European headache federation consensus on the definition of resistant and refractory migraine : Developed with the endorsement of the European Migraine & Headache Alliance (EMHA)

Simona Sacco, Mark Braschinsky, Anne Ducros, Christian Lampl, Patrick Little, Antoinette Maassen van den Brink, Patricia Pozo-Rosich, Uwe Reuter, Elena Ruiz de la Torre, Margarita Sanchez Del Rio, Alexandra J Sinclair, Zaza Katsarava, Paolo Martelletti, Simona Sacco, Mark Braschinsky, Anne Ducros, Christian Lampl, Patrick Little, Antoinette Maassen van den Brink, Patricia Pozo-Rosich, Uwe Reuter, Elena Ruiz de la Torre, Margarita Sanchez Del Rio, Alexandra J Sinclair, Zaza Katsarava, Paolo Martelletti

Abstract

Introduction: Despite advances in the management of headache disorders, some patients with migraine do not experience adequate pain relief with acute and preventive treatments. It is the aim of the present document to provide a definition of those migraines which are difficult-to-treat, to create awareness of existence of this group of patients, to help Healthcare Authorities in understanding the implications, and to create a basis to develop a better pathophysiological understanding and to support further therapeutic advances.

Main body: Definitions were established with a consensus process using the Delphi method. Patients with migraine with or without aura or with chronic migraine can be defined as having resistant migraine and refractory migraine according to previous preventative failures. Resistant migraine is defined by having failed at least 3 classes of migraine preventatives and suffer from at least 8 debilitating headache days per month for at least 3 consecutive months without improvement; definition can be based on review of medical charts. Refractory migraine is defined by having failed all of the available preventatives and suffer from at least 8 debilitating headache days per month for at least 6 consecutive months. Drug failure may include lack of efficacy or lack of tolerability. Debilitating headache is defined as headache causing serious impairment to conduct activities of daily living despite the use of pain-relief drugs with established efficacy at the recommended dose and taken early during the attack; failure of at least two different triptans is required.

Conclusions: We hope, that the updated EHF definition will be able to solve the conflicts that have limited the use of definitions which have been put forward in the past. Only with a widely accepted definition, progresses in difficult-to-treat migraine can be achieved. This new definition has also the aim to increase the understanding of the impact of the migraine as a disease with all of its social, legal and healthcare implications. It is the hope of the EHF Expert Consensus Group that the proposed criteria will stimulate further clinical, scientific and social attention to patients who suffer from migraine which is difficult-to-treat.

Keywords: Chronic migraine; Intractable migraine; Migraine; Refractory migraine; Resistant migraine.

Conflict of interest statement

Mark Braschinsky: Fees as a speaker or for participation to advisory boards from Abbott Laboratories, Allergan Inc., Berlin-Chemie AG (Menarini Group), Boehringer Ingelheim Pharma GmbH, Desitin Arzneimittel GmbH, EV3, Gedeon Richter Ltd., GlaxoSmithKline, KBM Pharma Ltd., H. Lundbeck A/S, Novartis Pharma Services Inc., Nycomed SEFA, Orion Pharma, Pfizer Inc., Sanofi-Aventis, Sandoz d.d., Scanmed Group, Solvay Pharmaceuticals, Teva Pharmaceutical Industries Ltd./Sicor Biotech UAB, Zentiva International. Previously consultant for H. AbbePharma GmbH, Merz Pharmaceuticals.

Anne Ducros: Fees as speaker or participation to advisory boards from Eli-Lilly, Novartis, Teva.

Zaza Katsarava: Fees as speaker or participation to advisory boards from Novartis, Lilly, TEVA, Allergan, Merck and Daiichi.

Christian Lampl: Fees as speaker or for participation to advisory boards from Allergan, Eli-Lilly, Novartis, Pfizer, Teva.

Patrick Little: none.

Paolo Martelletti: Fees as speaker or for participation to advisory boards from Allergan, Eli-Lilly, Novartis, Teva.

Antoinette Massen van den Brink: Research grant and/or speaker/consultant fees from Amgen/Novartis, Eli-Lilly, Teva.

