复发缓解型多发性硬化症患者磁共振成像T2疾病负担的降低：来自EVIDENCE（干扰素剂量反应证据：欧美比较疗效）研究的48周数据分析

Reduction in magnetic resonance imaging T2 burden of disease in patients with relapsing-remitting multiple sclerosis: analysis of 48-week data from the EVIDENCE (EVidence of Interferon Dose-response: European North American Comparative Efficacy) study.

作者信息

Traboulsee A, Al-Sabbagh A, Bennett R, Chang P, Li D K B

机构信息

Division of Neurology, Medicine, University of British Columbia, Vancouver, BC, Canada.

出版信息

BMC Neurol. 2008 Apr 21;8:11. doi: 10.1186/1471-2377-8-11.

DOI:10.1186/1471-2377-8-11

PMID:18426595

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2374794/

Abstract

BACKGROUND

The EVIDENCE (EVidence of Interferon Dose-response: European North American Comparative Efficacy) study was an international, randomized, open-label, assessor-blinded, parallel-group study assessing the efficacy and tolerability of interferon (IFN) beta-1a, 44 mcg subcutaneously (sc) three times weekly (tiw), and IFN beta-1a, 30 mcg intramuscularly (im) once weekly (qw), in patients with relapsing-remitting multiple sclerosis (RRMS). The aim of this analysis was to assess whether reductions in T2 burden of disease (BOD) were greater for patients receiving IFN beta-1a, 44 mcg sc tiw, than for those treated with IFN beta-1a, 30 mcg im qw, and to assess the impact of neutralizing antibodies (NAbs).

METHODS

A post-hoc analysis was performed on magnetic resonance imaging (MRI) data collected prospectively from the EVIDENCE study. The analysis included all patients with evaluable T2 MRI scans at the start of dosing and at week 48, and those who received at least one drug dose (n = 553). Lesions were identified by a radiologist blinded to treatment codes and the total volume of T2 lesions (BOD) was reported in mm3.

RESULTS

Both median percentage decreases and absolute reduction in BOD were greater in the IFN beta-1a, 44 mcg sc tiw, treatment group. The adjusted mean treatment difference in percentage change in BOD from baseline to week 48 showed a significant treatment benefit for patients treated with IFN beta-1a, 44 mcg sc tiw, over those treated with IFN beta-1a, 30 mcg im qw (-4.6%; standard error: 2.6%; p = 0.002). The presence of NAbs reduced the effect of IFN beta-1a 44, mcg sc tiw, on BOD, but BOD changes were still similar to those seen with IFN beta-1a, 30 mcg im qw.

CONCLUSION

Patients with RRMS treated with IFN beta-1a, 44 mcg sc tiw, had greater reduction in T2 BOD after 48 weeks than those treated with IFN beta-1a, 30 mcg im qw, which is consistent with other clinical and MRI outcome measures in the EVIDENCE study. In patients testing positive for NAbs (NAb+) to IFN beta-1a 44 mcg sc tiw, changes in BOD were smaller than in NAb negative (NAb-) patients, but similar to those receiving IFN beta-1a, 30 mcg im qw.

摘要

背景

EVIDENCE（干扰素剂量反应的证据：欧美比较疗效）研究是一项国际、随机、开放标签、评估者盲法、平行组研究，旨在评估皮下注射（sc）44微克干扰素β-1a每周三次（tiw）和肌肉注射（im）30微克干扰素β-1a每周一次（qw）在复发缓解型多发性硬化症（RRMS）患者中的疗效和耐受性。本分析的目的是评估接受皮下注射44微克干扰素β-1a每周三次的患者，其T2疾病负担（BOD）的降低是否大于接受肌肉注射30微克干扰素β-1a每周一次的患者，并评估中和抗体（NAbs）的影响。

方法

对从EVIDENCE研究中前瞻性收集的磁共振成像（MRI）数据进行事后分析。分析包括所有在给药开始时和第48周有可评估T2 MRI扫描的患者，以及那些接受至少一剂药物的患者（n = 553）。由对治疗编码不知情的放射科医生识别病变，并以立方毫米报告T2病变的总体积（BOD）。

结果

皮下注射44微克干扰素β-1a每周三次的治疗组，BOD的中位数百分比下降和绝对减少量均更大。从基线到第48周，BOD百分比变化的调整后平均治疗差异显示，皮下注射44微克干扰素β-1a的患者比肌肉注射30微克干扰素β-1a的患者有显著的治疗益处（-4.6%；标准误差：2.6%；p = 0.002）。NAbs的存在降低了皮下注射44微克干扰素β-1a对BOD的作用，但BOD变化仍与肌肉注射30微克干扰素β-1a所见相似。

结论

皮下注射44微克干扰素β-1a每周三次治疗的RRMS患者，48周后T2 BOD的降低大于肌肉注射30微克干扰素β-1a每周一次治疗的患者，这与EVIDENCE研究中的其他临床和MRI结果指标一致。在对皮下注射44微克干扰素β-1a检测NAbs呈阳性（NAb+）的患者中，BOD的变化小于NAb阴性（NAb-）患者，但与接受肌肉注射30微克干扰素β-1a的患者相似。