来利单抗联合甲氨蝶呤治疗活动性类风湿关节炎的疗效和安全性:为期56周的III期随机双盲安慰剂对照试验SOLAR结果

V. Mazurov, A. Lila, M. Korolev, A. Prystrom, A. Kundzer, N. Soroka, A. Kastanayan, T. Povarova, T. Plaksina, O. Antipova, D. Krechikova, S. Smakotina, O. Tciupa, E. V. Puntus, T. Raskina, L. Shilova, T. Kropotina, O. Nesmeyanova, T. Popova, I. Vinogradova, E. Dokukina, A. Plotnikova, P. Pukhtinskaia, A. Zinkina-Orikhan, Y. Linkova, A. Eremeeva, A. Lutckii, E. Nasonov
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The study was conducted at 21 clinical sites in Russia and Belarus. All randomized subjects have completed the study between November 2019 and October 2021.154 adults, aged ≥18 years with confirmed diagnosis of RA were randomly assigned (2:1) to receive either levilimab (162 mg, SC, QW) + MTX (n=102) or placebo + MTX (n=52).After W24 of the study all subjects continued to receive open label levilimab. Subjects who have achieved DAS28-CRP≤2.6 at W24 were switched to maintenance (Q2W) regimen of levilimab at W28 (LVL QW/Q2W and PBO/LVL Q2W arms). Those with DAS28-CRP>2.6 at W28 continued with QW regimen (LVL QW and PBO/LVL QW arm). The PBO/LVL Q2W arm contained only one subject, thus not included in the analysis. The efficacy analysis was done in a population of all randomized subjects. Those with missing data due to study discontinuation or rescue therapy prescription were considered non-responders. Otherwise, the analysis was performed on complete cases.Safety was assessed through monitoring of adverse events (AEs) in a population of those, who received at least on dose of LVL (n=152).Results. Better response to treatment was observed in LVL QW/Q2W as it composed of those who reach DAS28-CRP≤2.6 at W24. At this time point 15/27 (55.6%) of them achieved ACR70; 23/27 (85.2%) achieved DAS28-CRP remission (<2.6) and 7/27 (25.9%) achieved ACR/EULAR 2011 remission of RA. After switching to LVL Q2W, rates of ACR70 and DAS28-CRP<2.6 did not significantly changed until W52: 17/27 (63.0%) and 21/27 (77.8%), respectively, yet the proportion of subject with ACR/EULAR 2011 remission further increased and reached 12/27 (44.4%).LVL QW arm was diminished by subjects who achieved high response to treatment at W24 and composed LVL QW/Q2W arm. Thus, ACR70, and remissions rate in this arm was close to zero at W24. However, continuation of LVL QW in those who not achieved DAS28-CRP≤2.6 at W24 induced ACR70 response in 37/75 (36.0%), DAS28-CRP remission in 35/75 (46.7%) and ACR/EULAR 2011 remission in 8/75 (10.7%) at W52.The most common adverse events (reported in ≥5% of subjects) were blood cholesterol increase (30.3%), ALT increase (23.0%), lymphocyte count decrease (17.1%), ANC decrease (16.4%). blood triglycerides increase (13.8%), bilirubin increase (11.2%), AST increase (9.9%), WBC decrease (9.9%), IGRA with Mycobacterium tuberculosis antigen positive (7.2%) and injection site reactions (5.9%). No deaths were occurred.Conclusions. 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引用次数: 0

