Belvís et al. The Journal of Headache and Pain (2021) 22:74 https://doi.org/10.1186/s10194-021-01267-x The Journal of Headache and Pain RESEARCH ARTICLE Open Access MAB-MIG: registry of the spanish neurological society of erenumab for migraine prevention Robert Belvís1*, Pablo Irimia2, Patricia Pozo-Rosich3,4, Carmen González-Oria5, Antonio Cano6, Javier Viguera7, Belén Sánchez8, Francisco Molina9, Isabel Beltrán10, Agustín Oterino11, Elisa Cuadrado12, Angel Gómez-Camello13, Miguel Alberte-Woodward14, Carmen Jurado15, Teresa Oms16, David Ezpeleta17, Javier Díaz de Terán18, Noemí Morollón1,19, Germán Latorre20, Marta Torres-Ferrús3,4, Alicia Alpuente3,4, Raquel Lamas5, Carlos Toledano2, Rogelio Leira21, Sonia Santos22 and Margarita Sánchez del Río23 Abstract Background: Erenumab was approved in Europe for migraine prevention in patients with ≥ 4 monthly migraine days (MMDs). In Spain, Novartis started a personalized managed access program, which allowed free access to erenumab before official reimbursement. The Spanish Neurological Society started a prospective registry to evaluate real-world effectiveness and tolerability, and all Spanish headache experts were invited to participate. We present their first results. Methods: Patients fulfilled the ICHD-3 criteria for migraine and had ≥ 4 MMDs. Sociodemographic and clinical data were registered as well as MMDs, monthly headache days, MHDs, prior and concomitant preventive treatment, medication overuse headache (MOH), migraine evolution, adverse events, and patient-reported outcomes (PROs): headache impact test (HIT-6), migraine disability assessment questionnaire (MIDAS), and patient global improvement change (PGIC). A > 50% reduction of MMDs after 12 weeks was considered as a response. Results: We included 210 patients (female 86.7%, mean age 46.4 years old) from 22 Spanish hospitals from February 2019 to June 2020. Most patients (89.5%) suffered from chronic migraine with a mean evolution of 8.6 years. MOH was present in 70% of patients, and 17.1% had migraine with aura. Patients had failed a mean of 7.8 preventive treatments at baseline (botulinum toxin type A—BoNT/A—had been used by 95.2% of patients). Most patients (67.6%) started with erenumab 70 mg. Sixty-one percent of patients were also simultaneously taking oral preventive drugs and 27.6% were getting simultaneous BoNT/A. Responder rate was 37.1% and the mean reduction of MMDs and MHDs was -6.28 and -8.6, respectively. Changes in PROs were: MIDAS: -35 points, HIT-6: -11.6 points, PIGC: 4.7 points. Predictors of good response were prior HIT-6 score < 80 points (p = 0.01), ≤ 5 prior preventive treatment failures (p = 0.026), absence of MOH (p = 0.039), and simultaneous BoNT/A treatment (p < 0.001). Twenty percent of patients had an adverse event, but only two of them were severe (0.9%), which led to treatment discontinuation. Mild constipation was the most frequent adverse event (8.1%). * Correspondence: rbelvis@santpau.cat 1 Headache and Neuralgia Unit, Department of Neurology, Hospital de La Santa Creu I Sant Pau, C/ Mas Casanova 90, CP08025 Barcelona, Spain Full list of author information is available at the end of the article © The Author(s). 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Belvís et al. The Journal of Headache and Pain (2021) 22:74 Page 2 of 8 Conclusions: In real-life, in a personalized managed access program, erenumab shows a good effectiveness profile and an excellent tolerability in migraine prevention in our cohort of refractory patients. Keywords: Erenumab, Migraine, Monoclonal antibody, Preventive treatment, Registry Background neurologists to treat patients before the official reim- Migraine is the second leading neurological cause of dis- bursement in January 2019. In the same date, the Head- ability and the first among young women according to ache Study Group of the Spanish Neurological Society the GBD2019 [1]; and approximately 38% of migraine (GECSEN) started MAB-MIG. This is a prospective, in- patients [2] need a preventive treatment to reduce