Staples Margaret P, March Lyn, Hill Catherine, Lassere Marissa, Buchbinder Rachelle
1Monash Department of Clinical Epidemiology, Cabrini Institute, Melbourne, Australia.
2Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.
BMC Rheumatol. 2019 Jan 8;3:1. doi: 10.1186/s41927-018-0050-7. eCollection 2019.
Tumour necrosis factor inhibitor (TNFi) therapy has been available for rheumatoid arthritis (RA) patients for several decades but data on the long-term risk of malignancy associated with its use is limited. Our aims were to assess malignancy risk in a cohort of Australian RA patients relative to the Australian population and to compare cancer risk for patients exposed to TNFi therapy versus a biologic-naïve group.
Demographic data for RA participants enrolled in the Australian Rheumatology Association Database (ARAD) before 31 Dec 2012 were matched to national cancer records in May 2016 (linkage complete to 2012). Standardised incidence ratios (SIRs) were used to compare malignancy incidence in TNFi-exposed and biologic-naïve ARAD participants with the Australian general population using site-, age- and sex-specific rates by calendar year. Malignancy incidence in TNFi-exposed participants and biologic-naïve RA patients, were compared using rate ratios (RRs), adjusted for age, sex, smoking, methotrexate use and prior malignancy.
There were 107 malignancies reported after 10,120 person-years in the TNFi-exposed group ( = 2451) and 49 malignancies after 2232 person-years in the biologic-naïve group ( = 574). Compared with the general population, biologic-naïve RA patients showed an increased risk for overall malignancy (SIR 1.52 (95% confidence interval (CI) 1.16, 2.02) prostate cancer (SIR 2.10, 95% CI 1.18, 4.12). The risk of lung cancer was increased for both biologic naïve and TNFi-exposed patients compared with the general population (SIR 2.69 (95% CI 1.43 to 5.68) and SIR 1.69 (95% CI 1.05 to 2.90) respectively). For the TNFi-exposed patients there was an increased risk of lymphoid cancers (SIR 1.82, 95% CI 1.12, 3.18). There were no differences between the exposure groups in the risk of cancer for any of the specific sites examined.
Overall malignancy incidence was elevated for biologic-naïve RA patients but not for those exposed to TNFi. TNFi exposure did not increase malignancy risk beyond that experienced by biologic-naïve patients. Lung cancer risk was increased for both TNFi-treated and biologic-naïve RA patients compared with the general population suggesting that RA status or RA treatments other than TNFi may be responsible in some way.
肿瘤坏死因子抑制剂（TNFi）疗法已应用于类风湿关节炎（RA）患者数十年，但关于其使用相关的长期恶性肿瘤风险的数据有限。我们的目的是评估一组澳大利亚RA患者相对于澳大利亚人群的恶性肿瘤风险，并比较接受TNFi治疗的患者与未使用生物制剂的患者的癌症风险。
将2012年12月31日前纳入澳大利亚风湿病协会数据库（ARAD）的RA参与者的人口统计学数据与2016年5月的国家癌症记录进行匹配（关联至2012年完整）。使用标准化发病率比（SIRs），按日历年份、部位、年龄和性别特异性率，比较接受TNFi治疗和未使用生物制剂的ARAD参与者与澳大利亚普通人群的恶性肿瘤发病率。使用发病率比（RRs）比较接受TNFi治疗的参与者和未使用生物制剂的RA患者的恶性肿瘤发病率，并对年龄、性别、吸烟、甲氨蝶呤使用情况和既往恶性肿瘤进行调整。
接受TNFi治疗的组在10120人年中有107例恶性肿瘤报告（n = 2451），未使用生物制剂的组在2232人年中有49例恶性肿瘤报告（n = 574）。与普通人群相比，未使用生物制剂的RA患者总体恶性肿瘤风险增加（SIR 1.52（95%置信区间（CI）1.16，2.02），前列腺癌（SIR 2.10，95% CI 1.18，4.12）。与普通人群相比，未使用生物制剂和接受TNFi治疗的患者肺癌风险均增加（分别为SIR 2.69（95% CI 1.43至5.68）和SIR 1.69（95% CI 1.05至2.90））。对于接受TNFi治疗的患者，淋巴癌风险增加（SIR 1.82，95% CI 1.12，3.18）。在任何检查的特定部位的癌症风险方面，暴露组之间没有差异。
未使用生物制剂的RA患者总体恶性肿瘤发病率升高，但接受TNFi治疗的患者未升高。TNFi暴露并未使恶性肿瘤风险增加超过未使用生物制剂的患者。与普通人群相比，接受TNFi治疗和未使用生物制剂的RA患者肺癌风险均增加，这表明RA状态或TNFi以外的RA治疗可能在某种程度上起作用。