Patricia Pozo-Rosich: Fees as consultant and speaker for Allergan, Almirall, Biohaven, Chiesi, The Corpus, Eli Lilly, Medscape, Neurodiem, Novartis and Teva. Researchh funding from Allergan, AGAUR, la Caixa foundation, Migraine Research Foundation, Instituto Investigación Carlos III, MICINN, Novartis, PERIS, ERANet Neuron; funding for clinical trials from Alder, Electrocore, Eli Lilly, Novartis and Teva.

Uwe Reuter: Fees as consultant and speaker for Allergan, Biohaven, The Corpus, Eli Lilly, Medscape, Novartis, STREAMedUP and Teva. Research funding from BMBF and Novartis, Institutional funding for clinical trials from Alder, Amgen. Allergan, Eli Lilly, Novartis and Teva.

Elena Ruiz de la Torre: none.

Simona Sacco: Fees as speaker or for participation to advisory boards from Abbott, Allergan, Eli-Lilly, Medscape, Novartis, Teva.

Margarita Sanchez Del Rio: Fees as speaker or for participation to advisory boards from Allergan, Eli-Lilly, Novartis, Teva.

Alexandra J Sinclair: Fees as speaker from Novartis and Allergan.

References

    1. D'Antona L, Matharu M. Identifying and managing refractory migraine: barriers and opportunities? J Headache Pain. 2019;23:20.
    1. Goadsby PJ, Schoenen J, Ferrari MD, Silberstein SD, Dodick D. Towards a definition of intractable headache for use in clinical practice and trials. Cephalalgia. 2006;26:1168–1170.
    1. Martelletti P, Katsarava Z, Lampl C, Magis D, Bendtsen L, Negro A, Russell MB, Mitsikostas DD, Jensen RH. Refractory chronic migraine: a consensus statement on clinical definition from the European headache federation. J Headache Pain. 2014;15:47.
    1. Schulman EA, Lake AE, 3rd, Goadsby PJ, Peterlin BL, Siegel SE, Markley HG, Lipton RB. Defining refractory migraine and refractory chronic migraine: proposed criteria from the refractory headache special interest section of the American headache society. Headache. 2008;48:778–782.
    1. Silberstein SD, Dodick DW, Pearlman S. Defining the pharmacologically intractable headache for clinical trials and clinical practice. Headache. 2010;50:1499–1406.
    1. Wöber C, Wessely P, Austrian Consensus Group on Refractory Chronic Migraine Comment on: Martelletti et al. Refractory chronic migraine: a consensus statement on clinical definition from the European Headache Federation. J Headache Pain. 2014;15:77.
    1. Headache Classification Subcommittee of The International Headache Society The international classification of headache disorders 3rd edition. Cephalalgia. 2018;38:1–211.
    1. Dalkey NC, Helmer-Hirschberg O. An experimental application of the Delphi method to the use of experts. Santa Monica: Rand Corp; 1962.
    1. von der Gracht HA. Consensus measurement in Delphi studies: review and implications for future quality assurance. Technol Forecast Social Change. 2013;79:1525–1536.
    1. Katsarava Z, Schneeweiss S, Kurth T, Kroener U, Fritsche G, Eikermann A, Diener HC, Limmroth V. Incidence and predictors for chronicity of headache in patients with episodic migraine. Neurology. 2004;62:788–790.
    1. Lampl C, Jensen R, Martelletti P, Mitsikostas DD. Refractory headache: one term does not cover all--a statement of the European headache federation. J Headache Pain. 2014;15:50.
    1. Tassorelli C, Diener HC, Dodick DW, Silberstein SD, Lipton RB, Ashina M, Becker WJ, Ferrari MD, Goadsby PJ, Pozo-Rosich P, Wang SJ; International Headache Society Clinical Trials Standing Committee Guidelines of the international headache society for controlled trials of preventive treatment of chronic migraine in adults. Cephalalgia. 2018;38:815–832.
