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口服降钙素基因相关肽受体拮抗剂rimegepant治疗偏头痛
Rimegepant, an Oral Calcitonin Gene–Related Peptide Receptor Antagonist, for Migraine


Richard B. Lipton ... 其他 • 2019.07.11
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• 偏头痛 • erenumab治疗发作性偏头痛的对照临床试验

摘要


背景

降钙素基因相关肽受体已被发现与偏头痛的发病机制有关。rimegepant是一种口服的降钙素基因相关肽受体小分子拮抗剂,可能能够有效治疗急性偏头痛。

 

方法

在一项多中心、双盲、3期试验中,我们将有至少1年偏头痛病史且每月有2~8次偏头痛中至重度发作的成人患者随机分组,分别口服75 mg rimegepant或匹配的安慰剂,用于治疗单次偏头痛发作。主要终点是无疼痛和无患者确定的最困扰症状(除疼痛之外),这两项终点均在rimegepant或安慰剂服药后2小时进行评估。

 

结果

共有1,186例患者被随机分组,分别接受rimegepant(594例患者)或安慰剂(592例患者)治疗;其中,rimegepant组537例患者和安慰剂组535例患者的疗效可评价。评价疗效患者的总体平均年龄为40.6岁,88.7%为女性。在改良意向治疗分析中,rimegepant组和安慰剂组服药后2小时无疼痛的患者比例分别为19.6%和12.0%(绝对差异,7.6个百分点;95%置信区间[CI],3.3~11.9;P<0.001)。rimegepant组和安慰剂组服药后2小时无最困扰症状的患者比例分别为37.6%和25.2%(绝对差异,12.4个百分点;95% CI,6.9~17.9;P<0.001)。最常见的不良事件为恶心和尿路感染。

 

结论

与安慰剂组相比,在口服降钙素基因相关肽受体拮抗剂rimegepant治疗偏头痛发作的患者中,无疼痛和无最困扰症状的患者比例较高(由Biohaven制药资助;在ClinicalTrials.gov注册号为NCT03237845)。





作者信息

Richard B. Lipton, M.D., Robert Croop, M.D., Elyse G. Stock, M.D., David A. Stock, Ph.D., Beth A. Morris, B.A., Marianne Frost, M.A., Gene M. Dubowchik, Ph.D., Charles M. Conway, Ph.D., Vladimir Coric, M.D., and Peter J. Goadsby, M.D., Ph.D.
From the Departments of Neurology and Epidemiology and Population Health, Albert Einstein College of Medicine, and Montefiore Medical Center — both in Bronx, NY (R.B.L.); Biohaven Pharmaceuticals, New Haven, CT (R.C., E.G.S., D.A.S., B.A.M., M.F., G.M.D., C.M.C., V.C.); NIHR–Wellcome Trust King’s Clinical Research Facility, King’s College Hospital–South London and Maudsley Biomedical Research Centre, King’s College London, London (P.J.G.); and the University of California, San Francisco, San Francisco (P.J.G.). Address reprint requests to Dr. Lipton at Montefiore Medical Center, Saul R. Korey Department of Neurology, Albert Einstein College of Medicine, 1165 Morris Park Ave., Bronx, NY 10461, or at richard.lipton@einstein.yu.edu. A list of investigators in this trial is provided in the Supplementary Appendix, available at NEJM.org.

 

参考文献

1. GBD 2016 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet 2017;390:1211-1259.

2. Lipton RB, Munjal S, Buse DC, et al. Allodynia is associated with initial and sustained response to acute migraine treatment: results from the American Migraine Prevalence and Prevention Study. Headache 2017;57:1026-1040.

3. Perry CM, Markham A. Sumatriptan: an updated review of its use in migraine. Drugs 1998;55:889-922.

4. Cortelli P, Allais G, Tullo V, et al. Frovatriptan versus other triptans in the acute treatment of migraine: pooled analysis of three double-blind, randomized, cross-over, multicenter, Italian studies. Neurol Sci 2011;32:Suppl 1:S95-S98.

5. Géraud G, Keywood C, Senard JM. Migraine headache recurrence: relationship to clinical, pharmacological, and pharmacokinetic properties of triptans. Headache 2003;43:376-388.

6. Derry CJ, Derry S, Moore RA. Sumatriptan (oral route of administration) for acute migraine attacks in adults. Cochrane Database Syst Rev 2012;2:CD008615-CD008615.

7. Gallagher RM, Kunkel R. Migraine medication attributes important for patient compliance: concerns about side effects may delay treatment. Headache 2003;43:36-43.

8. Buse DC, Reed ML, Fanning KM, Kurth T, Lipton RB. Cardiovascular events, conditions, and procedures among people with episodic migraine in the US population: results from the American Migraine Prevalence and Prevention (AMPP) Study. Headache 2017;57:31-44.

9. Lipton RB, Reed ML, Kurth T, Fanning KM, Buse DC. Framingham-based cardiovascular risk estimates among people with episodic migraine in the US population: results from the American Migraine Prevalence and Prevention (AMPP) Study. Headache 2017;57:1507-1521.

10. Goadsby PJ, Holland PR, Martins-Oliveira M, Hoffmann J, Schankin C, Akerman S. Pathophysiology of migraine: a disorder of sensory processing. Physiol Rev 2017;97:553-622.

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

12. 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.

13. 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.

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. 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.

16. 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.

17. 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.

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

19. Coric V, Stock EG, Pultz J, Marcus R, Sheehan DV. Sheehan Suicidality Tracking Scale (Sheehan-STS): Preliminary results from a multicenter clinical trial in generalized anxiety disorder. Psychiatry (Edgmont) 2009;6:26-31.

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