this dependent, and multicentre registry of migraine patients disability. In Spain, several first line preventive drugs for treated with CGRP mAbs promoted by GECSEN, created episodic migraine (EM) are available: topiramate, sodium to evaluate their real-world effectiveness and tolerability valproate, amitriptyline, flunarizine and beta-blockers, by inviting headache specialists around the country. but only botulinum toxin type A (BoNT/A) and topira- Here, we present the data of effectiveness and tolerability mate are available for chronic migraine (CM) [3]. of the first 210 included migraine Spanish patients after The number of monthly migraine days (MMDs) after 12 weeks treatment with erenumab. 12 weeks of treatment is the main variable of efficacy for a preventive drug in migraine [4], despite the known de- Methods crease in prevention adherence beyond 12 weeks [5–7]. The MAB-MIG scientific committee is constituted by The loss of effectiveness and side effects account for this the members of GECSEN board (R. Belvís, S. Santos, G. progressive reduction in adherence. For these reasons, Latorre and C. Gonzalez-Oria) plus two independent ad- we urgently needed new preventive drugs, and anti- visors (P. Pozo-Rosich and R. Leira). This committee se- CGRP monoclonal antibodies (CGRP mAbs) have been lected the variables and advised on the design of the developed to cover these needs. database. It also resolved queries of the investigators and CGRP is a neuropeptide distributed throughout the assessed the final database and the statistical analyses. human body and highly concentrated in the trigemino- Each investigator acted according to their clinical cri- vascular system [8]. The levels of CGRP are increased teria, considering the European Medicines Agency and during the migraine attack in blood, tears, saliva, and the Spanish Neurology Society guidelines [3] that estab- cerebrospinal fluid, and normalized after the attack [9, lish the indication of erenumab from at least 4 MMDs. 10]. They are also permanently increased during CM The recommendations on erenumab treatment in mi- [11]. Moreover, the intravenous administration of CGRP graine, proposed by international experts [3, 40–42], causes migraine-like headaches in migraine patients and were made available to researchers. voluntaries [12]. Therefore, CGRP is an excellent target All patients included fulfilled the migraine criteria of for migraine therapy. the International Headache Society (IHS) [43]. Patients At present, there are three subcutaneous CGRP mAbs were between 18 and 65 years old, had ≥ 4 MMDs for marketed in Spain: erenumab (Aimovig®), galcanezumab the last three months and were treated with erenumab (Emgality®) and fremanezumab (Ajovy®). CGRP mAbs during a minimum 12-week period. Migraine started in block the CGRP receptor (erenumab) or the ligand itself their lives before age 50 and all of them had the migraine (galcanezumab and fremanezumab). Their phase II [13– diagnosis for a minimum of one year prior to inclusion 18] and phase III [19–33] trials against placebo have in the registry. Patients with recent cardiovascular or demonstrated the excellent safety and efficacy profile in cerebrovascular events (in the previous three months) migraine prevention [39]. Furthermore, several meta- were excluded. analyzes have supported these results [34–39]. The con- We collected the following variables: clusions that can be drawn from all these studies are that there appear to be no significant differences in safety be- 1. Demographical data: gender and age. tween each of the CGRPs, and that all of them are super- 2. Clinical data as migraine form (with/without aura), ior in efficacy to placebo. MMD and MHD (number of mean monthly Erenumab was the first CGRP mAb approved for mi- headache days). According to these definitions, we graine prevention in Europe. The European Medicines considered CM (≥ 15 MHDs) versus episodic Agency approval was communicated the 26th of July migraine-EM (< 15 MHDs). Moreover, the EM 2018 for patients with