Pharmacy Outcomes Research Group, Kaiser Permanente Medical Care Program, Oakland, CA, USA.
Ann Pharmacother. 2009 Dec;43(12):1956-63. doi: 10.1345/aph.1M278. Epub 2009 Nov 10.
The Food and Drug Administration has issued a public health advisory regarding cancer risk from topical calcineurin inhibitors.
To compare the rates of cancer among patients with common dermatologic conditions who were exposed or not exposed to topical calcineurin inhibitors.
A retrospective cohort observational study used data from an integrated healthcare delivery system on 953,064 subjects with diagnoses of atopic dermatitis or eczema between 2001 and December 2004. The main endpoint was initial cancer diagnosis. Chart review was performed to confirm cancer diagnosis in the subjects exposed to topical calcineurin inhibitors when any particular cancer rate was at least 3 times higher than that in unexposed subjects. Data were analyzed using the Cox proportional hazards model.
Age- and sex-adjusted hazard ratios for all cancers were 0.93 (95% CI 0.81 to 1.07; p = 0.306) for tacrolimus-exposed versus -unexposed subjects and 1.15 (95% CI 0.99 to 1.31; p = 0.054) for pimecrolimus-exposed versus -unexposed subjects. T-cell lymphoma was the only cancer associated with a significantly increased risk among subjects exposed to tacrolimus (HR = 5.04, 95% CI 2.39 to 10.63; p < 0.001) or pimecrolimus (HR = 3.76, 95% CI 1.71 to 8.28; p = 0.010). Subsequent chart review of subjects in the exposed group with T-cell lymphoma found that 4 of 16 had skin lesions that were suspected to be the early lesions of T-cell lymphoma prior to exposure to tacrolimus or pimecrolimus. After these 4 cases were excluded, the age and sex hazard ratio for T-cell lymphoma was 5.44 (95% CI 2.51 to 11.79; p < 0.001) for tacrolimus and 2.32 (95% CI 0.89 to 6.07; p = 0.086) for pimecrolimus. There was no statistically significantly increased risk for other subgroups of cancer, including melanoma.
Exposure to topical tacrolimus or pimecrolimus was not associated with an increase in the overall cancer rate. Use of topical tacrolimus may be associated with an increased risk of T-cell lymphoma.
美国食品药品监督管理局发布了一项关于局部钙调神经磷酸酶抑制剂致癌风险的公共卫生咨询。
比较患有常见皮肤病的患者在接触或不接触局部钙调神经磷酸酶抑制剂时的癌症发病率。
一项回顾性队列观察性研究使用了 2001 年至 2004 年 12 月期间来自综合医疗服务系统的 953064 名特应性皮炎或湿疹患者的数据。主要终点是首次癌症诊断。当任何特定癌症发病率至少是未暴露组的 3 倍时，对暴露于局部钙调神经磷酸酶抑制剂的患者进行病历回顾以确认癌症诊断。使用 Cox 比例风险模型进行数据分析。
年龄和性别调整后的所有癌症风险比（HR）分别为他克莫司暴露组与未暴露组（0.93；95%置信区间[CI]0.81 至 1.07；p = 0.306）和吡美莫司暴露组与未暴露组（1.15；95%CI0.99 至 1.31；p = 0.054）。T 细胞淋巴瘤是唯一与他克莫司暴露组（HR = 5.04，95%CI2.39 至 10.63；p <0.001）或吡美莫司暴露组（HR = 3.76，95%CI1.71 至 8.28；p = 0.010）相关的癌症风险显著增加。对暴露组中患有 T 细胞淋巴瘤的患者进行后续病历回顾发现，在暴露于他克莫司或吡美莫司之前，有 4 例患者的皮肤病变被怀疑是 T 细胞淋巴瘤的早期病变。排除这 4 例后，他克莫司和吡美莫司的 T 细胞淋巴瘤年龄和性别风险比分别为 5.44（95%CI2.51 至 11.79；p <0.001）和 2.32（95%CI0.89 至 6.07；p = 0.086）。其他癌症亚组，包括黑色素瘤，风险没有统计学意义的增加。
局部使用他克莫司或吡美莫司与总体癌症发生率增加无关。局部使用他克莫司可能与 T 细胞淋巴瘤风险增加有关。
