Rieckmann Peter, Zivadinov Robert, Boyko Alexey, Selmaj Krzysztof, Alexander Jessica K, Kadosh Shaul, Rubinchick Svetlana, Bernstein-Hanlon Emily, Stark Yafit, Ashtamker Natalia, Davis Mat D, Khan Omar
Medical Park, Loipl, Germany.
Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, NY, USA.
Mult Scler J Exp Transl Clin. 2021 Dec 13;7(4):20552173211061550. doi: 10.1177/20552173211061550. eCollection 2021 Oct.
Describe the long-term outcomes of early-start (ES) and delayed-start (DS) glatiramer acetate 40 mg/mL treatment three times weekly (GA40) for up to seven years in the Glatiramer Acetate Low-frequency Administration (GALA) study in patients with relapsing multiple sclerosis (RMS).
Patients were evaluated every three to six months. The primary efficacy endpoint was annualized relapse rate (ARR); additional endpoints were exploratory or post hoc. For efficacy, data from the entire exposure period were used for the ES and DS cohorts. For safety, exposure only under GA40 was considered.
Of the patients who continued into the open-label extension (OLE), 580/834 (70%) ES and 261/419 (62%) DS completed the OLE. For the entire placebo-controlled and OLE study period, ARR was 0.26 for ES and 0.31 for DS patients (risk ratio = 0.83; 95% confidence interval [CI]: 0.70-0.99). ES prolonged median time to first relapse versus DS (4.9 versus 4.3 years; hazard ratio = 0.82; 95% CI: 0.6-0.96). OLE-only results showed DS patients experienced similar efficacy for relapse and disability outcomes as ES patients. Adverse events were consistent with the well-established GA safety profile.
GA40 treatment conferred clinical benefit up to seven years, resulting in sustained efficacy and was generally well tolerated in RMS patients.
在复发型多发性硬化症（RMS）患者的醋酸格拉替雷低频给药（GALA）研究中，描述起始剂量为40mg/mL的醋酸格拉替雷（GA40）每周三次、长达七年的早期起始（ES）和延迟起始（DS）治疗的长期结果。
每三至六个月对患者进行评估。主要疗效终点为年化复发率（ARR）；其他终点为探索性或事后分析终点。对于疗效，ES组和DS组使用整个暴露期的数据。对于安全性，仅考虑GA40治疗期间的暴露情况。
继续进入开放标签扩展期（OLE）的患者中，580/834（70%）的ES组和261/419（62%）的DS组完成了OLE。在整个安慰剂对照和OLE研究期间，ES组患者的ARR为0.26，DS组为0.31（风险比=0.83；95%置信区间[CI]：0.70-0.99）。与DS组相比，ES组延长了首次复发的中位时间（4.9年对4.3年；风险比=0.82；95%CI：0.6-0.96）。仅OLE期的结果显示，DS组患者在复发和残疾结局方面的疗效与ES组患者相似。不良事件与已确立的GA安全性特征一致。
GA40治疗在长达七年的时间里都能带来临床益处，疗效持续，且在RMS患者中总体耐受性良好。
