荷兰莱顿大学医学中心Michel D Ferrari课题组在研究中取得进展。他们比较了Fremanezumab（一种完全人源化的CGRP抗体）与安慰剂在偏头痛预防方面的疗效。2019年9月21日，国际知名医学期刊《柳叶刀》发表了这一成果。

研究组在比利时、捷克共和国、丹麦、芬兰、法国、德国、意大利、荷兰、波兰、西班牙、瑞典、瑞士、英国和美国的104个临床研究点进行了一项随机、双盲、安慰剂对照、平行组、临床3期试验。参与者为18-70岁患有阵发性或慢性偏头痛的患者，在过去10年中至少使用过2-4种药物，但均治疗失败。

2017年11月10日至2018年7月6日，课题组共招募了838名参与者，其中329名患阵发性偏头痛，509名患慢性偏头痛。按1：1：1分为三组，其中安慰剂组279名；季Fremanezumab组275名，3个月连续服用Fremanezumab；月Fremanezumab组283名，即第一个月服用Fremanezumab，第2、3个月服用安慰剂。

治疗12周后，与安慰剂组相比，季Fremanezumab组和月Fremanezumab组平均每月偏头痛天数显著减少。Fremanezumab的不良反应与安慰剂相似，三组的不良反应发生率均为1%左右 。

总之，对于曾经使用多达4种偏头痛预防药物均无效的难治性偏头痛患者，Fremanezumab疗效显著，且耐受性良好。

据悉，以降钙素基因相关肽（CGRP）或其受体为靶点的抗体可预防偏头痛发作。

附：英文原文

Title: Fremanezumab versus placebo for migraine prevention in patients with documented failure to up to four migraine preventive medication classes (FOCUS): a randomised, double-blind, placebo-controlled, phase 3b trial

Author: Michel D Ferrari, Hans Christoph Diener, Xiaoping Ning, Maja Galic, Joshua M Cohen, Ronghua Yang, Matthias Mueller, Andrew H Ahn, Yael Carmeli Schwartz, Melissa Grozinski-Wolff, Lindsay Janka, Messoud Ashina

Issue&Volume: 2019/09/21

Summary: 

Background

Antibodies targeting calcitonin gene-related peptide (CGRP) or its receptor have shown efficacy in the prevention of migraine attacks. We investigated the efficacy and tolerability of fremanezumab, a fully humanised CGRP antibody, in patients with migraine who had previously not responded to two to four classes of migraine preventive medications.

Methods

The randomised, double-blind, placebo-controlled, parallel-group, phase 3b FOCUS trial was done at 104 sites (including hospitals, medical centres, research institutes, and group practice clinics) across Belgium, the Czech Republic, Denmark, Finland, France, Germany, Italy, the Netherlands, Poland, Spain, Sweden, Switzerland, the UK, and the USA. We enrolled participants aged 18–70 years with episodic or chronic migraine who had documented failure to two to four classes of migraine preventive medications in the past 10 years. Failure was defined as no clinically meaningful improvement after at least 3 months of therapy at a stable dose, as per the treating physician's judgment; discontinuation because of adverse events that made treatment intolerable; or treatment contraindicated or unsuitable for the preventive treatment of migraine for the patient. Participants were randomly assigned (1:1:1) by electronic interactive response technology to subcutaneously administered quarterly fremanezumab (month 1, 675 mg; months 2 and 3: placebo), monthly fremanezumab (month 1: 225 mg in episodic migraine and 675 mg in chronic migraine; months 2 and 3: 225 mg in both migraine subgroups), or matched monthly placebo for 12 weeks. The primary outcome was mean change from baseline in the monthly average number of migraine days during the 12-week treatment period. This trial is registered with ClinicalTrials.gov, number NCT03308968, and is now completed.

Findings

Between Nov 10, 2017, and July 6, 2018, 838 participants with episodic (329 [39%]) or chronic (509 [61%]) migraine were randomly assigned to placebo (n=279), quarterly fremanezumab (n=276), or monthly fremanezumab (n=283). Reductions from baseline in monthly average migraine days over 12 weeks were greater versus placebo (least-squares mean [LSM] change −0·6 [SE 0·3]) with quarterly fremanezumab (LSM change −3·7 [0·3]; LSM difference vs placebo −3·1 [95% CI −3·8 to −2·4]; p<0·0001) and with monthly fremanezumab (LSM change −4·1 [0·34]; LSM difference vs placebo −3·5 [−4·2 to −2·8]; p<0·0001). Adverse events were similar for placebo and fremanezumab. Serious adverse events were reported in four (1%) of 277 participants with placebo, two (<1%) of 276 with quarterly fremanezumab, and four (1%) of 285 with monthly fremanezumab.

Interpretation

Fremanezumab was effective and well tolerated in patients with difficult-to-treat migraine who had previously not responded to up to four classes of migraine preventive medications.

DOI: 10.1016/S0140-6736(19)31946-4

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)31946-4/fulltext