Complications of Immunosupression for Eye Diseases

描述（由申请人提供）：眼部炎症性疾病，包括葡萄膜炎、巩膜炎和粘膜类天疱疮，是美国主要的致盲性眼病。 对于某些患者，皮质类固醇治疗不足以控制 眼部炎性疾病，需要用抗代谢药、T细胞抑制剂和/或烷化剂治疗进行免疫抑制。 根据对患有严重免疫或其他全身性疾病的患者的研究，已经表明这种治疗可能导致癌症和其他疾病的风险增加。 在这些研究中，很难确定超额风险是由基础疾病还是治疗引起的。 我们建议直接评估眼部炎症性疾病的免疫抑制治疗是否与死亡、癌症和其他主要疾病的过度风险相关。这项研究有望为决定这些患者是否需要免疫抑制治疗以及是否应该避免某些此类药物提供关键信息。 本研究将采用经典的回顾性队列设计。 将“暴露于”免疫抑制治疗的患者与外部标准（一般美国人群）和内部对照组（未接受免疫抑制治疗的相同眼部炎症性疾病患者）进行比较。 据估计，17-27年前开始使用免疫抑制疗法治疗眼病的三个中心将增加4,695名患者。 将通过病历审查确定接受免疫抑制治疗的眼部疾病患者和未接受免疫抑制治疗的相同眼部炎症诊断的患者。 死亡的患者将通过国家死亡指数和其他记录系统的搜索来确定。 死亡证明将是具体死因死亡率分析的基础。 将联系仍存活的患者，并询问其癌症、心脏病和心脏病诊断的发生情况。 还将询问死亡受试者的近亲，以确定这些诊断是否发生在死亡前。这些诊断将通过结果委员会的病历审查进行验证。主要结局-死亡率、病因特异性死亡率和癌症/其他疾病发生率-将使用相对发生率方法进行分析。 仅基于临床信息分析免疫抑制的有益作用将是次要目的。

DESCRIPTION (provided by applicant): Ocular inflammatory diseases, including uveitis, scleritis, and mucous membrane pemphigoid, are major blinding eye diseases in the United States. For some patients, corticosteroid therapy is insufficient to control ocular inflammatory disease, requiring immunosuppression with antimetabolite, T-cell inhibitor, and/or alkylating agent therapies. It has been suggested, based on studies of patients with severe immunologic or other systemic diseases, that such treatments may result in an increased risk of cancer and other morbidities. In these studies, it has been difficult to determine whether the excess risk arose from the underlying diseases or the treatment. We propose to evaluate directly whether immunosuppressive therapy for ocular inflammatory diseases is associated with an excess risk of mortality, cancer, and other major diseases. The study is expected to generate critical information in deciding whether immunosuppressive therapy is warranted for such patients, and whether certain such agents should be avoided. The study will have a classic retrospective cohort design. Patients "exposed" to immunosuppressive therapies will be compared to an external standard, the general United Slates population, and to an internal comparison group, patients with the same ocular inflammatory diseases who did not receive immunosuppression. An estimated 4,695 patients will be accrued from three centers which pioneered the use of immunosuppressive therapy for eye diseases, beginning 17-27 years ago. Patients who received immunosuppressive therapy for eye diseases, and patients with the same ocular inflammatory diagnoses who did not, will be identified by chart reviews. Patients who have died will be identified through search of the National Death Index and other record systems. Death certificates will be the basis for cause-specific mortality analyses. Patients still living will be contacted and queried regarding the occurrence of cancer, osteoporotic, and heart disease diagnoses. Next of kin will also be queried for subjects who have died to ascertain whether such diagnoses occurred prior to death. Such diagnoses will be verified by medical record review by an outcomes committee. The primary outcomes-mortality, cause-specific mortality, and cancer/other disease incidence-will be analyzed using a relative incidence approach. Analysis of the beneficial effects of immunosuppression, based on clinical information only, will be a secondary objective.