at least 4 MMDs for the last three group was subdivided into HFEM (10 to 14 MHDs) months. The Spanish Medicines Agency authorized a and low-frequency episodic migraine (LFEM; < 10 personalized managed access program that allowed MHDs). Belvís et al. The Journal of Headache and Pain (2021) 22:74 Page 3 of 8 3. Effectiveness variables. The following variables were least 12 weeks of erenumab treatment. The included collected at baseline and after 12-weeks treatment centres had a homogeneous geographic distribution with erenumab: number of MMDs and MHDs, and around the country. The mean age was 46.4 years-old patient-reported outcomes (PROs), including head- (18–65), and 86.7% of patients were women. ache impact test (HIT-6) score and the migraine The mean migraine duration was 26.5 years (3– disability assessment questionnaire (MIDAS) score. 25 years). Most patients (89.5%) had CM with an average Finally, patients implemented a patient global im- evolution of 8.6 years (3 months-25 years) and the pact changes (PGIC) scale to evaluate their remaining presented HFEM (10.5%). Seventy percent of satisfaction. patients presented MOH, and 17.1% fulfilled migraine with aura criteria. The average of MMDs was 17.1 days According to the IHS guidelines of controlled trials in (4–30), and of MHDs was 23.5 days. The mean MIDAS migraine [4], number of MMDs was considered the pri- score was 101.9 points, and the mean HIT-6 score was mary endpoint. Response was considered when a reduc- 68.8 points. tion in the number of migraine days > 50% was observed Patients had failed a mean of 7.8 (2–20) preventive between baseline and week 12 of treatment with treatments at baseline including BoNT/A. The later erenumab. had been used by 95.2% of patients. The most fre- Additionally, we collected other variables: prior pre- quently used oral preventive drugs were topiramate ventives drugs taken, including BoNT/A, previous over- (98.2%), amitriptyline (98.2%), flunarizine (94.7%) and use of acute medication, erenumab treatment alone or in beta-blockers (92.9%). combination with another preventive drug, initial erenu- The initial dose of erenumab was 70 mg in 67.6% of mab doses, and if there was a change in the erenumab patients and 140 mg in the remaining 32.4%. Regarding dosage after 12 weeks. Other changes measured were simultaneous preventive treatments, only 39.5% patients conversion from CM to EM, and medication overuse received exclusively erenumab as preventive treatment, headache (MOH). and in the remaining patients (60.5%) erenumab was added to another preventive drug that the patient already Tolerability analyses took. Thus, 27.6% of patients received BoNT/A plus ere- We collected all adverse events (AEs), and the MAB- numab, 12,2% topiramate plus erenumab and 49.1% a MIG scientific committee classified them as related or miscellanea of oral preventive drugs plus erenumab. non-related to erenumab treatment. According to Good Regarding effectiveness (Table 1), the responder rate Clinical Practice guidelines, we classified adverse events was 37.1%, and the mean reduction in MMDs was as mild, moderate, or severe, and we collected the drop- 6.5 days (from 17.1 to 11 days). MHDs were also reduced out rate. in 8.6 days (from 23.5 to 14.9 days). For statistical analysis we used the SPSS software (ver- After the 12-week period of treatment (Fig. 1), 28 sion 22.0; SPSS Inc., Chicago, IL, USA). Results were patients (13.3%) discontinued the treatment. The rea- expressed as means and standard deviations or as abso- sons were: 1) excellent effectiveness that allowed to lute number and percentages. Patient data were classified achieve the conversion to LFEM (20 patients; 9.5%), into two groups: baseline visit and 12-week visit. Com- 2) lack of effectiveness (4 patients; 1.9%), and 3) AEs parisons have been made using the Student's t-test for (4 patients; 1.9%). quantitative variables and contingency tables and the The remaining 182 patients (86.7%) continued with chi-square test for categorical variables. When the