在高频发作性偏头痛的随机 2 期研究中，用佛来美尼单抗起始治疗对头痛及相关症状的影响：治疗最初 3 周的事后分析。

The Effect of Beginning Treatment With Fremanezumab on Headache and Associated Symptoms in the Randomized Phase 2 Study of High Frequency Episodic Migraine: Post-Hoc Analyses on the First 3 Weeks of Treatment.

机构信息

Jefferson Headache Center, Thomas Jefferson University, Philadelphia, PA, USA.

David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.

出版信息

Headache. 2019 Mar;59(3):383-393. doi: 10.1111/head.13446. Epub 2018 Nov 18.

DOI:10.1111/head.13446

PMID:30450545

Abstract

BACKGROUND

Migraine has a substantial impact on daily living, affecting productivity and quality of life for patients and their families. Patients frequently discontinue preventive medications in part because of a delay in headache and symptom relief due to the long dose titration procedures necessary for some migraine preventives.

OBJECTIVE

To evaluate the efficacy of fremanezumab, a selective monoclonal CGRP ligand antibody, during the first 3 weeks of therapy in patients with high-frequency episodic migraine (HFEM) to relieve migraine headaches and associated symptoms and to reduce use of acute migraine medications.

METHODS

In a multicenter, randomized, double-blind, placebo-controlled, phase 2 study, patients with HFEM who met inclusion criteria and were 80% compliant with daily headache diary entry were randomized and treated once every 28 days for 3 months with either placebo or fremanezumab 225 or 675 mg. Compared to placebo, both doses of fremanezumab significantly reduced the primary endpoint of the HFEM study, change in the number of migraine days in month 3 relative to baseline. Herein, we performed post-hoc analyses to assess the efficacy of each dose during the first 3 weeks of treatment to reduce migraine headache parameters, associated migraine symptoms, and the consumption of acute migraine medications.

RESULTS

The sample consisted of 297 study participants. Compared to placebo, decreases in migraine days were seen during the first week of therapy for both fremanezumab doses with least square mean (LSM) differences between fremanezumab 225 mg and placebo of -0.93 (95% CI: -1.36, -0.49) and between 675 mg dose and placebo of -1.02 (95% CI: -1.46, -0.58), both P < .0001. This benefit was maintained through the second week of therapy for the 225 and 675 mg doses, respectively, (-0.76 (95% CI: -1.11, -0.40) P < .0001, -.79 (95% CI: -1.15, -0.44) P < .0001) and the third week of therapy (-0.64 (95% CI: -0.97, -0.30) P = .0003 and -0.64 (95% CI: -0.98, -0.30) P = .0003). Likewise in the first week, patients recorded reductions in associated migraine symptoms such as nausea, vomiting, photophobia, and phonophobia, which continued through weeks 2 and 3. There were also reductions in days with acute medication use to treat migraine for the 225 and 675 mg fremanezumab doses compared to placebo. In the first week, LSM differences between 225 mg and placebo were -1.02 (95% CI: -1.39, -0.64) and between 675 mg and placebo were -1.06 (95% CI: -1.39, -0.64) P < .0001); for the second and third weeks (-1.01 (95% CI: -1.14, -0.55) P < .0001; -.90 (95% CI: -1.04, -0.44) P < .0001; -.91 (95% CI: -0.92, -0.34) P < .0001; and -.83 (95% CI: -0.84, -0.26) P = .0002), respectively.

CONCLUSION

Fremanezumab treatment resulted in a rapid preventive response in patients with HFEM, with reductions seen in several headache parameters and migraine symptoms within the first week after therapy initiation and continuing during the second and third weeks. Patients also were able to rapidly reduce their use of acute medications to treat migraine attacks. The trial is registered at Clinicaltrials.gov as NCT02025556.

摘要

背景

偏头痛对日常生活有重大影响，影响患者及其家属的生产力和生活质量。由于某些偏头痛预防药物需要进行长时间的剂量滴定，患者经常会因头痛和症状缓解延迟而停止预防性药物治疗。

目的

评估选择性单克隆 CGRP 配体抗体依瑞奈珠单抗在高频发作性偏头痛（HFEM）患者中的疗效，以缓解偏头痛头痛和相关症状，并减少急性偏头痛药物的使用。

方法

在一项多中心、随机、双盲、安慰剂对照、2 期研究中，符合纳入标准且每日头痛日记记录率达到 80%的 HFEM 患者随机分组，每 28 天接受一次治疗，共 3 个月，分别接受安慰剂或依瑞奈珠单抗 225 或 675mg。与安慰剂相比，两种剂量的依瑞奈珠单抗均显著降低了 HFEM 研究的主要终点，即第 3 个月相对于基线的偏头痛天数变化。在此，我们进行了事后分析，以评估在治疗的前 3 周内，每种剂量对减少偏头痛头痛参数、相关偏头痛症状和急性偏头痛药物使用的疗效。

结果

研究样本包括 297 名研究参与者。与安慰剂相比，两种依瑞奈珠单抗剂量在治疗的第一周内均降低了偏头痛天数，依瑞奈珠单抗 225mg 与安慰剂相比的最小平方均数（LSMean）差异为-0.93（95%置信区间：-1.36，-0.49），675mg 剂量与安慰剂相比的差异为-1.02（95%置信区间：-1.46，-0.58），均 P<0.0001。这种益处在第 2 周和第 3 周的治疗中分别持续存在，225mg 和 675mg 剂量的差异分别为-0.76（95%置信区间：-1.11，-0.40），P<0.0001；-0.79（95%置信区间：-1.15，-0.44），P<0.0001）和第三周的治疗中（-0.64（95%置信区间：-0.97，-0.30），P=0.0003 和-0.64（95%置信区间：-0.98，-0.30），P=0.0003）。同样在第一周，患者记录到与偏头痛相关的症状（如恶心、呕吐、畏光和畏声）有所减轻，这些症状持续到第 2 周和第 3 周。与安慰剂相比，225mg 和 675mg 依瑞奈珠单抗剂量也减少了急性偏头痛药物的使用天数。在第一周，225mg 与安慰剂之间的 LSMean 差异为-1.02（95%置信区间：-1.39，-0.64），675mg 与安慰剂之间的差异为-1.06（95%置信区间：-1.39，-0.64），P<0.0001）；在第二周和第三周，差异分别为-1.01（95%置信区间：-1.14，-0.55），P<0.0001；-0.90（95%置信区间：-1.04，-0.44），P<0.0001；-0.91（95%置信区间：-0.92，-0.34），P<0.0001；和-0.83（95%置信区间：-0.84，-0.26），P=0.0002）。