McCormack Paul L, Scott Lesley J
Adis International Limited, Auckland, New Zealand.
CNS Drugs. 2004;18(8):521-46. doi: 10.2165/00023210-200418080-00004.
Interferon-beta-1b (Betaseron, Betaferon) is a non-glycosylated recombinant human interferon-beta approved for high-frequency, subcutaneous (SC) administration in the treatment of multiple sclerosis (MS). Its mechanism of action is unknown, but may involve modulation of the autoimmune pathogenic processes of MS. In a randomised, double-blind trial in patients with relapsing-remitting MS (RRMS), SC interferon-beta-1b 250 micro g (8 million International Units [MIU]) every other day reduced the annual relapse rate and increased the proportion of relapse-free patients compared with placebo. It also reduced relapse severity, hospitalisations, and disease activity assessed by magnetic resonance imaging (MRI), and increased the time to first relapse. Progression of disability showed a trend towards reduction relative to placebo and baseline, but did not reach statistical significance. SC interferon-beta-1b 250 micro g every other day was shown in a randomised trial to be superior to intramuscular (IM) interferon-beta-1a 30 micro g (6 MIU) once weekly with respect to reductions in relapse-related parameters, disability progression and MRI-assessed disease activity. In patients with secondary progressive MS (SPMS), SC interferon-beta-1b 250 micro g every other day slowed progression of the disease relative to placebo in one randomised, double-blind trial, but not in another. In both studies, interferon-beta-1b 250 micro g recipients had fewer relapses and less MRI-assessed disease activity than placebo recipients. The difference in primary outcome may reflect differences in patient entry criteria. Interferon-beta-1b is generally well tolerated and the common adverse events (e.g. injection site reactions, asthenia and an influenza-like symptom complex) are clinically manageable. In a randomised trial, the tolerability of SC interferon-beta-1b 250 micro g every other day was generally similar to that of IM interferon-beta-1a 30 micro g once weekly, except for higher incidences of injection site reactions and neutralising anti-interferon-beta antibodies with SC interferon-beta-1b. In conclusion, SC interferon-beta-1b 250 micro g every other day reduces the frequency and severity of relapses and MRI measures of disease activity and may delay the progression of disability in RRMS. The drug appeared to be more effective than, and as well tolerated as, IM interferon-beta-1a 30 micro g once weekly. Interferon-beta-1b also has positive effects on relapse rates and disease activity in patients with SPMS, although its effects on disease progression remain uncertain. The drug is generally well tolerated, and the common adverse events are clinically manageable. Thus, interferon-beta-1b is a valuable first-line therapy for patients with RRMS and a potentially useful option in those with SPMS.
干扰素β-1b(倍泰龙,Betaferon)是一种非糖基化的重组人干扰素β,已被批准用于高频皮下注射,以治疗多发性硬化症(MS)。其作用机制尚不清楚,但可能涉及对MS自身免疫致病过程的调节。在一项针对复发缓解型MS(RRMS)患者的随机双盲试验中,与安慰剂相比,每隔一天皮下注射250μg(800万国际单位[MIU])的干扰素β-1b可降低年复发率,并增加无复发患者的比例。它还降低了复发严重程度、住院率以及通过磁共振成像(MRI)评估的疾病活动度,并延长了首次复发时间。相对于安慰剂和基线,残疾进展呈下降趋势,但未达到统计学显著性。在一项随机试验中,每隔一天皮下注射250μg的干扰素β-1b在降低与复发相关的参数、残疾进展和MRI评估的疾病活动度方面优于每周一次肌肉注射30μg(6MIU)的干扰素β-1a。在一项随机双盲试验中,对于继发进展型MS(SPMS)患者,每隔一天皮下注射250μg的干扰素β-1b相对于安慰剂减缓了疾病进展,但在另一项试验中则没有。在这两项研究中,接受250μg干扰素β-1b治疗的患者比接受安慰剂治疗的患者复发次数更少,MRI评估的疾病活动度更低。主要结局的差异可能反映了患者入选标准的不同。干扰素β-1b一般耐受性良好,常见的不良事件(如注射部位反应、乏力和类流感症状复合体)在临床上是可控的。在一项随机试验中,每隔一天皮下注射250μg的干扰素β-1b的耐受性总体上与每周一次肌肉注射30μg的干扰素β-1a相似,只是皮下注射干扰素β-1b的注射部位反应和中和抗干扰素β抗体的发生率更高。总之,每隔一天皮下注射250μg的干扰素β-1b可降低复发频率和严重程度以及MRI评估的疾病活动度,并可能延缓RRMS患者的残疾进展。该药物似乎比每周一次肌肉注射30μg的干扰素β-1a更有效,且耐受性相当。干扰素β-1b对SPMS患者的复发率和疾病活动度也有积极影响,尽管其对疾病进展的影响仍不确定。该药物一般耐受性良好,常见的不良事件在临床上是可控的。因此,干扰素β-1b是RRMS患者有价值的一线治疗药物,对SPMS患者也是一个潜在的有用选择。