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Abstract：
Immune-mediated inflammatory diseases including rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), non-radiographic axial spondylarthritis (nr-axSpA), atopic dermatitis (AD), ulcerative colitis (UC), and Crohn\'s disease (CD) pose a substantial burden on patients and their quality of life. Upadacitinib is an orally administered, selective, and reversible Janus kinase inhibitor indicated for seven conditions, but data on its safety versus other active treatments are limited. A systematic literature review of indirect and direct treatment comparisons of randomized controlled trials (RCTs) was conducted to assess the safety profile of upadacitinib.
MEDLINE, Embase, and Cochrane Library databases were searched for indirect and direct treatment comparisons of RCTs that (1) included licensed upadacitinib dosages; (2) studied any of the seven conditions; (3) reported any adverse events (AEs), serious AEs (SAEs), AEs leading to discontinuation, major adverse cardiovascular event, venous thromboembolism, malignancies, infections or serious infections, and death; and (4) were published between January 2018 and August 2022.
A total of 25 studies were eligible for inclusion. SAEs, AEs leading to discontinuation, and any AEs were commonly studied. RA was the most studied condition, followed by AD and UC. Most studies (16/25, 64%) reported no statistically significant difference in the studied safety outcomes between upadacitinib and other active treatments (e.g., tumor necrosis factor blockers, interleukin receptor antagonists, integrin receptor antagonists, T cell co-stimulation modulator), or placebo (placebo ± methotrexate or topical corticosteroids). Other studies (9/25, 36%) reported mixed results of no statistically significant difference and either statistically higher (8/25, 32%) or lower rates (1/25, 4%) on upadacitinib.
Most studies suggested that upadacitinib has no statistically significant difference in the studied safety outcomes compared to active treatments or placebo in patients with RA, PsA, AS, AD, UC, and CD. A few studies reported higher rates, but findings were inconsistent with limited interpretation.
MEDLINE, Embase, and Cochrane Library databases were searched for indirect and direct treatment comparisons of RCTs that (1) included licensed upadacitinib dosages; (2) studied any of the seven conditions; (3) reported any adverse events (AEs), serious AEs (SAEs), AEs leading to discontinuation, major adverse cardiovascular event, venous thromboembolism, malignancies, infections or serious infections, and death; and (4) were published between January 2018 and August 2022.
A total of 25 studies were eligible for inclusion. SAEs, AEs leading to discontinuation, and any AEs were commonly studied. RA was the most studied condition, followed by AD and UC. Most studies (16/25, 64%) reported no statistically significant difference in the studied safety outcomes between upadacitinib and other active treatments (e.g., tumor necrosis factor blockers, interleukin receptor antagonists, integrin receptor antagonists, T cell co-stimulation modulator), or placebo (placebo ± methotrexate or topical corticosteroids). Other studies (9/25, 36%) reported mixed results of no statistically significant difference and either statistically higher (8/25, 32%) or lower rates (1/25, 4%) on upadacitinib.
Most studies suggested that upadacitinib has no statistically significant difference in the studied safety outcomes compared to active treatments or placebo in patients with RA, PsA, AS, AD, UC, and CD. A few studies reported higher rates, but findings were inconsistent with limited interpretation.
摘要：
背景：免疫介导的炎性疾病，包括类风湿性关节炎（RA），银屑病关节炎（PsA），强直性脊柱炎（AS），非影像学轴性脊椎关节炎（nr-axSpA），特应性皮炎(AD),溃疡性结肠炎（UC），克罗恩病（CD）对患者及其生活质量造成了沉重负担。Upadacitinib是一种口服给药，选择性,和可逆性Janus激酶抑制剂用于七个条件，但与其他积极治疗相比，其安全性数据有限。对随机对照试验（RCT）的间接和直接治疗比较进行了系统的文献综述，以评估upadacitinib的安全性。
方法：MEDLINE，Embase,和CochraneLibrary数据库搜索RCTs的间接和直接治疗比较，（1）包括许可的upadacitinib剂量；（2）研究了7种情况中的任何一种；（3）报告了任何不良事件（AE），严重不良事件（SAE），导致停药的不良事件，主要不良心血管事件，静脉血栓栓塞,恶性肿瘤,感染或严重感染，和死亡；（4）在2018年1月至2022年8月之间发布。
结果：共有25项研究符合纳入条件。SAEs,导致停药的不良事件，和任何AE都被普遍研究。RA是研究最多的疾病，其次是AD和UC。大多数研究（16/25，64％）报告了upadacitinib和其他积极治疗之间的研究安全性结果没有统计学上的显着差异（例如，肿瘤坏死因子阻滞剂，白细胞介素受体拮抗剂，整合素受体拮抗剂，T细胞共刺激调节剂），或安慰剂（安慰剂±甲氨蝶呤或外用皮质类固醇）。其他研究（9/25，36％）报告了混合结果，没有统计学上的显着差异，并且在统计上更高（8/25，32％）或更低的比率（1/25，4％）upadacitinib。
结论：大多数研究表明，与RA患者的积极治疗或安慰剂相比，upadacitinib在研究的安全性结果上没有统计学上的显着差异，PsA,AS,AD,UC,和CD。一些研究报告了更高的比率，但研究结果与有限的解释不一致.
方法：MEDLINE，Embase,和CochraneLibrary数据库搜索RCTs的间接和直接治疗比较，（1）包括许可的upadacitinib剂量；（2）研究了7种情况中的任何一种；（3）报告了任何不良事件（AE），严重不良事件（SAE），导致停药的不良事件，主要不良心血管事件，静脉血栓栓塞,恶性肿瘤,感染或严重感染，和死亡；（4）在2018年1月至2022年8月之间发布。
结果：共有25项研究符合纳入条件。SAEs,导致停药的不良事件，和任何AE都被普遍研究。RA是研究最多的疾病，其次是AD和UC。大多数研究（16/25，64％）报告了upadacitinib和其他积极治疗之间的研究安全性结果没有统计学上的显着差异（例如，肿瘤坏死因子阻滞剂，白细胞介素受体拮抗剂，整合素受体拮抗剂，T细胞共刺激调节剂），或安慰剂（安慰剂±甲氨蝶呤或外用皮质类固醇）。其他研究（9/25，36％）报告了混合结果，没有统计学上的显着差异，并且在统计上更高（8/25，32％）或更低的比率（1/25，4％）upadacitinib。
结论：大多数研究表明，与RA患者的积极治疗或安慰剂相比，upadacitinib在研究的安全性结果上没有统计学上的显着差异，PsA,AS,AD,UC,和CD。一些研究报告了更高的比率，但研究结果与有限的解释不一致.
