Rheumatology Department, IDIS, Complejo Hospitalario Universitario de Santiago de Compostela, C/ Choupana s/n 15701, Santiago, Spain; Fundación Ramón Domínguez, IDIS, Complejo Hospitalario Universitario de Santiago de Compostela, Santiago, Spain.
Rheumatology Department, IDIS, Complejo Hospitalario Universitario de Santiago de Compostela, C/ Choupana s/n 15701, Santiago, Spain; Fundación Ramón Domínguez, IDIS, Complejo Hospitalario Universitario de Santiago de Compostela, Santiago, Spain.
Semin Arthritis Rheum. 2017 Oct;47(2):149-156. doi: 10.1016/j.semarthrit.2017.02.007. Epub 2017 Feb 16.
To summarize and compare the risks of malignancies accompanying biologic DMARDs (b-DMARDs) and tofacitinib in rheumatoid arthritis (RA) in randomized clinical trials (RCTs) and long-term extension studies (LTEs).
Articles in Medline, Embase, Cochrane Library, and the Web of Science dated from 2000 to February 2015. Selection criteria were as follows: (1) focus on RCTs or LTEs in RA; (2) treatment with b-DMARDs or tofacitinib; (3) data on malignancies; and (4) a minimum follow-up of 12 weeks. Data included publication details, study design, risk of bias, number and types of malignancies, and patient characteristics and treatments.
Of 113 articles and one updated report that were meta-analyzed, overall malignancies in RCTs showed odds ratio (95% confidence intervals) of 1.01 (0.72, 1.42) for all TNF antagonists, 1.12 (0.33, 3.81) for abatacept, 0.54 (0.20, 1.50) for rituximab, 0.70 (0.20, 2.41) for tocilizumab, and 2.39 (0.50, 11.5) for tofacitinib. Network meta-analysis of overall malignancies showed odds ratio (95% predictive intervals) of 1.68 (0.48-5.92) for infliximab, 0.79 (0.44-1.40) for etanercept, 0.93 (0.43-2.03) for adalimumab, 0.87 (0.28-2.75) for certolizumab, 0.87 (0.39-1.95) for golimumab, 1.04 (0.32-3.32) for abatacept, 0.58 (0.21-1.56) for rituximab, 0.60 (0.16-2.28) for tocilizumab, and 1.15 (0.24-5.47) for tofacitinib. Marginal numerical differences in the incidence rate of solid and hematological malignancies and non-melanoma skin cancers appeared in LTEs.
In RCTs, treatment of RA with b-DMARDs or tofacitinib does not increase the risk for malignancies. Generalizability of the differences in the rate of specific malignancies encountered in LTEs requires continuous pharmacovigilance of real-world patients.
总结并比较生物 DMARDs（b-DMARDs）和托法替尼治疗类风湿关节炎（RA）时的恶性肿瘤风险，并在随机临床试验（RCT）和长期扩展研究（LTEs）中进行比较。
检索 Medline、Embase、Cochrane 图书馆和 Web of Science 中 2000 年至 2015 年 2 月的文献。选择标准如下：（1）聚焦于 RA 的 RCT 或 LTE；（2）b-DMARDs 或托法替尼治疗；（3）恶性肿瘤数据；（4）至少 12 周的随访。数据包括出版物详细信息、研究设计、偏倚风险、恶性肿瘤的数量和类型，以及患者特征和治疗情况。
在对 113 篇文章和一份更新报告进行荟萃分析后，RCT 中总体恶性肿瘤的比值比（95%置信区间）为：所有 TNF 拮抗剂为 1.01（0.72，1.42），阿巴西普为 1.12（0.33，3.81），利妥昔单抗为 0.54（0.20，1.50），托珠单抗为 0.70（0.20，2.41），托法替尼为 2.39（0.50，11.5）。总体恶性肿瘤的网络荟萃分析显示，英夫利昔单抗的比值比（95%预测区间）为 1.68（0.48-5.92），依那西普为 0.79（0.44-1.40），阿达木单抗为 0.93（0.43-2.03），赛妥珠单抗为 0.87（0.28-2.75），戈利木单抗为 0.87（0.39-1.95），阿巴西普为 1.04（0.32-3.32），利妥昔单抗为 0.58（0.21-1.56），托珠单抗为 0.60（0.16-2.28），托法替尼为 1.15（0.24-5.47）。LTE 中观察到实体瘤和血液恶性肿瘤以及非黑色素瘤皮肤癌的发生率出现了微小的数值差异。
在 RCT 中，RA 采用 b-DMARDs 或托法替尼治疗不会增加恶性肿瘤的风险。LTE 中特定恶性肿瘤发生率差异的普遍性需要对真实世界患者进行持续的药物警戒。
