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 (N = 2451) and 49 malignancies after 2232 person-years in the biologic-naïve group (N = 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.

中文翻译：

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澳大利亚类风湿关节炎患者接受抗肿瘤坏死因子治疗的恶性肿瘤风险：来自澳大利亚风湿病协会数据库 (ARAD) 前瞻性队列研究的更新

肿瘤坏死因子抑制剂 (TNFi) 治疗已用于类风湿性关节炎 (RA) 患者数十年，但与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 治疗的患者与未接受生物制剂治疗的患者的癌症风险。2012 年 12 月 31 日之前在澳大利亚风湿病学协会数据库 (ARAD) 中登记的 RA 参与者的人口统计数据与 2016 年 5 月的国家癌症记录相匹配（与 2012 年的联系完成）。标准化发病率 (SIR) 用于比较 TNFi 暴露和未接受生物制剂的 ARAD 参与者与澳大利亚普通人群的恶性肿瘤发病率，使用日历年的地点、年龄和性别特异性比率。使用比率（RRs）比较暴露于 TNFi 的参与者和未接受生物制剂的 RA 患者的恶性肿瘤发病率，并根据年龄、性别、吸烟、甲氨蝶呤使用和先前的恶性肿瘤进行调整。在 TNFi 暴露组（N = 2451）和 2232 人年之后报告了 107 例恶性肿瘤（N = 574）和 49 例恶性肿瘤。与一般人群相比，未接受过生物制剂治疗的 RA 患者的总体恶性肿瘤风险增加 (SIR 1.52 (95% 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，未接受过生物制剂治疗和暴露于 TNFi 的患者的肺癌发病率均有所增加（分别为 SIR 2.69（95% CI 1.43 至 5.68）和 SIR 1.69（95% CI 1.05 至 2.90））。对于暴露于 TNFi 的患者，淋巴癌的风险增加（SIR 1.82, 95% CI 1.12, 3.18）。对于所检查的任何特定部位，暴露组之间的癌症风险没有差异。未接受过生物制剂治疗的 RA 患者的总体恶性肿瘤发病率升高，但暴露于 TNFi 的患者则没有。TNFi 暴露并未增加恶性肿瘤风险，超出未接受过生物制品治疗的患者的风险。与一般人群相比，接受 TNFi 治疗和未经生物制剂治疗的 RA 患者的肺癌风险均增加，这表明 RA 状态或 TNFi 以外的 RA 治疗可能在某种程度上是原因。未接受过生物制剂治疗的 RA 患者的总体恶性肿瘤发病率升高，但暴露于 TNFi 的患者则没有。TNFi 暴露并未增加恶性肿瘤风险，超出未接受过生物制品治疗的患者的风险。与一般人群相比，接受 TNFi 治疗和未经生物制剂治疗的 RA 患者的肺癌风险均增加，这表明 RA 状态或 TNFi 以外的 RA 治疗可能在某种程度上是原因。未接受过生物制剂治疗的 RA 患者的总体恶性肿瘤发病率升高，但暴露于 TNFi 的患者则没有。TNFi 暴露并未增加恶性肿瘤风险，超出未接受过生物制品治疗的患者的风险。与一般人群相比，接受 TNFi 治疗和未接受生物制剂治疗的 RA 患者的肺癌风险均增加，这表明 RA 状态或 TNFi 以外的 RA 治疗可能在某种程度上是原因。