日本类风湿关节炎患者的恶性肿瘤发病率及其与生物改善病情抗风湿药的关联：来自IORRA患者登记处的时间依赖性分析
Incidence of Malignancies and the Association with Biological Disease-Modifying Antirheumatic Drugs in Japanese Patients with Rheumatoid Arthritis: A Time-Dependent Analysis from the IORRA Patient Registry.
作者信息
Harigai Masayoshi, Tanaka Eiichi, Inoue Eisuke, Sakai Ryoko, Sugitani Naohiro, Toyoizumi Shigeyuki, Sugiyama Naonobu, Yamanaka Hisashi
机构信息
Department of Rheumatology, Sanno Hospital, 8-10-16 Akasaka, Minato-ku, Tokyo, 107-0052, Japan.
Division of Rheumatology, Department of Internal Medicine, Tokyo Women's Medical University School of Medicine, 8-1 Kawada-Cho, Shinjuku-Ku, Tokyo, 162-8666, Japan.
出版信息
Rheumatol Ther. 2024 Oct;11(5):1181-1195. doi: 10.1007/s40744-024-00689-8. Epub 2024 Jul 17.
INTRODUCTION
Patients with rheumatoid arthritis (RA) may have an increased malignancy risk versus the general population, potentially elevated by biological disease-modifying antirheumatic drug (bDMARD) use. Using patient registry data, we determined malignancy risk, stratified by bDMARD use, among Japanese patients with RA versus the Japanese general population and investigated whether bDMARD use is a time-dependent risk factor for the development of malignancy.
METHODS
Patients aged ≥ 18 years with ≥ 2 data entries of RA in the IORRA (Institute of Rheumatology, Rheumatoid Arthritis) patient registry, enrolled from January 2013-December 2018, were identified ('All RA' cohort). Patients were stratified into bDMARD (≥ 1 bDMARD received) or non-bDMARD (no history of bDMARDs) sub-cohorts. Malignancy incidence rates and standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) versus the Japanese general population were calculated. Risk of RA medication use was analyzed using a time-dependent Cox proportional hazards model, after adjusting for covariates.
RESULTS
A total of 8020 patients were identified for the All RA cohort; 2187 and 5833 for the bDMARD and non-bDMARD sub-cohorts, respectively. For all three cohorts, incidence of overall malignancies was similar versus the Japanese general population. Incidence of specific malignancies was also similar, but incidence of lymphoma was higher for all three cohorts (SIRs [95% CIs] 3.72 [2.71-4.93], 5.97 [3.34-9.59], and 2.79 [1.82-4.02], respectively). In the bDMARD sub-cohort, no increase in SIRs was observed for other site-specific malignancies. In the All RA cohort, use of methotrexate, tacrolimus, glucocorticoids, non-steroidal anti-inflammatory drugs, and bDMARDs were not associated with the risk of overall malignancy; the hazard ratio (95% CI) was 1.36 (0.96-1.93) for bDMARD use. Increased disease activity was a time-dependent risk factor of overall malignancy with a hazard ratio (95% CI) of 1.35 (1.15-1.59).
CONCLUSIONS
The use of bDMARDs was not a time-dependent risk factor for malignancy.
引言
与普通人群相比，类风湿关节炎（RA）患者的恶性肿瘤风险可能增加，生物性改善病情抗风湿药物（bDMARD）的使用可能会进一步提高这一风险。利用患者登记数据，我们确定了日本RA患者与日本普通人群中按bDMARD使用情况分层的恶性肿瘤风险，并调查了bDMARD的使用是否是恶性肿瘤发生的时间依赖性风险因素。
方法
确定2013年1月至2018年12月在IORRA（风湿病学研究所，类风湿关节炎）患者登记处登记的年龄≥18岁且有≥2条RA数据记录的患者（“所有RA”队列）。患者被分为bDMARD（接受过≥1种bDMARD）或非bDMARD（无bDMARD使用史）亚队列。计算与日本普通人群相比的恶性肿瘤发病率和标准化发病率比（SIR）及其95%置信区间（CI）。在调整协变量后，使用时间依赖性Cox比例风险模型分析RA药物使用风险。
结果
“所有RA”队列共确定8020例患者；bDMARD和非bDMARD亚队列分别为2187例和5833例。对于所有三个队列，总体恶性肿瘤的发病率与日本普通人群相似。特定恶性肿瘤的发病率也相似，但所有三个队列的淋巴瘤发病率均较高（SIR[95%CI]分别为3.72[2.71-4.93]、5.97[3.34-9.59]和2.79[1.82-4.02]）。在bDMARD亚队列中，未观察到其他部位特异性恶性肿瘤的SIR增加。在“所有RA”队列中，甲氨蝶呤、他克莫司、糖皮质激素、非甾体抗炎药和bDMARD的使用与总体恶性肿瘤风险无关；bDMARD使用的风险比（95%CI）为1.36（0.96-1.93）。疾病活动度增加是总体恶性肿瘤的时间依赖性风险因素，风险比（95%CI）为1.35（1.15-1.59）。
结论
bDMARD的使用不是恶性肿瘤的时间依赖性风险因素。
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