危险因素，并与过高的全因死亡率有关。最近牛皮癣的治疗经历了一场革命，FDA在过去7年中批准了至少5种生物疗法，对导致牛皮癣的遗传学和免疫/炎症途径的了解取得了进展，以及针对全新途径的研究性生物制剂的开发。虽然这些新疗法在短期研究中已被证明对牛皮癣有效，但它们与过高的成本、严重副作用的风险仍在确定以及长期治疗的有效性降低有关。牛皮癣研究中的这些巨大进步并没有反映在指导个别患者治疗决定的研究中。因此，为了对中、重度银屑病患者做出信息丰富的治疗决策并提高护理质量，迫切需要在这一领域进行比较有效性研究。为了响应挑战奖05-AR-101，我们提议建立一个高度创新的公私合作伙伴关系，称为CERSDN(发音为“SIRS-DEN”)，这是皮肤病网络比较有效性研究的首字母缩写，以严格研究生物制剂对牛皮癣的比较有效性。根据美国复苏和再投资法案，CERSDN将在生物医学研究领域创造至少3个新的就业机会，以刺激费城、圣路易斯和盐湖城三个不同的地方经济。我们将从来自学术实践、私人实践和来自全美各地的国家牛皮癣基金会患者成员的大量且多样化的牛皮癣患者群体中获取数据。这一目标将解决在牛皮癣中进行比较有效性研究的一个主要障碍，因为此类研究只能通过多学科合作小组进行，而皮肤病领域的这种基础设施在美国不存在。通过CERSDN，我们将对皮肤科医生和患者进行调查，以确定在为患者护理提供信息所必需的比较有效性研究中应优先考虑的关键因素，并将确定牛皮癣患者参与未来评估中、重度牛皮癣治疗方法的比较有效性的意愿。这一目标将为规划未来的、纵向的、使用黄金标准设计的比较有效性研究提供必要的数据，例如大型简单试验。最后，我们将在大量不同的患者群体中进行一系列横断面研究，以评估现有治疗中重度牛皮癣的比较有效率，如光疗、阿维A、甲氨蝶呤、环孢素A、阿法塞普、依那西普、阿达利米单抗、英夫利昔单抗和乌司替尼单抗。这一目标将决定这些疗法目前在患者(例如与健康相关的生活质量、经济影响和治疗满意度)和医生报告的结果(如牛皮癣影响的身体表面积)方面在特定时间点的不同亚组患者中的表现。最终，通过史无前例的挑战机会赠款05-AR-101，我们将进行研究，以创造就业机会，刺激经济，并解决优化牛皮癣患者护理所需的基本知识差距。这项建议将为牛皮癣患者的治疗决定和未来的纵向比较有效性研究提供必要的信息。最终，这一系列研究将导致更合理的治疗决定，并改善700万患有牛皮癣的美国人的患者护理。

DESCRIPTION (provided by applicant): Gelfand, Joel M Research Area: (05) Comparative Effectiveness Research, 05-AR-101 Comparative Effectiveness (CE) of Biologics in Autoimmune Rheumatic and Skin Diseases Title of application: Comparative Effectiveness of Biologics for Psoriasis Psoriasis is a chronic, inflammatory Th-1, Th-17 mediated disease that affects over 7 million Americans. Psoriasis, particularly when severe, is associated with serious disability in physical and emotional health function, has been recently demonstrated to be an independent risk factor for cardiovascular disease, and is associated with excess all-cause mortality. The treatment of psoriasis has recently undergone a revolution, with the FDA approval of at least 5 biologic therapies in the last 7 years, advances in understanding of the genetics and the immune/inflammatory pathways that drive psoriasis, as well as the development of investigational biologics that target completely novel pathways. Although these new therapies have been proven efficacious for psoriasis in short term studies, they are associated with excessive costs, risks of serious side effects that are still being defined, and diminished efficacy with long term treatment. These large strides in psoriasis research have not been mirrored in research that would guide treatment decisions for individual patients. Thus, to make informative treatment decisions and improve the quality of care of moderate to severe psoriasis patients, it is urgent that comparative effectiveness studies be conducted in this area. In response to Challenge grant 05-AR-101, we propose the creation of a highly innovative public-private partnership called CERSDN (pronounced "Sirs-DEN"), the acronym for the Comparative Effectiveness Research in Skin Disease Network, to rigorously study the comparative effectiveness of biologics for psoriasis. Consistent with the American Recovery and Reinvestment Act, CERSDN will create a minimum of 3 new jobs in biomedical research stimulating three different local economies in Philadelphia, St. Louis, and Salt Lake City. We will capture data from a large and diverse population of psoriasis patients from academic practice, private practice, and patient members of the National Psoriasis Foundation from across the United States. This aim will address a major barrier to the conduct of comparative effectiveness studies in psoriasis as such studies can only be conducted through multi-disciplinary collaborative groups, and such an infrastructure in the dermatology field does not exist in United States. Through CERSDN we will conduct surveys of dermatologists and patients in order to determine the key elements that should be prioritized in comparative effectiveness research necessary to inform patient care and will determine the willingness of psoriasis patients to participate in future longitudinal studies evaluating the comparative effectiveness of therapies for moderate to severe psoriasis. This aim will provide essential data for planning future, longitudinal, comparative effectiveness studies using gold standard designs such as large simple trials. Finally, we will perform a series of cross-sectional studies in a large and diverse patient population to evaluate the period prevalence of comparative effectiveness of existing therapies for moderate to severe psoriasis such as phototherapy, acitretin, methotrexate, cyclosporine, alefacept, etanercept, adalimumab, infliximab, and ustekinumab. This aim will determine how these therapies currently perform with respect to patient (e.g. health related quality of life, economic impact, and treatment satisfaction) and physician reported outcomes (such as body surface area affected by psoriasis) in various subgroups of patients treated in routine clinical practice at a given point in time. Ultimately, through the unprecedented opportunity of Challenge grant 05-AR-101 we will conduct research that will create jobs, stimulate the economy, and address essential knowledge gaps required to optimize care of patients with psoriasis. This proposal will provide information essential to informing treatment decisions for patients with psoriasis and future, longitudinal comparative effectiveness studies. Ultimately, this line of research will lead to more rationale treatment decisions and improved patient care for the > 7 million Americans who suffer from psoriasis.