Gottesman M H, Friedman-Urevich S
Winthrop University Hospital, Old Country Road, Mineola, NY 11501, USA.
Mult Scler. 2006 Jun;12(3):271-80. doi: 10.1191/135248506ms1261oa.
The approved interferon beta-1b (Betaseron/Betaferon) dose is 250 microg (8 MIU) administered subcutaneously (sc) every other day (eod). Clinical trial data suggest a dose response effect for interferon beta in multiple sclerosis (MS) treatment and a maximum dose has yet to be established. The Interferon Dose Escalation Assessment of Safety (IDEAS) study evaluated the safety and tolerability of interferon beta-1b 500 microg (16 MIU) sc eod with structured dose escalation and adverse event (AE) management in 22 patients (20 interferon beta-1b-treated (SD) and two interferon beta-1b-naïve (ND)) with relapsing-remitting (RR) MS, secondary-progressive (SP) MS, or progressive relapsing MS. IDEAS comprised an eight-week dose escalation period and a 12-week maintenance period, with modification as clinically warranted. Autoinjectors were used for all injections > or =0.4 mL. Clinical laboratory values were monitored monthly. Baseline and exit assessments included the MS Functional Composite score, EDSS, and neutralizing antibody MxA assay. AEs were recorded at every injection. Dose escalation ranged from two to 12 weeks. Some 91% of patients (20/22) achieved the 500-microg dose, and of these 90% (18/20) completed the maintenance phase. There were no differences in response between ND and SD patients. Most common AEs were decreased general well-being, insomnia, and injection site reactions (mostly mild). The 500-microg dose of interferon beta-1b was well tolerated in the short-term with escalation and premedication in these patients, most of whom had previously been receiving 250 microg interferon beta-1b.
已获批的干扰素β-1b（倍泰龙/β干扰素）剂量为250微克（8百万国际单位），每隔一天皮下注射一次。临床试验数据表明，干扰素β在治疗多发性硬化症（MS）方面存在剂量反应效应，且尚未确定最大剂量。干扰素剂量递增安全性评估（IDEAS）研究评估了22例复发缓解型（RR）MS、继发进展型（SP）MS或进展复发型MS患者（20例接受干扰素β-1b治疗（SD组）和2例未接受过干扰素β-1b治疗（ND组））使用500微克（16百万国际单位）干扰素β-1b皮下注射、每隔一天一次，并采用结构化剂量递增及不良事件（AE）管理的安全性和耐受性。IDEAS研究包括为期8周的剂量递增期和为期12周的维持期，并根据临床需要进行调整。所有≥0.4毫升的注射均使用自动注射器。每月监测临床实验室值。基线和结束评估包括MS功能综合评分、扩展残疾状态量表（EDSS）和中和抗体MxA检测。每次注射时记录AE。剂量递增持续2至12周。约91%的患者（20/22）达到了500微克的剂量，其中90%（18/20）完成了维持阶段。ND组和SD组患者的反应无差异。最常见的AE是总体健康状况下降、失眠和注射部位反应（大多为轻度）。在这些患者中，通过剂量递增和预处理，500微克剂量的干扰素β-1b在短期内耐受性良好，其中大多数患者之前接受的是250微克的干扰素β-1b。
