i-NEED: NEw migrainE Drugs Database

Официальное название

Italian Real-life Multicenter Observational Study on Efficacy, Tolerability, and Safety of Innovative Drugs (Monoclonal Antibodies, Gepants, Ditans, Sumatriptan-naproxen) for Preventive or Acute Migraine Treatment.

Обзор

Approved by the Food and Drug Administration (FDA) and the European Medicine Agency (EMA) starting in 2018, anti-CGRP monoclonal antibodies (anti-CGRP mAbs) represent the first true revolution in the preventive treatment of migraine due to their selectivity and specificity. To date, four anti-CGRP mAbs have been developed for the preventive treatment of migraine: eptinezumab, erenumab, fremanezumab, and galcanezumab.Anti-CGRP mAbs constitute not only the first specific and selective treatment for the prevention of migraine but also the most extensively studied pharmacological category in this field, considering the vast and complex populations examined. The clinical effects of the various mAbs are substantially comparable and are characterized by several fundamental aspects: * High efficacy in both episodic and chronic migraine, with the presence of super-responders who experience a reduction in the average monthly number of migraine days of \>75% (or even 100%) compared to before treatment. * Efficacy that is independent of the clinical form of migraine - with or without aura - and regardless of whether there is analgesic overuse. * Efficacy maintained even in the presence of depressive or anxious comorbidities. * Rapid onset of action (even more pronounced with eptinezumab), with the therapeutic effect appearing within the first week in most cases. * Excellent tolerability with an absence of class-specific adverse events. * Outstanding treatment adherence and a very low rate of treatment discontinuation in the long term. It should also be noted that the development of anti-drug antibodies or neutralizing antibodies to anti-CGRP mAbs is rare and does not significantly impact the efficacy or tolerability of treatment. Future clinical practice will need to clarify several additional aspects, such as: 1) whether treatment with anti-CGRP mAbs can modify the course of migraine; 2) the appropriate approach regarding any traditional preventive treatment (whether to continue or discontinue it); 3) the definition of the characteristics of non-responders; 4) the definition of patients with a delayed response to treatment. Gepants are oral antagonists of the CGRP receptor. Among the four gepants synthesized so far (atogepant, rimegepant, ubrogepant, zavegepant), atogepant and rimegepant are currently available in Italy. Atogepant has proven to be an effective and well-tolerated option for the prevention of episodic and chronic migraines. Rimegepant is effective for both acute treatment and prevention of migraines, with a favorable safety profile and flexible oral administration. Lasmiditan is the first ditan effective for migraine attack and it represents a new therapeutic option for patients with contraindications to triptans, due to the presence of vascular risk factors, or for patients who experience undesirable side effects with these, thus increasing the therapeutic possibilities for the symptomatic treatment of migraine. The combination of sumatriptan 85 mg and naproxen sodium 500 mg is indicated for the acute treatment of migraine attacks in adult patients for whom sumatriptan monotherapy is insufficient.

Подробное описание

The European Headache Federation has published detailed guidelines on the state of the art regarding evidence of effectiveness in reducing the frequency and intensity of headache episodes, as well as the safety and tolerability of the four monoclonal antibodies under "ideal" experimental conditions, with patients selected based on stringent inclusion and exclusion criteria. This selection limits the direct transferability of the conclusions of these studies to clinical reality. Therefore, this study aims to evaluate, in a clinical practice setting, the real effectiveness in reducing the monthly frequency of migraine days and the tolerability and efficacy of monoclonal antibodies in a real-world evidence context. The study may later include all drugs that become available for this condition, subject to authorization by the competent Italian authority.

The present extension of the I-NEED study aims to integrate the collection and evaluation of real-life data on anti-CGRP monoclonal antibodies for migraine prophylaxis with the study of efficacy, safety, and tolerability-also in a real-world evidence context-of gepants in the prophylaxis of episodic and chronic migraine, and of rimegepant, ditans, and the sumatriptan-naproxen combination in the acute treatment of migraine.

Вмешательства

• Препарат anti-CGRP monoclonal antibodies
  erenumab, fremanezumab, galcanezumab, eptinezumab
• Препарат gepants
  atogepant, rimegepant
• Препарат combination of sumatriptan and naproxen
  combination of sumatriptan and naproxen
• Препарат ditan
  lasmiditan

Первичные конечные точки

• effectiveness of innovative drugs as migraine prophylaxis [Срок оценки: the assessment will be conducted at 4 weeks from treatment initiation]
• effectiveness of innovative drugs as migraine prophylaxis [Срок оценки: the assessment will be conducted at 8 weeks from treatment initiation]
• effectiveness of innovative drug as migraine prophylaxis [Срок оценки: the assessment will be conducted at 12 weeks from treatment initiation]
• effectiveness of innovative drugs as migraine prophylaxis [Срок оценки: the assessment will be conducted at 24 weeks from treatment initiation]
• effectiveness of innovative drugs as migraine prophylaxis [Срок оценки: the assessment will be conducted at 48 weeks from treatment initiation]
• 2 hour-pain freedom [Срок оценки: 2 hours]

Вторичные конечные точки (12)

