Confavreux C, Saddier P, Grimaud J, Moreau T, Adeleine P, Aimard G
Service de Neurologie, Hôpital de I'Antiquaille, Lyon, France.
Neurology. 1996 Jun;46(6):1607-12. doi: 10.1212/wnl.46.6.1607.
An increased risk of cancer has been reported in patients treated with azathioprine. To assess the long-term risk of neoplasia in azathioprine-treated multiple sclerosis (MS) patients, we conducted a case-control study using the Lyon Multiple Sclerosis Database. From the 1,191 MS patients included in the database, we identified patients who developed cancer before December 31, 1991. Each case was then matched to three cancer-free MS controls by gender, date of birth, and date of MS onset. A matched analysis was performed to compare cases and controls for exposure to azathioprine therapy during the same follow-up period. Twenty-three MS patients with cancer were identified: 17 solid tumors, 2 skin carcinomas, 4 hematopoietic cancers. Cases had a mean age of 34.5 years +/- 10.2 (+/- SD) at clinical onset of MS and have been followed up for an average 13.8 years +/- 8.1 before being diagnosed with cancer. Fourteen cases (61%) and 34 controls (49%) had been treated with azathioprine for at least 1 month after being diagnosed with MS (adjusted odds ratio = 1.7; 95% confidence interval [CI], 0.6 to 4.6). When assessing risk associated with different durations of azathioprine therapy compared with no treatment at all, we found that MS patients had an increase in cancer risk of 1.3 (95% CI, 0.4 to 4.0) when treated less than 5 years, of 2.0 (95% CI, 0.4 to 9.1) when treated 5 to 10 years, and of 4.4 (95% CI 0.9 to 20.9) when treated more than 10 years. Similar results were obtained when assessing cancer risk associated with cumulative doses of azathioprine ever taken. This case-control study suggests that the overall long-term risk of cancer from azathioprine is low in MS patients. The results are suggestive of a dose-response relationship with no significant risk during the first years of treatment and a possible increased risk after about 10 years of continuous therapy. Further studies are needed to better assess the risk-benefit ratio of azathioprine in MS.
已有报告称，接受硫唑嘌呤治疗的患者患癌风险增加。为评估硫唑嘌呤治疗的多发性硬化症（MS）患者发生肿瘤的长期风险，我们利用里昂多发性硬化症数据库进行了一项病例对照研究。在数据库纳入的1191例MS患者中，我们确定了在1991年12月31日前患癌的患者。然后根据性别、出生日期和MS发病日期，为每例患者匹配3名无癌的MS对照。进行匹配分析以比较病例和对照在同一随访期内接受硫唑嘌呤治疗的情况。确定了23例患癌的MS患者：17例实体瘤、2例皮肤癌、4例造血系统癌症。病例在MS临床发病时的平均年龄为34.5岁±10.2（±标准差），在被诊断为癌症前平均随访了13.8年±8.1年。14例病例（61%）和34例对照（49%）在被诊断为MS后接受了至少1个月的硫唑嘌呤治疗（校正比值比=1.7；95%置信区间[CI]，0.6至4.6）。在评估与不同疗程硫唑嘌呤治疗相关的风险（与未治疗相比）时，我们发现，治疗时间不足5年的MS患者患癌风险增加1.3倍（95%CI，0.4至4.0），治疗5至10年的患者增加2.0倍（95%CI，0.4至9.1），治疗超过10年的患者增加4.4倍（95%CI，0.9至20.9）。在评估与曾服用的硫唑嘌呤累积剂量相关的患癌风险时，也获得了类似结果。这项病例对照研究表明，MS患者因硫唑嘌呤导致的总体长期患癌风险较低。结果提示存在剂量反应关系，在治疗的最初几年无显著风险，而在持续治疗约10年后可能风险增加。需要进一步研究以更好地评估硫唑嘌呤在MS中的风险效益比。
