Matucci-Cerinic Marco, Allanore Yannick, Kavanaugh Arthur, Buch Maya H, Schulze-Koops Hendrik, Kucharz Eugeniusz J, Woehling Heike, Babic Goran, Poetzl Johann, Davis Adanna, Schwebig Arnd
Department of Experimental and Clinical Medicine, Division of Rheumatology AOUC, University of Florence, Florence, Italy.
Cochin Hospital, Rheumatology A Department, Paris Descartes University, Paris, France.
RMD Open. 2018 Nov 14;4(2):e000757. doi: 10.1136/rmdopen-2018-000757. eCollection 2018.
To demonstrate the equivalent efficacy and compare the safety and immunogenicity of an etanercept biosimilar, GP2015, with reference etanercept (ETN) in patients with moderate-to-severe, active rheumatoid arthritis (RA), characterised by an inadequate response to synthetic or biologic disease-modifying antirheumatic drugs (DMARDs).
In the EQUIRA study, eligible patients (n=376) were randomised 1: 1 to 50 mg GP2015 or ETN subcutaneously, once weekly, for 24 weeks (treatment period 1). Patients from both groups, with at least moderate European League Against Rheumatism response at week 24, received GP2015 up to week 48 (treatment period 2). All patients continued to receive concomitant methotrexate at a stable dose (10-25 mg/week) until end of the study. The 24-week results are presented here.
Equivalent efficacy between GP2015 and ETN was demonstrated if the 95% CI for the difference in disease activity score 28-joint count C reactive protein (DAS28-CRP) change from baseline to week 24 between treatment arms was contained within the prespecified equivalence margin range of -0.6 to 0.6. The least squares mean difference (GP2015-ETN) in change from baseline in DAS28-CRP up to week 24 was -0.07 (95% CI -0.26 to 0.12 [primary endpoint)]. The incidence of treatment-emergent adverse events was comparable between GP2015 (43.5%) and ETN (49.5%). None of the GP2015-treated patients developed neutralising anti-drug antibodies (NAbs) whereas 1.6% and 0.6% of patients in ETN group were NAb positive at weeks 4 and 12, respectively.
In patients with RA who had an inadequate response to DMARDs, GP2015 demonstrated a similar efficacy and a comparable safety and immunogenicity profile with ETN.
NCT02638259.
在对合成或生物性改善病情抗风湿药物（DMARDs）反应不足的中重度活动性类风湿关节炎（RA）患者中，证明依那西普生物类似药GP2015与参比依那西普（ETN）等效的疗效，并比较其安全性和免疫原性。
在EQUIRA研究中，符合条件的患者（n = 376）按1:1随机分为皮下注射50mg GP2015或ETN组，每周一次，共24周（治疗期1）。两组中在第24周时至少有中度欧洲抗风湿病联盟反应的患者，继续接受GP2015治疗至第48周（治疗期2）。所有患者持续接受稳定剂量（10 - 25mg/周）的甲氨蝶呤直至研究结束。此处展示的是24周的结果。
如果治疗组间从基线到第24周疾病活动评分28关节计数C反应蛋白（DAS28 - CRP）变化差异的95%置信区间包含在预先设定的等效界值范围-0.6至0.6内，则证明GP2015与ETN疗效等效。至第24周时，DAS28 - CRP从基线变化的最小二乘均值差异（GP2015 - ETN）为-0.07（95%置信区间-0.26至0.12[主要终点]）。GP2015组（43.5%）和ETN组（49.5%）治疗中出现的不良事件发生率相当。接受GP2015治疗的患者均未产生中和性抗药抗体（NAb），而ETN组分别有1.6%和0.6%的患者在第4周和第12周时NAb呈阳性。
在对DMARDs反应不足的RA患者中，GP2015显示出与ETN相似的疗效、相当的安全性和免疫原性。
NCT02638259
