PRISMS-4: Long-term efficacy of interferon-&bgr;-1a in relapsing MS
PRISMS-4: Long-term efficacy of interferon-&bgr;-1a in relapsing MS
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PRISMS-4：干扰素的长期疗效
DOI：
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发表时间：
2001
期刊：
影响因子：
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通讯作者：
G. Ebers
中科院分区：
文献类型：
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作者：
G. Rice;B. Paszner;J. Oger;J. Lesaux;D. Paty;G. Ebers
背景PRIMS研究显示，与安慰剂相比，干扰素-1a、22和44微克每周三次(TIW)在两年内对临床和MRI有显著的益处，在复发-缓解MS中，第三年和第四年的扩展研究结果被报道。方法最初接受安慰剂治疗的患者被随机分为干扰素-1a、22或44微克TIW(n=172；交叉组)，其余患者继续按原来分配的剂量盲法治疗，22微克(Rx22组)或44微克(Rx44组)TIW(n=167)。患者接受3至6个月的临床和年度MRI评估。结果4年复发率分别为1.02(交叉)、0.80(Rx22，p<；0.001)和0.72(Rx44，p<；0.001)，剂量效应接近显著(p=0.069；风险比，0.88；95%CI，0.76~1.01)。与安慰剂组(P<；0.001两种剂量)相比，交叉组的复发计数、核磁共振活动和干扰素-1a的病变负担累积均有所减少。与交叉组相比，Rx44组持续残疾进展的时间延长了18个月(p=0.047)。与交叉试验相比，Rx22和Rx44减少了新的T2病变数目和病变负担(p<；0.001)；在几个临床和核磁共振结果上，Rx44优于Rx22。14.3%(Rx44)和23.7%(Rx22)的患者出现持续中和抗体，并与疗效降低有关。结论两种剂量的临床和MRI益处持续了4年，并有剂量反应的证据。治疗4年的患者的结果始终好于交叉治疗组的患者。随着中和抗体的形成，疗效下降。
BackgroundThe PRISMS study demonstrated significant clinical and MRI benefit at 2 years for interferon-&bgr;-1a, 22 and 44 mcg thrice weekly (tiw), compared with placebo in relapsing–remitting MS. Years 3 and 4 extension study results are reported. MethodsPatients initially receiving placebo were randomized to blinded interferon-&bgr;-1a, 22 or 44 mcg tiw (n = 172; crossover group); others continued blinded treatment with their originally assigned dose, 22 mcg (Rx22 group) or 44 mcg (Rx44 group) tiw (n = 167 per group). Patients had 3- to 6-month clinical and annual MRI assessments. ResultsRelapse rates for 4 years were 1.02 (crossover), 0.80 (Rx22, p < 0.001), and 0.72 (Rx44, p < 0.001); the dose effect approached significance (p = 0.069; risk ratio, 0.88; 95% CI, 0.76–1.01). Crossover groups showed reductions in relapse count, MRI activity, and lesion-burden accumulation with interferon-&bgr;-1a compared with their placebo period (p < 0.001 both doses). Time to sustained disability progression was prolonged by 18 months in the Rx44 group compared with the crossover group (p = 0.047). Rx22 and Rx44 reduced new T2 lesion number and lesion burden compared with crossover (p < 0.001); Rx44 was superior to Rx22 on several clinical and MRI outcomes. Persistent neutralizing antibodies developed in 14.3% (Rx44) and 23.7% (Rx22) of patients and were associated with reduced efficacy. ConclusionsClinical and MRI benefit continued for both doses up to 4 years, with evidence of dose response. Outcomes were consistently better for patients treated for 4 years than for patients in crossover groups. Efficacy decreased with neutralizing antibody formation.