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Abstract：
BACKGROUND: Rheumatoid arthritis (RA) is a systemic autoimmune disease. The combination therapy of methotrexate (MTX) and Janus kinase inhibitor (JAKi) is commonly used. Patients with RA are at increased risk of malignancy, however, it remains unclear whether the combination therapy is associated with a higher risk.
OBJECTIVE: To assess the malignancy risk among patients with RA receiving combination therapy of JAKi and MTX compared to MTX alone.
METHODS: PubMed, Cochrane and Embase were thoroughly searched for randomized controlled trials (RCTs) in patients with RA receiving JAKi and MTX, from inception to July 2020. Primary endpoints were malignancy events, Non melanomatous skin cancer (NMSC) and malignancy excluding NMSC and secondary endpoints were serious adverse events (SAE), deaths. Risk ratio (RR) and 95% CI were calculated using the Mantel-Haenszel random-effect method.
RESULTS: 659 publications were screened and 13 RCTs with a total of 6911 patients were included in the analysis. There was no statistically significant difference in malignancy [RR = 1.42; 95% CI (0.59, 3.41)], neither NMSC [RR = 1.44 (0.36, 5.76)] nor malignancies excluding NMSC [RR = 1.12 (0.40, 3.13)]. No statistically significant difference between the two groups for SAE [RR = 1.15 (0.90, 1.47)] and deaths [RR = 1.99 (0.75, 5.27)] was found.
CONCLUSIONS: The adjunction of JAKi to MTX is not associated with an increased risk of malignancy when compared to MTX alone. There is no increased risk of SAE and deaths when compared to MTX alone in patients with RA.
OBJECTIVE: To assess the malignancy risk among patients with RA receiving combination therapy of JAKi and MTX compared to MTX alone.
METHODS: PubMed, Cochrane and Embase were thoroughly searched for randomized controlled trials (RCTs) in patients with RA receiving JAKi and MTX, from inception to July 2020. Primary endpoints were malignancy events, Non melanomatous skin cancer (NMSC) and malignancy excluding NMSC and secondary endpoints were serious adverse events (SAE), deaths. Risk ratio (RR) and 95% CI were calculated using the Mantel-Haenszel random-effect method.
RESULTS: 659 publications were screened and 13 RCTs with a total of 6911 patients were included in the analysis. There was no statistically significant difference in malignancy [RR = 1.42; 95% CI (0.59, 3.41)], neither NMSC [RR = 1.44 (0.36, 5.76)] nor malignancies excluding NMSC [RR = 1.12 (0.40, 3.13)]. No statistically significant difference between the two groups for SAE [RR = 1.15 (0.90, 1.47)] and deaths [RR = 1.99 (0.75, 5.27)] was found.
CONCLUSIONS: The adjunction of JAKi to MTX is not associated with an increased risk of malignancy when compared to MTX alone. There is no increased risk of SAE and deaths when compared to MTX alone in patients with RA.
摘要：
背景：类风湿性关节炎（RA）是一种全身性自身免疫性疾病。通常使用甲氨蝶呤（MTX）和Janus激酶抑制剂（JAKi）的联合治疗。RA患者患恶性肿瘤的风险增加，然而,目前尚不清楚联合治疗是否与较高的风险相关.
目的：评估接受JAKi和MTX联合治疗的RA患者与单独使用MTX相比的恶性风险。
方法：PubMed，Cochrane和Embase在接受JAKi和MTX治疗的RA患者中进行了随机对照试验（RCT）的彻底搜索，从成立到2020年7月。主要终点是恶性肿瘤事件，非黑素瘤性皮肤癌（NMSC）和不包括NMSC的恶性肿瘤和次要终点是严重不良事件（SAE），死亡。使用Mantel-Haenszel随机效应法计算风险比(RR)和95%CI。
结果：对659篇出版物进行了筛选，并在分析中纳入了13个RCT，共6911名患者。恶性肿瘤差异无统计学意义[RR=1.42;95%CI(0.59,3.41)]。NMSC[RR=1.44(0.36,5.76)]和不包括NMSC的恶性肿瘤[RR=1.12(0.40,3.13)]。两组SAE[RR=1.15(0.90,1.47)]和死亡[RR=1.99(0.75,5.27)]无统计学差异。
结论：与单独使用MTX相比，JAKI与MTX的附加与恶性肿瘤风险增加无关。与单独使用MTX相比，RA患者的SAE和死亡风险没有增加。
目的：评估接受JAKi和MTX联合治疗的RA患者与单独使用MTX相比的恶性风险。
方法：PubMed，Cochrane和Embase在接受JAKi和MTX治疗的RA患者中进行了随机对照试验（RCT）的彻底搜索，从成立到2020年7月。主要终点是恶性肿瘤事件，非黑素瘤性皮肤癌（NMSC）和不包括NMSC的恶性肿瘤和次要终点是严重不良事件（SAE），死亡。使用Mantel-Haenszel随机效应法计算风险比(RR)和95%CI。
结果：对659篇出版物进行了筛选，并在分析中纳入了13个RCT，共6911名患者。恶性肿瘤差异无统计学意义[RR=1.42;95%CI(0.59,3.41)]。NMSC[RR=1.44(0.36,5.76)]和不包括NMSC的恶性肿瘤[RR=1.12(0.40,3.13)]。两组SAE[RR=1.15(0.90,1.47)]和死亡[RR=1.99(0.75,5.27)]无统计学差异。
结论：与单独使用MTX相比，JAKI与MTX的附加与恶性肿瘤风险增加无关。与单独使用MTX相比，RA患者的SAE和死亡风险没有增加。
