Burden and attitude to resistant and refractory migraine: a survey from the European Headache Federation with the endorsement of the European Migraine & Headache Alliance

DOI: https://doi.org/10.1186/s10194- 021- 01252- 4

Abstract-Summary To overcome those issues, the European Headache Federation (EHF) issued a Consensus document to propose criteria to approach difficult-to-treat migraine patients in a standardized way.

The Consensus proposed well-defined criteria for resistant migraine (i.e., patients who do not respond to some treatment but who have residual therapeutic opportuni- ties) and refractory migraine (i.e., patients who still have debilitating migraine despite maximal treatment efforts).

The aim of this study was to better understand the perceived impact of resistant and refractory migraine and the attitude of physicians involved in migraine care toward those conditions.

A relevant proportion of participants reported that patients with resistant and refractory migraine were frequently seen in their clinical practice (49.5% for resis- tant and 28.9% for refractory migraine); percentages were higher when considering only those working in specialized headache centers (75% and 46% respectively).

Many physicians reported low or moderate confidence in managing resistant (8.1% and 43.3%, respectively) and refractory (20.7% and 48.4%, respectively) migraine patients; confidence in treating resistant and refractory migraine patients was different according to the level of care and to the number of patients visited per week.

Patients with resistant and refractory migraine were infrequently referred to more specialized centers (12% and 19%, respectively); also in this case, figures were different according to the level of care.

There is the need of more evidence regarding the management of those patients the organization of care and available

to

and clear guidance referring opportunities.

Extended: Underlying mechanisms in migraine are far from being entirely clear and there hope that the ongoing future research may shade light on novel targets which may allow the development of new drugs.

Background New migraine treatments, both acute and preventative, such as lasmiditan, mono- clonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway, and gepants are changing the landscape of migraine treatment offering new opportunities and challenges [173–177].

In details, the new definitions of the difficult to treat migraine included non-

response to acute and preventative medications.

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Further, patients who tried three different classes of migraine preventative and

still suffer eight debilitating migraine days classify for resistant migraine.

In order to be defined as refractory, failure to all available classes of migraine

preventatives, including mAbs targeting the CGRP pathway, is required.

Methods We conducted a web-questionnaire-based cross-sectional international study involv- ing headache physicians.

All physicians involved in the care of patients with headache, without any restric- tion referring to country of residency, specialization, and years of experience in headache care were entitled to fill the questionnaire.

Work settings categories were defined, according to EHF definitions of the level of care [178], as follows: (1) first level of care—General primary care defined as first-line headache service (accessible first contact for most people with headache); (2) second level of care - Special-interest headache care defined as ambulatory care delivered by physicians with a special interest in headache; (3) third level of care— Headache Specialists Centers defined as advanced multidisciplinary care delivered by headache specialists in hospital-based centers.

The questionnaire was not anonymous, and participants were requested to pro-

vide consent to be listed as contributors to the study.

Results Resistant migraine was frequently encountered in clinical practice.

137/277 (49.5%) participants reported that they manage very frequently patients with resistant migraine, 100 (36.1%) participants reported that they manage occa- sionally those patients, and 40 (14.4%) reported that they manage rarely those patients.

80/277 (28.9%) participants reported that they manage very frequently patients with refractory migraine, 110 (39.7%) reported that they manage occasionally those patients, and 86 (31.0%) reported that they manage rarely those patients.

245/277 (88.4%) respondents reported that patients with resistant migraine were treated in their own center, while 32 (11.6%) reported that patients were referred to a more specialized center.

Referring to the ideal setting of care, 22 (6%) respondents considered that resis- tant migraine should be managed in general primary care, 162 (43%) in special interest headache care, and 191 (51%) in specialized headache centers.

Discussion Resistant and refractory migraine are particularly common in tertiary level head- ache centers, where 75% and 46%, respectively, of the physicians use to see very frequently those patients.

Even in tertiary level headache centers, only 39% of physicians reported high

confidence in managing patients with refractory migraine.

Physicians with more experience (i.e., more patients visited per week and more years in practice) reported more often a high confidence in treating both resistant

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and refractory migraine, further highlighting the lack of standardized guidelines and the consequent physicians’ trend to mainly rely on their expertise.

We found a low referral to more advanced levels of care for patients with resis- tant and refractory migraine, despite a relevant proportion of physicians operating in the two more basic levels of care expressed from low to moderate confidence in treating those patients.

Conclusions Resistant and refractory migraine are conditions which are perceived as common in the clinical practice of those involved in the care of patients with migraine and working in dedicated headache care or centers.

It would be important to set up organized systems for referral of the difficult-to- treat patients from general primary care/neurology and eventually from special interest headache care to tertiary headache centers and to provide guidance on migraine care in situations where the positive clinical response if difficult to achieve. Further research is also needed to clarify the mechanisms which contribute to drug refractoriness in migraine, to understand the role of comorbidities and the therapeutic opportunities arising from combination drugs.

Acknowledgement A machine generated summary based on the work of Sacco, Simona; Lampl, Christian; Maassen van den Brink, Antoinette; Caponnetto, Valeria; Braschinsky, Mark; Ducros, Anne; Little, Patrick; Pozo-Rosich, Patricia; Reuter, Uwe; Ruiz de la Torre, Elena; Sanchez Del Rio, Margarita; Sinclair, Alexandra J.; Martelletti, Paolo; Katsarava, Zaza; 2021 in The Journal of Headache and Pain.

Burden of migraine among japanese patients: a cross-sectional National Health and Wellness Survey