    1. Bendtsen L, Sacco S, Ashina M, Mitsikostas DD, Ahmed F, Pozo-Rosich P, Martelletti P. Guideline on the use of onabotulinumtoxinA in chronic migraine: a consensus statement from the European headache federation. J Headache and Pain. 2018;19:91.
    1. Martelletti P, Schwedt TJ, Lanteri-Minet M, Quintana R, Carboni V, Diener HC, Ruiz de la Torre E, Craven A, Rasmussen AV, Evans S, Laflamme AK, Fink R, Walsh D, Dumas P, Vo P. My migraine voice survey: a global study of disease burden among individuals with migraine for whom preventive treatments have failed. J Headache Pain. 2018;19:115.
    1. Silberstein SD, Lee L, Gandhi K, Fitzgerald T, Bell J, Cohen JM. Health care resource utilization and migraine disability along the migraine continuum among patients treated for migraine. Headache. 2018;58:1579–1592.
    1. Torres-Ferrus M, Quintana M, Fernandez-Morales J, Alvarez-Sabin J, Pozo-Rosich P. When does chronic migraine strike? A clinical comparison of migraine according to the headache days suffered per month. Cephalalgia. 2017;37:104–113.
    1. Marmura MJ, Silberstein SD, Schwedt TJ. The acute treatment of migraine in adults: the american headache society evidence assessment of migraine pharmacotherapies. Headache. 2015;55:3–20.
    1. Lampl C, Thomas H, Tassorelli C, Katsarava Z, Laínez JM, Lantéri-Minet M, Rastenyte D, Ruiz de la Torre E, Stovner LJ, Andrée C, Steiner TJ. Headache, depression and anxiety: associations in the Eurolight project. J Headache Pain. 2016;17:59.
    1. Lipton RB, Stewart WF, Sawyer J, Edmeads JG. Clinical utility of an instrument assessing migraine disability: the migraine disability assessment (MIDAS) questionnaire. Headache. 2001;41:854–861.
    1. Pryse-Phillips W. Evaluating migraine disability:the headache impact test instrument in context. Can J Neurol Sci. 2002;29(Suppl 2):S11–S15.
    1. Steiner TJ, Lipton RB. Lifting the burden: the global campaign against headache (2018) the headache-attributed lost time (HALT) indices: measures of burden for clinical management and population-based research. J Headache Pain. 2018;19:12.
    1. 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;20:6.
    1. Torres-Ferrus M, Alpuente A, Pozo-Rosich P. How much do calcitonin gene-related peptide monoclonal antibodies improve the quality of life in migraine? A patient’s perspective. Curr Opin Neurol. 2019;32:395–404.
    1. Viana M, Genazzani AA, Terrazzino S, Nappi G, Goadsby PJ. Triptan nonresponders: do they exist and who are they? Cephalalgia. 2013;33:891–896.
    1. American Headache Society The American headache society position statement on integrating new migraine treatments into clinical practice. Headache. 2019;59:1–18.
    1. Evers S, Afra J, Frese A, Goadsby PJ, Linde M, May A, Sándor PS, European Federation of Neurological Societies EFNS guideline on the drug treatment of migraine--revised report of an EFNS task force. Eur J Neurol. 2009;16:968–981.
    1. D’Amico D, Leone M, Grazzi L, Bussone G. When should “chronic migraine” patients be considered “refractory” to pharmacological to pharmacological prophylaxis? Neurol Sci. 2008;29:S55–S58.
    1. Ornello R, Casalena A, Frattale I, Gabriele A, Affaitati G, Giamberardino MA, Assetta M, Maddestra M, Marzoli M, Viola S, Cerone D, Marini C, Pistoia F, Sacco S. Real-life data on the efficacy and safety of erenumab in the Abruzzo region, Central Italy. J Headache Pain. 2020;21:32.
    1. Mitsikostas DD, Mantonakis LI, Chalarakis NG. Nocebo is the enemy, not placebo: a meta-analysis of reported side effects after placebo treatment in headaches. Cephalalgia. 2011;31:550–561.
    1. Mitsikostas DD. Nocebo in headaches: implications for clinical practice and trial design. Curr Neurol Neurosci Rep. 2012;12:132–137.