摘要

背景。此前,对活动性类风湿关节炎(RA)患者进行的为期24周的来伐利单抗III期双盲、安慰剂对照随机临床研究(SOLAR)结果证明,来伐利单抗优于安慰剂。在这里,我们介绍了SOLAR研究的1年疗效和安全性数据。目的评价来利莫单抗联合甲氨蝶呤(MTX)治疗甲氨蝶呤耐药活动性ra的疗效和安全性。这项研究在俄罗斯和白俄罗斯的21个临床地点进行。所有随机受试者都在2019年11月至2021年10月期间完成了研究。154名年龄≥18岁、确诊为RA的成年人被随机分配(2:1),接受来利单抗(162 mg, SC, QW) + MTX (n=102)或安慰剂+ MTX (n=52)。在研究的第24周之后,所有受试者继续接受开放标签的利伐单抗。在W24时DAS28-CRP≤2.6的受试者在W28时切换到利伐单抗维持(Q2W)方案(LVL QW/Q2W和PBO/LVL Q2W组)。在W28时DAS28-CRP为bb0 2.6的患者继续QW方案(LVL QW和PBO/LVL QW组)。PBO/LVL Q2W组仅包含1名受试者,因此未纳入分析。疗效分析是在所有随机受试者中进行的。那些由于研究中止或抢救治疗处方而丢失数据的患者被认为无反应。否则,对完整病例进行分析。通过监测不良事件(ae)来评估安全性,这些人群至少接受了一次LVL剂量(n=152)。LVL QW/Q2W组对治疗的反应更好,因为它由在W24时DAS28-CRP≤2.6的患者组成。此时15/27(55.6%)达到ACR70;23/27(85.2%)达到DAS28-CRP缓解(<2.6),7/27(25.9%)达到ACR/EULAR 2011缓解。切换到LVL Q2W后,ACR70和DAS28-CRP<2.6的比例分别在W52: 17/27(63.0%)和21/27(77.8%)前没有明显变化,但ACR/EULAR 2011缓解的受试者比例进一步增加,达到12/27(44.4%)。LVL QW组在24岁时对治疗有高反应并组成LVL QW/Q2W组的受试者减少。因此,在W24时,该组的ACR70和缓解率接近于零。然而,在W24时未达到DAS28-CRP≤2.6的患者继续LVL QW可诱导37/75的ACR70反应(36.0%),35/75的DAS28-CRP缓解(46.7%)和8/75的ACR/EULAR 2011缓解(10.7%)。最常见的不良事件(≥5%)是血胆固醇升高(30.3%)、ALT升高(23.0%)、淋巴细胞计数降低(17.1%)、ANC降低(16.4%)。血甘油三酯升高(13.8%),胆红素升高(11.2%),AST升高(9.9%),白细胞减少(9.9%),IGRA伴结核分枝杆菌抗原阳性(7.2%),注射部位反应(5.9%)。无死亡发生。开放标签期证实了对MTX耐药的活动性RA患者使用利来单抗联合MTX的持续有效性和安全性,并提示在第24周达到RA缓解的患者可以切换到维持(Q2W)方案。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Efficacy and safety of levilimab in combination with methotrexate in patients with active rheumatoid arthritis: 56-week results of phase III randomized double-blind placebo-controlled trial SOLAR
Background. Previously, 24-week results of phase III double-blind, placebo-controlled randomized clinical study (SOLAR) of levilimab in subjects with active rheumatoid arthritis (RA) proved a superiority of levilimab over placebo. Here we present 1-year efficacy and safety data of the SOLAR study.Objective – to evaluate the efficacy and safety of levilimab in combination with methotrexate (MTX) in subjects with MTX resistant active RA.Methods. The study was conducted at 21 clinical sites in Russia and Belarus. All randomized subjects have completed the study between November 2019 and October 2021.154 adults, aged ≥18 years with confirmed diagnosis of RA were randomly assigned (2:1) to receive either levilimab (162 mg, SC, QW) + MTX (n=102) or placebo + MTX (n=52).After W24 of the study all subjects continued to receive open label levilimab. Subjects who have achieved DAS28-CRP≤2.6 at W24 were switched to maintenance (Q2W) regimen of levilimab at W28 (LVL QW/Q2W and PBO/LVL Q2W arms). Those with DAS28-CRP>2.6 at W28 continued with QW regimen (LVL QW and PBO/LVL QW arm). The PBO/LVL Q2W arm contained only one subject, thus not included in the analysis. The efficacy analysis was done in a population of all randomized subjects. Those with missing data due to study discontinuation or rescue therapy prescription were considered non-responders. Otherwise, the analysis was performed on complete cases.Safety was assessed through monitoring of adverse events (AEs) in a population of those, who received at least on dose of LVL (n=152).Results. Better response to treatment was observed in LVL QW/Q2W as it composed of those who reach DAS28-CRP≤2.6 at W24. At this time point 15/27 (55.6%) of them achieved ACR70; 23/27 (85.2%) achieved DAS28-CRP remission (<2.6) and 7/27 (25.9%) achieved ACR/EULAR 2011 remission of RA. After switching to LVL Q2W, rates of ACR70 and DAS28-CRP<2.6 did not significantly changed until W52: 17/27 (63.0%) and 21/27 (77.8%), respectively, yet the proportion of subject with ACR/EULAR 2011 remission further increased and reached 12/27 (44.4%).LVL QW arm was diminished by subjects who achieved high response to treatment at W24 and composed LVL QW/Q2W arm. Thus, ACR70, and remissions rate in this arm was close to zero at W24. However, continuation of LVL QW in those who not achieved DAS28-CRP≤2.6 at W24 induced ACR70 response in 37/75 (36.0%), DAS28-CRP remission in 35/75 (46.7%) and ACR/EULAR 2011 remission in 8/75 (10.7%) at W52.The most common adverse events (reported in ≥5% of subjects) were blood cholesterol increase (30.3%), ALT increase (23.0%), lymphocyte count decrease (17.1%), ANC decrease (16.4%). blood triglycerides increase (13.8%), bilirubin increase (11.2%), AST increase (9.9%), WBC decrease (9.9%), IGRA with Mycobacterium tuberculosis antigen positive (7.2%) and injection site reactions (5.9%). No deaths were occurred.Conclusions. Open label period confirmed the lasting efficacy and safety of levilimab in combination with MTX in subjects with MTX resistant active RA and suggested the possibility of switching to maintenance (Q2W) regimen in those who achieved remission of RA at week 24.
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