Liu-Yan Nie, Kun Zhao, Cheng Xu, Ming-Hao Liu, Xue-Xiao Jin, Yong-Mei Han
Department of Rheumatology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Center for Rehabilitation Medicine, Rehabilitation & Sports Medicine Research Institute of Zhejiang Province, Department of Rehabilitation Medicine, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China.
Heliyon. 2023 Jun 4;9(6):e17002. doi: 10.1016/j.heliyon.2023.e17002. eCollection 2023 Jun.
Upadacitinib (UPA), an oral Janus kinase (JAK) inhibitor, is an effective treatment option for rheumatoid arthritis (RA), but its use has been associated with an increased risk of digestive events. This systematic review aimed to investigate the risk of digestive events in RA patients treated with UPA.
Systematic searches of electronic databases (PubMed, Cochrane Library, and EMBASE) from inception to September 2022 were conducted to locate randomized controlled trials (RCTs) that compared UPA with control treatment and reported digestive events in RA patients. We pooled data using the random-effects model and meta-analysis was conducted by Stata software.
Ten RCTs met the inclusion criteria and were analyzed, with a total of 6103 patients. Compared with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), pooled analysis of 8 trials revealed no statistical difference in hepatic disorder (HD) risk and gastrointestinal (GI) perforation (GIP) risk ((OR = 1.16, 95% CI 0.86 to 1.56, I = 0.00%); OR = 4.49, 95% CI 0.56 to 35.93, I = 0.00%)). When we considered the influence of UPA on the grade of liver enzymes, the data indicated that grade 3 and 4 elevations in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were infrequent. Additionally, a dose-dependent impact of UPA on the risks of HD was not observed. The results suggested no interaction by dose of drug, or indication for treatment of GIP risk.
Our results showed that RA patients receiving UPA compared with csDMARDs had no significant increased risk associated with digestive events. Further long-term research of emerging data is urgently needed to gain a better understanding of the association between UPA and digestive events in the RA population.
乌帕替尼（UPA）是一种口服的 Janus 激酶（JAK）抑制剂，是类风湿关节炎（RA）的一种有效治疗选择，但其使用与消化事件风险增加有关。本系统评价旨在调查接受 UPA 治疗的 RA 患者发生消化事件的风险。
对电子数据库（PubMed、Cochrane 图书馆和 EMBASE）从创建至 2022 年 9 月进行系统检索，以查找比较 UPA 与对照治疗并报告 RA 患者消化事件的随机对照试验（RCT）。我们使用随机效应模型汇总数据，并通过 Stata 软件进行荟萃分析。
10 项 RCT 符合纳入标准并进行了分析，共有 6103 名患者。与传统合成抗风湿药物（csDMARDs）相比，对 8 项试验的汇总分析显示，肝脏疾病（HD）风险和胃肠道（GI）穿孔（GIP）风险无统计学差异（（OR = 1.16，95%CI 0.86 至 1.56，I = 0.00%）；OR = 4.49，95%CI 0.56 至 35.93，I = 0.00%））。当我们考虑 UPA 对肝酶水平的影响时，数据表明天冬氨酸转氨酶（AST）和丙氨酸转氨酶（ALT）3 级和 4 级升高并不常见。此外，未观察到 UPA 对 HD 风险有剂量依赖性影响。结果表明药物剂量与 GIP 风险的治疗指征之间无相互作用。
我们的结果表明，与 csDMARDs 相比，接受 UPA 治疗的 RA 患者发生消化事件的风险没有显著增加。迫切需要对新出现的数据进行进一步的长期研究，以更好地了解 UPA 与 RA 人群消化事件之间的关联。
