Buchanich Jeanine M, Newcomb Craig W, Washington Terri L, Foster Charles Stephen, Sobrin Lucia, Thorne Jennifer E, Jabs Douglas Alan, Suhler Eric B, Rosenbaum James T, Sen Hatice Nida, Levy-Clarke Grace A, Nussenblatt Robert B, Bhatt Nirali P, Lowder Careen Y, Goldstein Debra A, Leiderman Yannek I, Acharya Nisha R, Holland Gary N, Read Russell W, Dunn James P, Dreger Kurt A, Artornsombudh Pichaporn, Begum Hosne A, Fitzgerald Tonetta D, Kothari Srishti, Payal Abhishek R, Daniel Ebenezer, Gangaputra Sapna S, Kaçmaz Roje Oktay, Liesegang Teresa L, Pujari Siddharth S, Khachatryan Naira, Maghsoudlou Armin, Suga Hilkiah K, Pak Clara M, Helzlsouer Kathy J, Kempen John H
Department of Biostatistics, University of Pittsburgh School of Public Health, Pittsburgh, Pennsylvania, USA.
Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
BMJ Oncol. 2023 Aug 21;2(1):e000037. doi: 10.1136/bmjonc-2023-000037. eCollection 2023.
Evaluate the association between cancer incidence and immunosuppressive treatment in patients with ocular inflammatory disease (OID).
We performed a retrospective cohort study of patients from 10 US OID subspecialty practices. Patients with non-infectious OID were included; HIV-infected patients were excluded. Time-dependent exposure to drug classes (ie, antimetabolites, calcineurin inhibitors, alkylating agents, tumour necrosis factor (TNF) inhibitors) and drugs were evaluated. Cancer incidence was ascertained by linkage to 12 state cancer registries from 1996 to 2015. Cancer incidence was analysed using Cox regression survival analysis, using 0-year, 3-year and 5-year lags after immunosuppression began.
The cancer incidence cohort comprised 10 872 individuals at risk of incident cancer and residing in one of the 12 states covered; 812 primary cancers were identified through cancer incidence tracing with median follow-up time of 10 years. Neither TNF inhibitor, antimetabolite, calcineurin inhibitor nor alkylating agent classes were associated with statistically significant increases in cancer incidence adjusting for covariates. We found statistically significant reduced hazards in the systemic inflammatory disease (SID)-including cohort for adalimumab and chlorambucil, increased hazards for tacrolimus and etanercept in the non-SID cohort and reduced hazards for methotrexate in both. Other immunosuppressive drugs were not associated with overall cancer incidence.
We found no increased risk of overall or site-specific cancer incidence associated with short-term (non-transplant) therapy with most commonly used immunosuppressive drug classes and many specific drugs. Further research may clarify potentially protective or harmful effects of specific agents that were not consistently associated with reduced or increased cancer incidence.
NCT00116090.
评估眼部炎性疾病（OID）患者癌症发病率与免疫抑制治疗之间的关联。
我们对来自美国10个OID亚专业诊所的患者进行了一项回顾性队列研究。纳入非感染性OID患者；排除HIV感染患者。评估了药物类别（即抗代谢药、钙调神经磷酸酶抑制剂、烷化剂、肿瘤坏死因子（TNF）抑制剂）和药物的时间依赖性暴露情况。通过与1996年至2015年12个州的癌症登记处建立联系来确定癌症发病率。使用Cox回归生存分析对癌症发病率进行分析，采用免疫抑制开始后的0年、3年和5年滞后时间。
癌症发病率队列包括10872名有患癌风险且居住在12个覆盖州之一的个体；通过癌症发病率追踪确定了812例原发性癌症，中位随访时间为10年。在调整协变量后，TNF抑制剂、抗代谢药、钙调神经磷酸酶抑制剂或烷化剂类别均与癌症发病率的统计学显著增加无关。我们发现，在全身性炎性疾病（SID）患者队列中，阿达木单抗和苯丁酸氮芥的风险显著降低；在非SID患者队列中，他克莫司和依那西普的风险增加；在两个队列中，甲氨蝶呤的风险均降低。其他免疫抑制药物与总体癌症发病率无关。
我们发现，大多数常用免疫抑制药物类别和许多特定药物的短期（非移植）治疗与总体或特定部位癌症发病率的增加风险无关。进一步的研究可能会阐明与癌症发病率降低或增加无一致关联的特定药物的潜在保护或有害作用。
NCT00116090。