distri- erenumab treatment: with the same dose (44.7%), while bution of the data went out of normality, we used the 41,9% increased the dose thereafter (Fig. 1). After three Mann–Whitney U test. Statistical significance was con- months of follow-up, 14.8% continued to receive simul- sidered when p < 0.05. taneously BoNT/A and 50% were still under treatment Finally, MAB-MIG was classified as a low-intervention clinical trial by the Spanish Medicines Agency and was Table 1 Clinical responses and patient-reported outcomes approved by the Ethics Committee of Investigation with (PROs) at the baseline period and after week 12 of erenumab Medicines of the Health Area of Valladolid (PI 20–1790). treatment The name of the participant hospitals was anonymized Variable Baseline Week 12 Difference and the information regarding their patients was sent in MMDs 17.1 days 11.0 days -6.5 days encrypted form. MHDs 23.5 days 14.9 days -8.6 days HIT-6 score 68.8 points 57.2 points -11.6 points Results MIDAS score 101.9 points 66.9 points -35 points We included 210 patients from 22 Spanish hospitals, MOH 70% 43.4% -26.6% from February 2019 to June 2020, who had completed at Belvís et al. The Journal of Headache and Pain (2021) 22:74 Page 4 of 8 Fig. 1 Sector graph showing clustering of the 210 migraine patients according to erenumab response after 12 weeks of treatment with oral preventive drugs. We want remark that 69 pa- of MOH (p = 0.039). All the responder patients showed a tients (32.8%) continued erenumab despite of they HIT-6 score < 80 points making this index in a strong achieved to convert CM into HFEM. predictor factor of response at this cut point. Regarding PROs (Table 1): MIDAS score was reduced None of the erenumab doses, 70 or 140 mg, showed a 35 points (from 101.9 to 66.9), HIT-6 was reduced 11.6 better statistical power as predictor of good response points (from 68.8 to 57.2) and the mean PIGC assess- than the other (p = 0.647). However, the simultaneous ment was 4.7 points. BoNT/A treatment showed the strongest predictor We also tried to identify predictive response factors. In power of a good response (p < 0.001). On the contrary, this way we found a cut-off point in 5.9 previous preven- simultaneous oral preventives did not predict the re- tives failures (p = 0.026) (Table 2) above which only the sponse (p = 0.213). 10% of patients responded to erenumab treatment. Other In addition, the presence of aura showed a non- predictive factors were MIDAS score < 100 points (p = significant tendency as a predictor factor of good re- 0.006), < 80 points in HIT-6 score (p = 0.01), and absence sponse (p = 0.088). However, age (p = 0.557), gender (p = Table 2 Predictive factors of good response Variable Responders Non-responders p (n = 78) (n = 130) Age (years) 47.4 y 45.9 y 0.557 Gender (women) (n = 180) 65 (36.1%) 115 (63.9%) 0.294 Aura (n = 36) 18 (50%) 18 (50%) 0.088 CM (n = 186) 69 (37.1%) 117 (62.9%) 0.727 EM (n = 22) 9 (40.9%) 13 (59.1%) 0.907 MOH (n = 145) 61 (42.1%) 84 (57.9%) 0.039 Prior BoNT/A (n = 198) 74 (37.4%) 124 (62.6%) 0.867 Erenumab 70 mg (n = 140) 51 (36.4%) 89 (63.6%) 0.760 Erenumab 140 mg (n = 68) 27 (39.7%) 41 (60.3%) 0.648 Simultaneous BoNT/A (n = 57) 34 (59.6%) 23 (40.4%) < 0.001 Simultaneous oral preventives (n = 126) 43 (34.1%) 83 (65.9%) 0.213 Belvís et al. The Journal of Headache and Pain (2021) 22:74 Page 5 of 8 0.294), the form of migraine HFEM/CM (p = 0.727), and Discussion evolution of CM (p = 0.514) did not show any association We present the first multicentre and prospective real- to response. world experience of erenumab in the preventive treat- Finally, regarding tolerability, the percentage of AEs ment of migraine in Spain. Erenumab presents an excel- was 20%, but only four patients (1.9%), suffered severe lent tolerability profile in our registry, but a slightly adverse events leading to treatment discontinuation. lower effectiveness, response rate of 37%, comparing to Two patients had a skin rash attributed to the first ere- 39–50% that is the average of phase III