提示: 手机请竖屏浏览!

erenumab治疗发作性偏头痛的对照临床试验
A Controlled Trial of Erenumab for Episodic Migraine


Peter J. Goadsby ... 其他 • 2017.11.30
相关阅读
• 偏头痛 • 偏头痛和围手术期缺血性卒中的风险 • 病例总结:一名患偏头痛和发生行为变化的男性 • 病例7-2011:一例出现上呼吸道症状和低氧饱和度的52岁男性

摘要


背景

我们测试了erenumab预防发作性偏头痛的疗效。erenumab是一种可抑制降钙素基因相关肽受体的全人源单克隆抗体。

 

方法

我们随机分配患者接受erenumab皮下注射70 mg剂量、140 mg剂量或安慰剂,每月注射1次,共治疗6个月。主要终点是从第4至6个月,平均每月偏头痛天数相较于基线的变化。次要终点是平均每月偏头痛天数减少至少50%、急性偏头痛特异性药物用药天数的变化,以及偏头痛身体功能影响日志(Migraine Physical Function Impact Diary,MPFID)的身体障碍和日常活动维度评分的变化(量表评分范围转化为0~100分,评分较高表示偏头痛对身体功能产生的负担较重)。

 

结果

共955例患者经历了随机分组:317例分至70 mg erenumab组;319例分至140 mg erenumab组;319例分至安慰剂组。基线时总体人群的平均每月偏头痛天数为8.3日;截至第4至6个月时,70 mg erenumab组和140 mg erenumab组的平均每月偏头痛天数分别减少了3.2日和3.7日,而安慰剂组仅减少了1.8日(每个用药剂量组与安慰剂组相比P<0.001)。70 mg erenumab组和140 mg erenumab组中分别有43.3%和50.0%的患者平均每月偏头痛天数减少至少50%,而安慰剂组中这一比例仅为26.6%(每个用药剂量组与安慰剂组相比P<0.001);70 mg erenumab组和140 mg erenumab组急性偏头痛特异性药物的用药天数分别减少了1.1日和1.6日,而安慰剂组仅减少了0.2日(每个用药剂量组与安慰剂组相比P<0.001)。70 mg erenumab组和140 mg erenumab组的身体障碍评分分别降低了4.2分和4.8分,而安慰剂组仅降低了2.4分(每个用药剂量组与安慰剂组相比P<0.001);70 mg erenumab组和140 mg erenumab组的日常活动评分改善,分别降低5.5分和5.9分,而安慰剂组仅降低3.3分(每个用药剂量组与安慰剂组相比P<0.001)。erenumab和安慰剂组的不良事件发生率相似。

 

结论

在6个月的时间内,每月1次经皮下施用70 mg或140 mg剂量的erenumab,使偏头痛发作频率、偏头痛对日常活动的影响,以及急性偏头痛特异性药物的用药天数均出现了显著减少。erenumab的长期安全性和疗效持久性还需要进一步研究(由安进和诺华资助;STRIVE在ClinicalTrials.gov注册号为NCT02456740)。





作者信息

Peter J. Goadsby, M.D., Ph.D., Uwe Reuter, M.D., Yngve Hallström, M.D., Gregor Broessner, M.D., Jo H. Bonner, M.D., Feng Zhang, M.S., Sandhya Sapra, Ph.D., Hernan Picard, M.D., Ph.D., Daniel D. Mikol, M.D., Ph.D., and Robert A. Lenz, M.D., Ph.D.
From the National Institute for Health Research–Wellcome Trust King’s Clinical Research Facility, King’s College Hospital, London (P.J.G.); the Department of Neurology, Charité Universitätsmedizin Berlin, Berlin (U.R.); the Neuro Center, St. Göran Hospital, Stockholm (Y.H.); the Department of Neurology, Headache Outpatient Clinic, Medical University of Innsbruck, Innsbruck, Austria (G.B.); Mercy Research, St. Louis (J.H.B.); and the Departments of Global Biostatistical Science (F.Z.), Global Health Economics (S.S.), and Global Development (H.P., D.D.M., R.A.L.), Amgen, Thousand Oaks, CA. Address reprint requests to Dr. Goadsby at King’s College London, Wellcome Foundation Bldg., King’s College Hospital, London SE5 9PJ, United Kingdom, or at peter.goadsby@kcl.ac.uk.

 

参考文献

1. Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia 2013;33:629-808

2. Lipton RB, Manack Adams A, Buse DC, Fanning KM, Reed ML. A comparison of the Chronic Migraine Epidemiology and Outcomes (CaMEO) study and American Migraine Prevalence and Prevention (AMPP) study: demographics and headache-related disability. Headache 2016;56:1280-1289

3. Buse DC, Manack AN, Fanning KM, et al. Chronic migraine prevalence, disability, and sociodemographic factors: results from the American Migraine Prevalence and Prevention Study. Headache 2012;52:1456-1470

4. Goadsby PJ, Lipton RB, Ferrari MD. Migraine — current understanding and treatment. N Engl J Med 2002;346:257-270

5. Goadsby PJ, Sprenger T. Current practice and future directions in the prevention and acute management of migraine. Lancet Neurol 2010;9:285-298

