Psoriasis treatments, cardiovascular disease, and diabetes

描述(申请人提供)：在美国，中到重度牛皮癣影响着150万人。多项精心设计、以人群为基础的观察性研究提供了令人信服的证据，证明牛皮癣与心血管和代谢并发症的风险增加1.5至2倍有关。然而，免疫调节治疗对风险的影响还没有得到充分的评估。也没有对中介生理措施的风险进行评估。我们建议评估中重度银屑病患者使用免疫调节药物改善体重指数、血压、血脂和空腹血糖的比较效果。如果这些生理指标在银屑病中恶化，但对免疫调节治疗有实质性的抵抗力，那么那些高危人群应该被识别出来进行筛查和早期行为干预。另一方面，如果牛皮癣的免疫调节疗法改善或恶化了这些措施，那么医生和患者迫切需要证据来做出合理的治疗决定，在考虑到患者的个人风险概况的情况下，在利益与风险和成本之间进行权衡。正在研究的药物将包括抗肿瘤坏死因子药物、甲氨蝶呤、口服维甲酸和环孢素。这些药物的风险将与没有全身用药的光疗的风险进行比较。符合研究条件的患者数量为8385人，其中有大量患者接触过研究药物(抗肿瘤坏死因子、甲氨蝶呤、口服维甲酸和环孢素A)和对照疗法。由于重点放在生理指标上，这项研究对亚组分析具有很大的影响力，目的是选择患者进行个性化治疗。这项研究将提供可以立即和直接转化为临床环境的信息，以便医生和患者能够在考虑到患者患心血管疾病和糖尿病的潜在风险的情况下做出最佳治疗选择。我们使用保守的假设估计了这项研究的潜在影响。如果优化药物治疗将风险降低5%，那么就可以预防4万例心血管疾病和糖尿病。或者，这项研究可以证明，抗肿瘤坏死因子治疗对心血管疾病和糖尿病的生理风险因素没有好处，在这种情况下，通过保持有效、严格的处方适应症，抗肿瘤坏死因子治疗的价值可以得到优化。这项研究还可以为研究设计和未来对特殊药物的间接益处的评估提供信息。

DESCRIPTION (provided by applicant): Moderate-to-severe psoriasis affects 1.5 million people in the U.S. Multiple, well-designed, population-based observational studies provide convincing evidence that psoriasis is associated with 1.5- to 2-fold increased risk for cardiovascular and metabolic complications. However, the effect of immunomodulatory therapy on risk has not been adequately evaluated. Nor has risk been evaluated with respect to intermediating physiologic measures. We propose to assess the comparative effectiveness of immunomodulatory drugs used by patients with moderate-to-severe psoriasis for improving body mass index, blood pressure, lipids, and fasting plasma glucose. If these physiologic measures are worsened in psoriasis but are substantially resistant to immunomodulatory therapy, then those at high risk should be identified for screening and early behavioral intervention. On the other hand, if immunomodulatory therapy for psoriasis improves or worsens these measures, then evidence is urgently needed by doctors and patients to make sound treatment decisions that balance benefits against risks and costs given the patient's personal risk profile. The drugs under study will include anti-TNF agents, methotrexate, oral retinoids and cyclosporine. Risk on these drugs will be compared to risk on phototherapy without systemic agent. The number of patients eligible for the study is 8385, with ample numbers having exposure to the study drugs (anti-TNF, methotrexate, oral retinoids, and cyclosporine) and comparison therapy. Because the focus is on physiologic measures, the study has substantial power for subgroup analysis, with the goal of selecting patients for personalized therapy. The study will provide information that can be translated immediately and directly to the clinical setting so that doctors and patients can make the best treatment choices given the patient's underlying risk for cardiovascular disease and diabetes. We have estimated the potential impact of the study using conservative assumptions. If optimizing drug therapy reduces risk by even 5%, then 40,000 cases of cardiovascular disease and diabetes could be prevented. Alternatively, the study could demonstrate no benefit of anti-TNF therapy on physiologic risk factors for cardiovascular disease and diabetes, in which case the value of anti-TNF therapy could be optimized by maintaining valid, tight prescribing indications. The study could also inform study design and future assessments of the indirect benefits of specialty pharmaceuticals.