    1. Krymchantowski AV, Bigal ME. Polytherapy in the preventive and acute treatment of migraine: fundamentals for changing the approach. Expert Rev Neurother. 2006;6:283–289.
    1. Krymchantowski AV, da Cunha JC, Bigal ME. Topiramate plus nortriptyline in the preventive treatment of migraine: a controlled study for nonresponders. J Headache Pain. 2012;13:53–59.
    1. Pascual J, Leira R, Láinez J. Combined therapy for migraine prevention? Clinical experience with a beta-blocker plus sodium valproate in 52 resistant migraine patients. Cephalalgia. 2003;23:961–962.
    1. Pascual J, Rivas M, Leira R. Testing the combination beta-blocker plus topiramate in refractory migraine. Acta Neurol Scand. 2007;115:81–83.
    1. Scher AI, Rizzoli PB, Loder EW. Medication overuse headache: an entrenched idea in need of scrutiny. Neurology. 2017;89:1296–1304.
    1. Fritsche G, Eberl A, Katsarava Z, Limmroth V, Diener HC. Drug-induced headache: long-term follow-up of withdrawal therapy and persistence of drug misuse. Eur Neurol. 2001;45:229–235.
    1. Holm JE, Lokken C, Myers TC. Migraine and stress: a daily examination of temporal relationships in women migraineurs. Headache. 1997;37:553–558.
    1. Fernández-de-Las-Peñas C, Fernández-Muñoz JJ, Palacios-Ceña M, Parás-Bravo P, Cigarán-Méndez M, Navarro-Pardo E. Sleep disturbances in tension-type headache and migraine. Ther Adv Neurol Disord. 2017;11:1756285617745444.
    1. Freedom T, Evans RW. Headache and sleep. Headache. 2013;53:1358–1366.
    1. Lateef T, Witonsky K, He J, Ries Merikangas K. Headaches and sleep problems in US adolescents: findings from the National Comorbidity Survey - adolescent supplement (NCS-A) Cephalalgia. 2019;39:1226–1235.
    1. Ripa P, Ornello R, Degan D, Tiseo C, Stewart J, Pistoia F, Carolei A, Sacco S. Migraine in menopausal women: a systematic review. Int J Women's Health. 2015;7:773–782.
    1. Sacco S, Merki-Feld GS, Ægidius KL, Bitzer J, Canonico M, Kurth T, Lamp C, Lidegaard O, MacGregor A, Maassen VanDenBrink A, Mitsikostas D, Nappi RE, Ntaios G, Sandset PM, Martelletti P, on behalf of the European Headache Federation (EHF) and the European Society of Contraception and Reproductive Health (ESC) Hormonal contraceptives and risk of ischemic stroke in women with migraine: a consensus statement from the European headache federation (EHF) and the European Society of Contraception and Reproductive Health (ESC) J Headache Pain. 2017;18:108.
    1. Sacco S, Ægidius KL, Bitzer J, Canonico M, Gantenbein AR, Kurth T, Lampl C, Lidegaard Ø, MacGregor AE, MaassenVanDenBrink A, Merki-Feld GS, Mitsikostas DD, Nappi RE, Ntaios G, Paemeleire K, Sandset PM, Terwindt G, Vetvik KG, Martelletti P. Use of estrogens and progestogens in women of reproductive age and their effect on migraine: a consensus statement from the European headache federation (EHF) and the European Society of Contraception and Reproductive Health (ESCRH) J Headache and Pain. 2018;19:76.
    1. Sacco S, Olivieri L, Bastianello S, Carolei A. Comorbid neuropathologies in migraine. J Headache Pain. 2006;7:222–230.
    1. Sacco S, Cerone D, Carolei A. Comorbid neuropathologies in migraine: an update on cerebrovascular and cardiovascular aspects. J Headache Pain. 2008;9:237–248.
    1. Sacco S, Ricci S, Carolei A. Migraine and vascular diseases: potential implications for management. Cephalalgia. 2012;32:785–795.
    1. Sacco S, Kurth T. Migraine and the risk of stroke and cardiovascular disease. Curr Cardiol Rep. 2014;16:524.
