University of Southern Denmark, Odense C, Denmark.
RTI Health Solutions, Barcelona, Spain.
Basic Clin Pharmacol Toxicol. 2018 Jun;122(6):612-619. doi: 10.1111/bcpt.12965. Epub 2018 Feb 22.
The purpose of this study was to estimate the incidence rate (IR) of 10 common cancers in new users of antimuscarinic overactive bladder (OAB) medications. We conducted a cohort study using data recorded in Danish registers for patients newly exposed to the OAB drugs, darifenacin, fesoterodine, oxybutynin, solifenacin, tolterodine or trospium in years 2004-2012, aged ≥18 years and without cancer before treatment initiation. We estimated IRs for each study cancer (bladder, breast, colorectal, lung, melanoma, non-Hodgkin lymphoma, pancreas, prostate, renal and uterine), standardised by age and sex and explored IR trends over time since treatment initiation. For all cancer analyses, only the first incident targeted cancer was considered. Of 72,917 patients (60% women; mean age at treatment start: 66 years), 3475 developed a study cancer during 259,072 person-years of follow-up. The most common study cancers were prostate (48.1% of study cancers in men), breast (40.0% of study cancers in women) and lung (15.4% of all study cancers). The overall standardised study cancer IR was 5.4 per 1000 person-years (95% confidence interval, 5.3-5.6); IRs were similar across individual OAB drugs. The standardised IRs for bladder and prostate cancers, which have symptoms in common with OAB, were highest in the first 6 months of treatment initiation and lower thereafter. In contrast, IRs for other study cancers were nearly constant during follow-up. Cancer IRs did not vary substantially by individual OAB drug. Protopathic bias is a plausible explanation for the higher rates of bladder and prostate cancers observed soon after starting OAB drug treatment.
本研究旨在估计新使用抗毒蕈碱性膀胱过度活动症（OAB）药物的患者中 10 种常见癌症的发病率（IR）。我们使用丹麦登记处记录的 2004-2012 年期间新暴露于 OAB 药物（达非那新、非索罗定、奥昔布宁、索利那新、托特罗定或托特罗定）的患者的数据，进行了一项队列研究，年龄≥18 岁，治疗开始前无癌症。我们根据年龄和性别对每个研究癌症（膀胱癌、乳腺癌、结直肠癌、肺癌、黑色素瘤、非霍奇金淋巴瘤、胰腺癌、前列腺癌、肾癌和子宫癌）的 IR 进行了估计，并探讨了治疗开始后随时间的 IR 趋势。对于所有癌症分析，仅考虑了首次发生的目标癌症。在 72917 名患者（60%为女性；治疗开始时的平均年龄：66 岁）中，有 3475 名患者在 259072 人年的随访期间发生了研究癌症。最常见的研究癌症是前列腺癌（男性研究癌症的 48.1%）、乳腺癌（女性研究癌症的 40.0%）和肺癌（所有研究癌症的 15.4%）。总的标准化研究癌症发病率为 5.4/1000 人年（95%置信区间：5.3-5.6）；不同 OAB 药物的发病率相似。与 OAB 具有共同症状的膀胱癌和前列腺癌的标准化发病率在治疗开始的前 6 个月最高，此后较低。相比之下，其他研究癌症的发病率在随访期间几乎保持不变。癌症发病率与个别 OAB 药物没有显著差异。原型偏倚是治疗开始后不久观察到膀胱癌和前列腺癌发生率较高的一个合理解释。
