在类风湿关节炎中用乌帕替尼抑制结构性关节损伤进展：SELECT 3 期项目的 1 年结果。

Inhibition of structural joint damage progression with upadacitinib in rheumatoid arthritis: 1-year outcomes from the SELECT phase 3 program.

机构信息

Spire Sciences, Boca Raton, FL.

Division of Immunology and Rheumatology, Stanford University, Palo Alto, CA.

出版信息

Rheumatology (Oxford). 2022 Aug 3;61(8):3246-3256. doi: 10.1093/rheumatology/keab861.

OBJECTIVES

To evaluate the inhibition of progression of structural joint damage through week 48 in patients with moderately to severely active RA receiving upadacitinib as monotherapy or in combination with MTX.

METHODS

Radiographic progression was assessed in two phase 3 randomized controlled trials. MTX-naïve patients were randomized to upadacitinib 15 or 30 mg once daily or MTX monotherapy (SELECT-EARLY, n = 945), while MTX inadequate responders (IRs) were randomized to upadacitinib 15 mg once daily or adalimumab 40 mg every other week or placebo added to background MTX (SELECT-COMPARE, n = 1629). The mean changes from baseline in modified total Sharp score (mTSS), joint space narrowing and erosion scores were determined. Data were analysed both by linear extrapolation for missing data imputation and treatment switching and as observed.

RESULTS

In patients naïve or with limited exposure to MTX (SELECT-EARLY), mean changes from baseline to week 48 in mTSS were 0.03 for upadacitinib 15 mg, 0.14 for upadacitinib 30 mg and 1.00 for MTX based on linear extrapolation (P < 0.001 for both upadacitinib doses vs MTX). Among patients with an inadequate response to MTX (SELECT-COMPARE), the mean change from baseline in mTSS was significantly reduced in the upadacitinib 15 mg plus MTX group vs placebo plus MTX (0.28 vs 1.73; P < 0.001). The mean change from baseline in the adalimumab plus MTX group was 0.39.

CONCLUSION

Upadacitinib monotherapy or in combination with background MTX was effective in inhibiting the progression of structural joint damage through week 48 in MTX-naïve and MTX-IR patients with RA.

TRIAL REGISTRATION

ClinicalTrials.gov (https://clinicaltrials.gov), NCT02706873 and NCT02629159.

目的

评估中重度活动期 RA 患者接受乌帕替尼单药或联合 MTX 治疗 48 周时结构关节损伤进展的抑制情况。

方法

在两项 3 期随机对照试验中评估放射学进展。MTX 初治患者随机接受乌帕替尼 15 或 30mg 每日一次或 MTX 单药治疗（SELECT-EARLY，n=945），而 MTX 应答不足（IR）患者随机接受乌帕替尼 15mg 每日一次或阿达木单抗 40mg 每两周一次或安慰剂联合背景 MTX 治疗（SELECT-COMPARE，n=1629）。从基线到第 48 周时，测定改良总 Sharp 评分（mTSS）、关节间隙狭窄和侵蚀评分的平均变化。缺失数据插补和治疗转换的线性外推以及观察值均进行了数据分析。

结果

在 MTX 初治或有限暴露的患者中（SELECT-EARLY），乌帕替尼 15mg、30mg 和 MTX 从基线到第 48 周的 mTSS 平均变化值分别为 0.03、0.14 和 1.00（两种乌帕替尼剂量均显著优于 MTX，P<0.001）。在 MTX 应答不足的患者中（SELECT-COMPARE），乌帕替尼 15mg+MTX 组与安慰剂+MTX 组的 mTSS 从基线的平均变化显著降低（0.28 对 1.73；P<0.001）。阿达木单抗+MTX 组的平均变化值为 0.39。