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多发性硬化症中的β-干扰素疗法:临床相关剂量反应的证据

Interferon-beta therapy in multiple sclerosis: evidence for a clinically relevant dose response.

作者信息

Goodin D S

机构信息

Department of Neurology, University of California, San Francisco 94143-0114, USA.

出版信息

Drugs. 2001;61(12):1693-703. doi: 10.2165/00003495-200161120-00001.

Abstract

There have been considerable advances made recently in the treatment of multiple sclerosis (MS). In particular, interferon (IFN)beta has been demonstrated in several independent, multicentre clinical trials to lower unequivocally the biological activity of this illness. The results of these trials have been remarkably consistent, demonstrating a reduction in both disease activity and cumulative disability, using a combination of clinical and magnetic resonance imaging outcome measures. Nevertheless, the importance of the total weekly IFNbeta dose in the clinical management of individual patients has been controversial. However, there is considerable information available regarding the effect of IFNbeta dose on the various biochemical and clinical markers that are affected by IFNbeta, which is derived both from pre-clinical studies and multicentre clinical trials. On balance, convincing evidence is provided to support the notion that there is a clinically relevant dose-response in the use of IFNbeta to treat patients with relapsing/remitting MS. However, many of the clinical trials of IFNbeta in MS have confounded the potential effects of dose with the possible effects of frequency of IFNbeta administration. As a result, it is possible that the apparent dose-response observed in these clinical trials may be due, in part, to the more frequent dose administration schedule rather than the total weekly dose.

摘要

近年来,多发性硬化症(MS)的治疗取得了显著进展。特别是,干扰素(IFN)β已在多项独立的多中心临床试验中被明确证明可降低这种疾病的生物学活性。这些试验的结果非常一致,通过结合临床和磁共振成像结果测量方法,证明了疾病活动和累积残疾的减少。然而,每周总IFNβ剂量在个体患者临床管理中的重要性一直存在争议。然而,关于IFNβ剂量对受IFNβ影响的各种生化和临床标志物的作用,有大量信息可供参考,这些信息来自临床前研究和多中心临床试验。总的来说,有令人信服的证据支持这样一种观点,即在使用IFNβ治疗复发/缓解型MS患者时存在临床相关剂量反应。然而,许多MS中IFNβ的临床试验混淆了剂量的潜在影响与IFNβ给药频率的可能影响。因此,这些临床试验中观察到的明显剂量反应可能部分归因于更频繁的给药时间表,而不是每周总剂量。

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