• safety and tolerability of innovative drugs as migraine prophylaxis [Срок оценки: the assessment will be conducted at 48 weeks from treatment initiation]
• impact of innovative drugs as migraine prophylaxis on symptomatic medication use and medication overuse headache [Срок оценки: the assessment will be conducted at 48 weeks from treatment initiation]
• impact of innovative drugs as migraine prophylaxis on migraine symptoms [Срок оценки: the assessment will be conducted at 4 weeks from treatment initiation]
• impact of innovative drugs as migraine prophylaxis on migraine symptoms [Срок оценки: the assessment will be conducted at 8 weeks from treatment initiation]
• impact of innovative drugs as migraine prophylaxis on migraine symptoms [Срок оценки: the assessment will be conducted at 12 weeks from treatment initiation]
• impact of innovative drugs as migraine prophylaxis on migraine symptoms [Срок оценки: the assessment will be conducted at 24 weeks from treatment initiation]
• impact of innovative drugs as migraine prophylaxis on migraine symptoms [Срок оценки: the assessment will be conducted at 48 weeks from treatment initiation]
• impact of innovative drugs as migraine prophylaxis on migraine-related disability [Срок оценки: the assessment will be conducted at 4 weeks from treatment initiation]
• impact of innovative drugs as migraine prophylaxis on migraine-related disability [Срок оценки: the assessment will be conducted at 8 weeks from treatment initiation]
• impact of innovative drugs as migraine prophylaxis on migraine-related disability [Срок оценки: the assessment will be conducted at 12 weeks from treatment initiation]
• impact of innovative drugs as migraine prophylaxis on migraine-related disability [Срок оценки: the assessment will be conducted at 24 weeks from treatment initiation]
• impact of innovative drugs as migraine prophylaxis on migraine-related disability [Срок оценки: the assessment will be conducted at 48 weeks from treatment initiation]

Критерии участия

Критерии включения

• Age more or equal 18 years;
• Males and females;
• Willingness to sign the informed consent;
• Episodic migraine for the use of drug indicated for migraine attack
• High frequency episodic migraine, at least 8 days per month of disabling migraine in the past 3 months;
• Chronic migraine, according to the ICHD-III criteria;

Критерии исключения

• Other headaches different than migraine;
• Known intolerance to the eccipients;
• Vascular disease or Raynaud.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Италия · 2 центра

• Istituto Auxologico Italiano IRCCS — Milan
• IRCCS San Raffaele — Rome

Публикации

• Sacco S, Bendtsen L, Ashina M, Reuter U, Terwindt G, Mitsikostas DD, Martelletti P. European headache federation guideline on the use of monoclonal antibodies acting on the calcitonin gene related peptide or its receptor for migraine prevention. J Headache Pain. 2019 Jan 16;20(1):6. doi: 10.1186/s10194-018-0955-y. PMID 30651064
• Goadsby PJ, Reuter U, Hallstrom Y, Broessner G, Bonner JH, Zhang F, Sapra S, Picard H, Mikol DD, Lenz RA. A Controlled Trial of Erenumab for Episodic Migraine. N Engl J Med. 2017 Nov 30;377(22):2123-2132. doi: 10.1056/NEJMoa1705848. PMID 29171821
• Reuter U, Goadsby PJ, Lanteri-Minet M, Wen S, Hours-Zesiger P, Ferrari MD, Klatt J. Efficacy and tolerability of erenumab in patients with episodic migraine in whom two-to-four previous preventive treatments were unsuccessful: a randomised, double-blind, placebo-controlled, phase 3b study. Lancet. 2018 Nov 24;392(10161):2280-2287. doi: 10.1016/S0140-6736(18)32534-0. Epub 2018 Oct 22. PMID 30360965
• Stauffer VL, Dodick DW, Zhang Q, Carter JN, Ailani J, Conley RR. Evaluation of Galcanezumab for the Prevention of Episodic Migraine: The EVOLVE-1 Randomized Clinical Trial. JAMA Neurol. 2018 Sep 1;75(9):1080-1088. doi: 10.1001/jamaneurol.2018.1212. PMID 29813147
• Detke HC, Goadsby PJ, Wang S, Friedman DI, Selzler KJ, Aurora SK. Galcanezumab in chronic migraine: The randomized, double-blind, placebo-controlled REGAIN study. Neurology. 2018 Dec 11;91(24):e2211-e2221. doi: 10.1212/WNL.0000000000006640. Epub 2018 Nov 16. PMID 30446596
• Dodick DW, Silberstein SD, Bigal ME, Yeung PP, Goadsby PJ, Blankenbiller T, Grozinski-Wolff M, Yang R, Ma Y, Aycardi E. Effect of Fremanezumab Compared With Placebo for Prevention of Episodic Migraine: A Randomized Clinical Trial. JAMA. 2018 May 15;319(19):1999-2008. doi: 10.1001/jama.2018.4853. PMID 29800211
• Silberstein SD, Dodick DW, Bigal ME, Yeung PP, Goadsby PJ, Blankenbiller T, Grozinski-Wolff M, Yang R, Ma Y, Aycardi E. Fremanezumab for the Preventive Treatment of Chronic Migraine. N Engl J Med. 2017 Nov 30;377(22):2113-2122. doi: 10.1056/NEJMoa1709038. PMID 29171818
• Dodick DW, Goadsby PJ, Silberstein SD, Lipton RB, Olesen J, Ashina M, Wilks K, Kudrow D, Kroll R, Kohrman B, Bargar R, Hirman J, Smith J; ALD403 study investigators. 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 Nov;13(11) PMID 25297013

Идентификаторы

NCT: NCT07103694 · RP 22/02

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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