乌帕替尼与阿达木单抗治疗中重度类风湿关节炎患者的获益-风险分析
Benefit-Risk Analysis of Upadacitinib Compared with Adalimumab in the Treatment of Patients with Moderate-to-Severe Rheumatoid Arthritis.
作者信息
Conaghan Philip, Cohen Stanley, Burmester Gerd, Mysler Eduardo, Nash Peter, Tanaka Yoshiya, Rigby William, Patel Jayeshkumar, Shaw Tim, Betts Keith A, Patel Pankaj, Liu Jianzhong, Sun Rochelle, Fleischmann Roy
机构信息
Leeds Institute of Rheumatic and Musculoskeletal Medicine, National Institute for Health Research, Leeds Biomedical Research Centre-University of Leeds, Leeds, UK.
Metroplex Clinical Research Center, Dallas, TX, USA.
出版信息
Rheumatol Ther. 2022 Feb;9(1):191-206. doi: 10.1007/s40744-021-00399-5. Epub 2021 Nov 23.
INTRODUCTION
Rheumatoid arthritis (RA) is a chronic autoimmune disease requiring long-term treatment. Upadacitinib (UPA), a Janus kinase (JAK) inhibitor, is a new treatment for RA. The benefit-risk profile of a medication is best understood by evaluating the number needed to treat (NNT) and the number needed to harm (NNH). This analysis evaluated the comparative risk-benefit of UPA versus adalimumab (ADA).
METHODS
Post-hoc analyses were performed using data from the SELECT-COMPARE trial of UPA versus placebo (PBO) and UPA versus ADA among patients with active RA who remained on stable methotrexate (MTX) treatment and had an inadequate response; patients who failed to achieve response were rescued by predefined criteria-PBO or ADA switch to UPA, and UPA switch to ADA (all patients on PBO were switched to UPA at week 26). This analysis assessed efficacy and adverse events of special interest (AESIs) at week 26, 48, and 156 (3 years). NNT and NNH (95% confidence intervals) values were calculated between UPA versus ADA for all time points, and between UPA versus PBO for week 26. NNT and NNH values were applied to a hypothetical cohort of 100 patients to estimate the comparative efficacy and safety profiles.
RESULTS
UPA consistently showed greater efficacy than ADA, as evidenced by NNT values < 10 for achievement of Disease Activity Score in 28 joints based on C-reactive protein (DAS28-CRP) of < 2.6 and ≤ 3.2, respectively, and functional improvement. Based on indices for disease assessment other than the DAS28-CRP, remission outcomes were higher with UPA versus ADA over 26 weeks (NNTs: 7-12), 48 weeks (NNTs: 9-16), and 156 weeks (NNTs: 9-15). With the exception of herpes zoster, other AESIs demonstrated a similar risk with UPA versus ADA.
CONCLUSION
In patients with active RA despite MTX use, UPA demonstrated an incremental achievement of clinical outcomes compared to ADA together with a similar profile of AESIs with ADA (with the exception of herpes zoster).
引言
类风湿性关节炎（RA）是一种需要长期治疗的慢性自身免疫性疾病。乌帕替尼（UPA）是一种 Janus 激酶（JAK）抑制剂，是 RA 的一种新治疗方法。通过评估治疗所需人数（NNT）和伤害所需人数（NNH），能最好地了解药物的效益风险状况。本分析评估了 UPA 与阿达木单抗（ADA）的相对风险效益。
方法
使用 SELECT-COMPARE 试验的数据进行事后分析，该试验对比了 UPA 与安慰剂（PBO）以及 UPA 与 ADA，受试对象为仍在接受稳定甲氨蝶呤（MTX）治疗但反应不足的活动性 RA 患者；未达到反应的患者按预定义标准进行挽救——PBO 或 ADA 换用 UPA，以及 UPA 换用 ADA（所有接受 PBO 治疗的患者在第 26 周换用 UPA）。本分析评估了第 26 周、48 周和 156 周（3 年）时的疗效和特殊关注不良事件（AESIs）。计算了所有时间点 UPA 与 ADA 之间以及第 26 周时 UPA 与 PBO 之间的 NNT 和 NNH（95%置信区间）值。将 NNT 和 NNH 值应用于一个 100 名患者的假设队列，以估计相对疗效和安全性概况。
结果
UPA 始终显示出比 ADA 更高的疗效，基于 28 个关节疾病活动评分（基于 C 反应蛋白的 DAS28-CRP）分别达到<2.6 和≤3.2 以及功能改善的 NNT 值<10 可证明。基于除 DAS28-CRP 之外的疾病评估指标，在 26 周（NNT：7 - 12）、48 周（NNT：9 - 16）和 156 周（NNT：9 - 15）期间，UPA 与 ADA 相比缓解结局更高。除带状疱疹外，其他 AESIs 在 UPA 与 ADA 之间显示出相似的风险。
结论
在尽管使用 MTX 仍患有活动性 RA 的患者中，与 ADA 相比，UPA 在实现临床结局方面有增量改善，且与 ADA 的 AESIs 概况相似（带状疱疹除外）。
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