Complications of Immunosupression for Eye Diseases

描述(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，在美国是主要的致盲眼病。对于一些患者来说，皮质类固醇治疗不足以控制 眼部炎症性疾病，需要使用抗代谢药物、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性疾病或其他系统性疾病的患者的研究，有人提出，这种治疗可能会导致癌症和其他疾病风险的增加。在这些研究中，很难确定额外的风险是由潜在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率、癌症和其他重大疾病的过度风险相关。预计这项研究将产生关键信息，以决定是否有必要对此类患者进行免疫抑制治疗，以及是否应该避免某些此类药物。 这项研究将采用经典的回溯性队列设计。接受免疫抑制治疗的患者将被与外部标准、普通联合石板人群进行比较，并与内部对照组进行比较，后者是患有相同眼部炎症性疾病、未接受免疫抑制的患者。据估计，从17-27年前开始，三个中心将积累4695名患者，这些中心率先使用免疫抑制疗法治疗眼病。接受眼科疾病免疫抑制治疗的患者，以及没有接受相同眼部炎症诊断的患者，将通过图表审查来确定。已经死亡的患者将通过搜索国家死亡指数和其他记录系统进行识别。死亡证明将成为特定原因死亡分析的基础。还活着的患者将被联系并询问癌症、骨质疏松症和心脏病的诊断情况。还将询问已死亡的受试者的近亲，以确定此类诊断是否发生在死亡之前。这样的诊断将由一个结果委员会通过病历审查来核实。主要结果--死亡率、特定原因死亡率和癌症/其他疾病发病率--将使用相对发病率方法进行分析。仅根据临床信息分析免疫抑制的有益影响将是次要目标。

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.