Department of Medicine, The University of Texas Southwestern Medical Center, Dallas, Texas, USA
Department of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama, USA.
Ann Rheum Dis. 2023 Sep;82(9):1130-1141. doi: 10.1136/ard-2023-223916. Epub 2023 Jun 12.
Increased risk of serious adverse events (AEs) was reported for tofacitinib relative to tumour necrosis factor inhibitor therapy in patients with rheumatoid arthritis (RA) aged ≥50 years enriched for cardiovascular (CV) risk (ORAL Surveillance). We assessed post hoc the potential risk of upadacitinib in a similar RA population.
Pooled safety data from six phase III trials were evaluated post hoc for AEs in patients receiving upadacitinib 15 mg once a day (with or without conventional synthetic disease-modifying antirheumatic drugs), adalimumab 40 mg every other week with concomitant methotrexate (MTX), or MTX monotherapy in the overall trial population and in a subset of patients with higher CV risk (aged ≥50 years, ≥1 CV risk factor). Higher-risk patients from a head-to-head study of upadacitinib 15 mg versus adalimumab (SELECT-COMPARE) were assessed in parallel. Exposure-adjusted incidence rates for treatment-emergent AEs were summarised based on exposure to upadacitinib or comparators.
A total of 3209 patients received upadacitinib 15 mg, 579 received adalimumab and 314 received MTX monotherapy; ~54% of the patients were included in the overall and SELECT-COMPARE higher-risk populations. Major adverse cardiovascular events (MACE), malignancy (excluding non-melanoma skin cancer (NMSC)) and venous thromboembolism (VTE) were more frequent in the higher-risk cohorts versus the overall population but were generally similar across treatment groups. Rates of serious infections in higher-risk populations and herpes zoster (HZ) and NMSC in all populations were higher with upadacitinib 15 mg than comparators.
An increased risk of MACE, malignancy (excluding NMSC) and VTE was observed in higher-risk populations with RA, yet risk was comparable between upadacitinib-treated and adalimumab-treated patients. Higher rates of NMSC and HZ were observed with upadacitinib versus comparators across all populations, and increased rates of serious infections were detected in upadacitinib-treated patients at higher CV risk.
NCT02706873, NCT02675426, NCT02629159, NCT02706951, NCT02706847 and NCT03086343.
在年龄≥50 岁且心血管（CV）风险较高的类风湿关节炎（RA）患者中，与肿瘤坏死因子抑制剂治疗相比，托法替布的严重不良事件（AE）风险增加（ORAL Surveillance）。我们在后分析中评估了乌帕替尼在类似 RA 人群中的潜在风险。
对六项 III 期试验的汇总安全性数据进行后分析，评估接受乌帕替尼 15mg 每日一次（联合或不联合常规合成疾病修饰抗风湿药物）、阿达木单抗 40mg 每两周一次联合甲氨蝶呤（MTX）或 MTX 单药治疗的患者的 AE 发生率。在总体试验人群和 CV 风险较高（年龄≥50 岁，≥1CV 风险因素）的亚组患者中评估来自乌帕替尼 15mg 与阿达木单抗头对头研究（SELECT-COMPARE）的高危患者。根据乌帕替尼或对照药物的暴露情况，总结治疗出现的 AE 的暴露调整发生率。
共 3209 例患者接受乌帕替尼 15mg 治疗，579 例患者接受阿达木单抗治疗，314 例患者接受 MTX 单药治疗；约 54%的患者纳入总体人群和 SELECT-COMPARE 高危人群。与总体人群相比，高危人群中主要不良心血管事件（MACE）、恶性肿瘤（不包括非黑色素瘤皮肤癌（NMSC））和静脉血栓栓塞症（VTE）更为常见，但在各治疗组之间通常相似。高危人群中乌帕替尼 15mg 治疗组的严重感染发生率和所有人群中带状疱疹（HZ）和 NMSC 发生率均高于对照药物。
在 RA 高危人群中观察到 MACE、恶性肿瘤（不包括 NMSC）和 VTE 的风险增加，但乌帕替尼治疗与阿达木单抗治疗患者之间的风险相当。与对照药物相比，所有人群中乌帕替尼治疗组的 NMSC 和 HZ 发生率更高，而高危 CV 风险的乌帕替尼治疗患者的严重感染发生率更高。
NCT02706873、NCT02675426、NCT02629159、NCT02706951、NCT02706847 和 NCT03086343。
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