Flechter S, Vardi J, Pollak L, Rabey J M
The MS Clinical Research and Therapy Service, Department of Neurology, Assaf Harofeh Medical Center,, Zerifin 70300 Israel.
J Neurol Sci. 2002 May 15;197(1-2):51-5. doi: 10.1016/s0022-510x(02)00047-3.
To compare the clinical efficacy, as expressed by relapse rate and disability accumulation, and safety profile of glatiramer acetate (Copaxone; COP-1) and Interferon beta-1b (Betaferon; IFN beta - 1b) administered to multiple sclerosis patients during a 2-year follow-up on an open-label parallel design, as compared to their clinical condition in the 2-year period prior to treatment.
Copaxone and IFN beta - 1b have been recently introduced for the treatment of relapsing forms of MS. Both medications have been proven to have a relatively safe profile and are used extensively world-wide.
58 consecutive patients with relapsing forms of MS were enrolled from the MS out-patient clinic, during three months. After being informed in detail of the two approved treatment options existing at the time in Israel, the patients chose by themselves to receive either: (a) Copaxone 20 mg subcutaneously (sc) daily (Copaxone dly, 20 patients), or (b) Copaxone 20 mg sc alternate-day (Copaxone alt, 18 patients) or (c) IFN beta-1b 8 MIU sc in alternate day (20 patients). Mean relapse rate/year and mean EDSS/year were calculated for each group of patients during the 2 years prior to the onset of treatment, and during the year prior to the onset of treatment. Statistical significance was observed in the relapse rate in the year prior to the onset of treatment between the IFN beta -1b group and the two Copaxone groups (p = 0.05). This statistical difference has no effect on the overall data of the 2 years prior to starting the treatment and on the results. No statistical significance was observed in the total number of relapses, and on the 2-year relapse rate, prior to the onset of treatment. Mean relapse rate/year and mean EDSS/year were calculated for each group during the first and second year of treatment. Wilcoxon analysis for clinical data and chi-square for adverse events were applied.
The three groups were statistically comparable concerning mean relapse/year in the 2 years before the trial started and no statistical significance was observed among the three groups. A statistically significant reduction in the mean relapse rate in the 2 years after onset of treatment was observed in the three group of patients: Copaxone daily (dly) 1.1 +/- 0.6 (p = 0.0001); Copaxone alternate (alt) 0.9 +/- 0.6 (p = 0.0004) and IFN beta -1b 1.2 +/- 0.7 (p = 0.0001). Disability as expressed by EDSS score prior to the onset of treatment and after 2 years of treatment showed deterioration in the three groups although more significant in the Copaxone groups: Copaxone dly 3.3 +/- 1.4 to 3.8 +/- 1.6 (p = 0.007); Copaxone alt 2.4 +/- 1.1 to 2.8 +/- 1.3 (p=0.04); IFN beta - 1b 3.1 +/- 1.3 to 3.3 +/- 2.0 (N.S.). The most common adverse events reported were: (1) flu-like symptoms 7 pts (35%) in the IFN beta -1b group; 10 pts (26%) of the two Copaxone groups; (2) increased spasticity of lower limbs 3 pts (15%), only in the IFN beta -1b group; (3) site injection reaction (SIR): 16 SIR (80%) in the IFN beta -1b group; 12 SIR (67%) in the Copaxone alt group; 14 SIR (70%) in the Copaxone dly group; and (4) systemic reaction 3 pts (15%) in the IFN beta -1b group; 4 pts (22%) in the Copaxone alt group; 6 pts (30%) in the Copaxone dly group. Premature termination occurred in five patients treated with Copaxone (3 in the alternate group and 2 in the daily group).
The present study, despite the limitations of an open-label study, shows that Copaxone dly, Copaxone alt and IFN beta -1b treatment seem to be equally effective for the control of exacerbations in MS. The adverse event profile, as reported by the patients, was also similar. However, the adverse events profile registered indicated that Copaxone is somewhat less detrimental, whereas disability as measured by EDSS accumulation showed that the interferon beta - 1b patients demonstrated a slower progression of the disability.
在一项开放标签平行设计的2年随访中，比较醋酸格拉替雷（考帕松；COP-1）和干扰素β-1b（倍泰龙；IFNβ-1b）用于治疗多发性硬化症患者的临床疗效（以复发率和残疾累积表示）及安全性，与治疗前2年的临床状况进行对比。
考帕松和IFNβ-1b最近被用于治疗复发型多发性硬化症。这两种药物均已被证明具有相对安全的特性，并且在全球范围内广泛使用。
在三个月内，从多发性硬化症门诊连续招募了58例复发型多发性硬化症患者。在详细了解了以色列当时现有的两种批准治疗方案后，患者自行选择接受以下治疗：（a）每日皮下注射（sc）20mg考帕松（每日考帕松组，20例患者），或（b）隔日皮下注射20mg考帕松（隔日考帕松组，18例患者），或（c）隔日皮下注射8MIU IFNβ-1b（20例患者）。计算每组患者在治疗开始前2年以及治疗开始前1年的年平均复发率和年平均扩展残疾状态量表（EDSS）评分。在治疗开始前1年，IFNβ-1b组与两个考帕松组之间的复发率存在统计学差异（p = 0.05）。这种统计学差异对治疗开始前2年的总体数据和结果没有影响。在治疗开始前，复发总数和2年复发率方面未观察到统计学差异。计算每组患者在治疗的第一年和第二年的年平均复发率和年平均EDSS评分。对临床数据应用Wilcoxon分析，对不良事件应用卡方分析。
在试验开始前的2年中，三组患者的年平均复发率在统计学上具有可比性，三组之间未观察到统计学差异。在三组患者中均观察到治疗开始后2年的年平均复发率有统计学显著降低：每日考帕松组1.1±0.6（p = 0.0001）；隔日考帕松组0.9±0.6（p = 0.0004）；IFNβ-1b组1.2±0.7（p = 0.0001）。以治疗开始前和治疗2年后的EDSS评分表示的残疾情况在三组中均显示恶化，尽管在考帕松组中更为显著：每日考帕松组从3.3±1.4变为3.8±1.6（p = 0.007）；隔日考帕松组从2.4±1.1变为2.8±1.3（p = 0.04）；IFNβ-1b组从3.1±1.3变为3.3±2.0（无统计学意义）。报告的最常见不良事件为：（1）IFNβ-1b组7例患者（35%）出现类似流感症状；两个考帕松组共10例患者（26%）出现；（2）仅在IFNβ-1b组中，3例患者（15%）出现下肢痉挛增加；（3）注射部位反应（SIR）：IFNβ-1b组16例（80%）；隔日考帕松组12例（67%）；每日考帕松组14例（70%）；（4）IFNβ-1b组3例患者（15%）出现全身反应；隔日考帕松组4例患者（22%）出现；每日考帕松组6例患者（30%）出现。5例接受考帕松治疗的患者提前终止治疗（隔日组3例，每日组2例）。
本研究尽管存在开放标签研究的局限性，但表明每日考帕松组、隔日考帕松组和IFNβ-1b治疗在控制多发性硬化症病情加重方面似乎同样有效。患者报告的不良事件情况也相似。然而，记录的不良事件情况表明考帕松的损害较小，而以EDSS累积测量的残疾情况表明IFNβ-1b治疗的患者残疾进展较慢。