6. Lipton RB, Bigal ME, Diamond M, Freitag F, Reed ML, Stewart WF. Migraine prevalence, disease burden, and the need for preventive therapy. Neurology 2007;68:343-349

7. Hepp Z, Dodick DW, Varon SF, Gillard P, Hansen RN, Devine EB. Adherence to oral migraine-preventive medications among patients with chronic migraine. Cephalalgia 2015;35:478-488

8. Charles A. Migraine: a brain state. Curr Opin Neurol 2013;26:235-239

9. Goadsby PJ, Edvinsson L, Ekman R. Vasoactive peptide release in the extracerebral circulation of humans during migraine headache. Ann Neurol 1990;28:183-187

10. Goadsby PJ, Edvinsson L. The trigeminovascular system and migraine: studies characterizing cerebrovascular and neuropeptide changes seen in humans and cats. Ann Neurol 1993;33:48-56

11. Lassen LH, Haderslev PA, Jacobsen VB, Iversen HK, Sperling B, Olesen J. CGRP may play a causative role in migraine. Cephalalgia 2002;22:54-61

12. Ho TW, Edvinsson L, Goadsby PJ. CGRP and its receptors provide new insights into migraine pathophysiology. Nat Rev Neurol 2010;6:573-582

13. Olesen J, Diener H-C, Husstedt IW, et al. Calcitonin gene–related peptide receptor antagonist BIBN 4096 BS for the acute treatment of migraine. N Engl J Med 2004;350:1104-1110

14. Ho TW, Ferrari MD, Dodick DW, et al. Efficacy and tolerability of MK-0974 (telcagepant), a new oral antagonist of calcitonin gene-related peptide receptor, compared with zolmitriptan for acute migraine: a randomised, placebo-controlled, parallel-treatment trial. Lancet 2008;372:2115-2123

15. Hewitt DJ, Aurora SK, Dodick DW, et al. Randomized controlled trial of the CGRP receptor antagonist MK-3207 in the acute treatment of migraine. Cephalalgia 2011;31:712-722

16. Diener HC, Barbanti P, Dahlöf C, Reuter U, Habeck J, Podhorna J. BI 44370 TA, an oral CGRP antagonist for the treatment of acute migraine attacks: results from a phase II study. Cephalalgia 2011;31:573-584

17. Marcus R, Goadsby PJ, Dodick D, Stock D, Manos G, Fischer TZ. BMS-927711 for the acute treatment of migraine: a double-blind, randomized, placebo controlled, dose-ranging trial. Cephalalgia 2014;34:114-125

18. Voss T, Lipton RB, Dodick DW, et al. A phase IIb randomized, double-blind, placebo-controlled trial of ubrogepant for the acute treatment of migraine. Cephalalgia 2016;36:887-898

19. Dodick DW, Goadsby PJ, Spierings ELH, Scherer JC, Sweeney SP, Grayzel DS. Safety and efficacy of LY2951742, a monoclonal antibody to calcitonin gene-related peptide, for the prevention of migraine: a phase 2, randomised, double-blind, placebo-controlled study. Lancet Neurol 2014;13:885-892

20. Dodick DW, Goadsby PJ, Silberstein SD, et al. Safety and efficacy of ALD403, an antibody to calcitonin gene-related peptide, for the prevention of frequent episodic migraine: a randomised, double-blind, placebo-controlled, exploratory phase 2 trial. Lancet Neurol 2014;13:1100-1107

21. Bigal ME, Dodick DW, Rapoport AM, et al. Safety, tolerability, and efficacy of TEV-48125 for preventive treatment of high-frequency episodic migraine: a multicentre, randomised, double-blind, placebo-controlled, phase 2b study. Lancet Neurol 2015;14:1081-1090

22. Sun H, Dodick DW, Silberstein S, et al. Safety and efficacy of AMG 334 for prevention of episodic migraine: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Neurol 2016;15:382-390

23. Shi L, Lehto SG, Zhu DX, et al. Pharmacologic characterization of AMG 334, a potent and selective human monoclonal antibody against the calcitonin gene-related peptide receptor. J Pharmacol Exp Ther 2016;356:223-231

24. Tepper S, Ashina M, Reuter U, et al. Safety and efficacy of erenumab for preventive treatment of chronic migraine: a randomised, double-blind, placebo-controlled phase 2 trial. Lancet Neurol 2017;16:425-434

25. Statistical principles for clinical trials. Geneva: International Conference on Harmonisation, February 1998.

26. Silberstein S, Tfelt-Hansen P, Dodick DW, et al. Guidelines for controlled trials of prophylactic treatment of chronic migraine in adults. Cephalalgia 2008;28:484-495

27. Adelman J, Freitag FG, Lainez M, et al. Analysis of safety and tolerability data obtained from over 1,500 patients receiving topiramate for migraine prevention in controlled trials. Pain Med 2008;9:175-185

28. Connor KM, Shapiro RE, Diener HC, et al. Randomized, controlled trial of telcagepant for the acute treatment of migraine. Neurology 2009;73:970-977

服务条款 | 隐私政策 | 联系我们