MS Center, Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands.
Ther Adv Neurol Disord. 2011 Jan;4(1):3-14. doi: 10.1177/1756285610391693.
To explore the effects of exposure to subcutaneous (sc) interferon (IFN) beta-1a on efficacy in patients with relapsing-remitting multiple sclerosis (RRMS) enrolled in the PRISMS (Prevention of Relapses and disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis) study.
Patients with RRMS received IFN beta-1a, 44 or 22 µg sc three times weekly (tiw), or placebo, for 2 years, at which point placebo recipients were re-randomized to IFN beta-1a, 44 or 22 µg sc tiw, for a further 2-4 years. Long-term follow-up visits occurred 7-8 years after enrolment and allowed participation of patients who had previously discontinued treatment. Post hoc descriptive analyses were conducted within the lower (MIN) and upper (MAX) quartiles of patients divided according to cumulative dose of IFN beta-1a and cumulative time on treatment. Outcomes were explored in patients initially randomized to IFN beta-1a, 44 µg sc tiw, who had received continuous or noncontinuous therapy during the study.
For both cumulative dose and time analyses, the MIN and MAX groups comprised 96 and 95 patients, respectively. The continuous and noncontinuous groups included 45 and 91 patients, respectively. The MAX DOSE and MAX TIME groups had lower annualized relapse rates, lower rates of conversion to secondary progressive MS, lower percentages of patients with Expanded Disability Status Scale progression, higher percentages of relapse-free patients, and less T2 burden of disease than the MIN groups. The continuous therapy group had a lower annualized relapse rate and lower percentages of patients with Expanded Disability Status Scale progression or conversion to secondary progressive MS than the noncontinuous therapy group.
The findings of these post hoc analyses suggest that high exposure to sc IFN beta-1a may be associated with better clinical outcomes than low exposure, and also highlight the importance of maximizing adherence. Additional prospective investigation is warranted to evaluate further the effects of treatment exposure on outcomes and to determine the benefits of interventions to improve adherence.
探索皮下（sc）干扰素（IFN）β-1a 暴露对 PRISMS（皮下干扰素β-1a 预防多发性硬化症复发和残疾）研究中复发缓解型多发性硬化症（RRMS）患者疗效的影响。
RRMS 患者接受 IFNβ-1a，44 或 22µg sc，每周 3 次（tiw），或安慰剂，为期 2 年，此时安慰剂接受者重新随机分配至 IFNβ-1a，44 或 22µg sc tiw，再持续 2-4 年。长期随访在入组后 7-8 年进行，并允许以前停止治疗的患者参与。根据 IFNβ-1a 的累积剂量和治疗时间，对患者进行按最低（MIN）和最高（MAX）四分位数的事后描述性分析。探索最初随机分配至 IFNβ-1a，44µg sc tiw 的患者的结局，这些患者在研究期间接受了连续或非连续治疗。
对于累积剂量和时间分析，MIN 和 MAX 组分别包括 96 和 95 名患者。连续和非连续组分别包括 45 和 91 名患者。MAX DOSE 和 MAX TIME 组的年复发率较低，向继发性进展型多发性硬化症（SPMS）转化的发生率较低，进展为扩展残疾状况量表（EDSS）的患者百分比较低，无复发患者的百分比较高，疾病的 T2 负荷较低，MIN 组。与非连续治疗组相比，连续治疗组的年复发率较低，EDSS 进展或向 SPMS 转化的患者百分比较低。
这些事后分析的结果表明，高 sc IFNβ-1a 暴露可能与更好的临床结局相关，而低暴露则相反，并且还强调了最大限度地提高依从性的重要性。需要进一步的前瞻性研究来进一步评估治疗暴露对结局的影响，并确定提高依从性的干预措施的益处。