    1. Sacco S, Pistoia F, Degan D, Carolei A. Conventional vascular risk factors: their role in the association between migraine and cardiovascular diseases. Cephalalgia. 2015;35:146–164.
    1. Gelaye B, Sacco S, Brown WJ, Nitchie H, Ornello R, Peterlin BL. Body composition status and the risk of migraine: a meta-analysis. Neurology. 2017;88:1795–1804.
    1. Ornello R, Ripa P, Pistoia F, Degan D, Tiseo C, Carolei A, Sacco S. Migraine and body mass index categories: a systematic review and meta-analysis of observational studies. J Headache Pain. 2015;16:27.
    1. Mitsikostas DD, Ashina M, Craven A, Diener HC, Goadsby PJ, Ferrari MD, Lampl C, Paemeleire K, Pascual J, Siva A, Olesen J, Osipova V, Martelletti P, EHF committee European headache federation consensus on technical investigation for primary headache disorders. J Headache Pain. 2015;17:5.
    1. Hoffmann J, Mollan SP, Paemeleire K, Lampl C, Jensen RH, Sinclair AJ. European headache federation guideline on idiopathic intracranial hypertension. J Headache Pain. 2018;19:93.
    1. Serrano D, Lipton RB, Scher AI, Reed ML, Stewart WBF, Adams AM, Buse DC. Fluctuations in episodic and chronic migraine status over the course of 1 year: implications for diagnosis, treatment and clinical trial design. J Headache Pain. 2017;18:101.
    1. Diener HC, Goadsby PJ, Ashina M, Al-Karagholi MA, Sinclair A, Mitsikostas D, Magis D, Pozo-Rosich P, Irimia Sieira P, Làinez MJ, Gaul C, Silver N, Hoffmann J, Marin J, Liebler E, Ferrari MD. Non-invasive vagus nerve stimulation (nVNS) for the preventive treatment of episodic migraine: the multicentre, double-blind, randomised, sham-controlled PREMIUM trial. Cephalalgia. 2019;39:1475–1487.
    1. Pistoia F, Sacco S, Carolei A. Behavioral therapy for chronic migraine. Curr Pain Headache Rep. 2013;17:304.
    1. Steiner TJ, Jensen R, Katsarava Z, Linde M, MacGregor EA, Osipova V, Paemeleire K, Olesen J, Peters M, Martelletti P. Aids to management of headache disorders in primary care (2nd edition) : on behalf of the European Headache Federation and Lifting The Burden: the Global Campaign against Headache. J Headache Pain. 2019;20:57.
    1. Becker WJ, Christie SN, Mackie G, Cooper P; Canadian Headache Society Migraine Strategy Task Force Consensus statement: the development of a national Canadian migraine strategy. Can J Neurol Sci. 2010;37:449–456.
    1. Steiner TJ, Antonaci F, Jensen R, Lainez MJA, Lanteri-Minet M, Valade D. Recommendations for headache service organisation and delivery in Europe. J Headache Pain. 2011;12:419–426.
    1. Marmura MJ, Hou A. Inpatient Management of Migraine. Neurol Clin. 2019;37:771–788.
    1. Bloudek LM, Stokes M, Buse DC, Wilcox TK, Lipton RB, Goadsby PJ, Varon SF, Blumenfeld AM, Katsarava Z, Pascual J, Lanteri-Minet M, Cortelli P, Martelletti P. Cost of healthcare for patients with migraine in five European countries: results from the international burden of migraine study (IBMS) J Headache Pain. 2012;13:361–378.
    1. Negro A, Sciattella P, Rossi D, Guglielmetti M, Martelletti P, Mennini FS. Cost of chronic and episodic migraine patients in continuous treatment for two years in a tertiary level headache Centre. J Headache Pain. 2019;20:120.
    1. Young WB, Park JE, Tian IX, Kempner J. The stigma of migraine. PLoS One. 2013;8:e54074.
    1. Sabariego C, Coenen M, Ito E, Fheodoroff K, Scaratti C, Leonardi M, Vlachou A, Stavroussi P, Brecelj V, Kovačič DS, Esteban E. Effectiveness of integration and re-integration into work strategies for persons with chronic conditions: a systematic review of European strategies. Int J Environ Res Public Health. 2018;15:552.

Source: PubMed

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot

3
Tilaa