clinical trials numab injection; the other two patients presented AEs [19–32], open-label extension studies [44–46], and meta- not related to erenumab: one patient, under paroxetine analysis [34–39]. treatment, presented a serotoninergic syndrome while This can be attributed to the fact that most of the 210 overusing zolmitriptan; and the other one was diagnosed patients included were highly refractory CM patients and of cutaneous melanoma, but the skin lesion existed pre- therefore would have been excluded from clinical trials viously to the erenumab treatment onset. [19–32]. For example, the LIBERTY trial [23] analysed Specifically, forty-two patients presented 57 AEs, being erenumab versus placebo in 246 patients with EM who constipation the most frequent (7.6%). No patients were unsuccessfully treated (in terms of efficacy or toler- needed treatment or consultation by this AEs. Table 3 ability, or both) with 2–4 preventive treatments. The ere- details AEs reported by patients after 12 weeks of treat- numab response rate reported was 50% [23]. Our ment with erenumab. response rate is lower, but it must be considered that Finally, we did not find any predictive factor of AEs, our patients were more refractory (they failed an average but the dose of 140 mg showed a non-significant ten- of 7 previous preventives), the majority had CM and part dency to present more AEs than the dose of 70 mg of the study was carried out during the most serious (p = 0.069). phase of the COVID-pandemic. Another explanation could be that the more frequent erenumab initial dose prescribed was 70 mg because ini- tial dose was a discretionary decision of the investigator. Table 3 Adverse events (AEs) collected during the 12 weeks of Since patients included in our study have a long history erenumab therapy of migraine, a high number of MMDs, numerous failures AE Absolute number and percentage to preventive migraine drugs and high impact in HIT-6 Constipation 16 (7.6%) and MIDAS scales compared with patients from clinical Flu-like symptoms 8 (3.8%) trials, perhaps effectiveness could have been better if all the investigators had started the treatment with the Pruritus after injection 6 (2.8%) 140 mg dose. Fatigue 5 (2.3%) As expected, the lower the scores in the HIT-6 and Dizziness 3 (1.4%) MIDAS scales, and the fewer the number of preventive Nausea after injection 3 (1.4%) drugs that have previously failed, the more likely the ere- Upper respiratory tract infection 2 (0.9%) numab treatment will be effective. These are the effect- Skin rash after injection 2 (0.9%) iveness predictors that we have found in our study, together with the absence of MOH. Nevertheless, one Lymphadenopathy 1 (0.4%) unexpected predictive factor in our study was the simul- Serotoninergic syndrome 1 (0.4%) taneous treatment with erenumab plus BoNT/A. This as- Loss of sexual desire 1 (0.4%) sociation was the strongest predictive factor of a good Melanoma 1 (0.4%) response and showed an excellent tolerability profile. Diarrhoea 1 (0.4%) A huge number of real-world experiences analysing Myalgia 1 (0.4%) erenumab in migraine prevention are being published around the world [47–63]. These experiences already in- Injection site pain 1 (0.4%) clude more than 2,000 patients with migraine, and, Muscular spam 1 (0.4%) among them, we can find eleven one-centre studies Panic attack 1 (0.4%) (seven prospective [48, 53, 54, 56, 57, 59, 61] and four Palpitations 1 (0.4%) retrospectives [50–52, 62]) and five multicentre (four Dehydration 1 (0.4%) prospective [49, 55, 58, 60] and one retrospective [63]). Hypermenorrhoea 1 (0.4%) Our registry includes the second largest sample of mi- graine patients treated with erenumab in a multicentric Death 0 (0%) prospective registry. A published Italian study [55] in- Total 57 cluded more patients, 372 patients, but this initiative was Belvís et al. The Journal of Headache and Pain (2021) 22:74 Page 6 of 8 composed by a group of headache experts and it in- Likewise, a high number of failures with previous pre- cluded only ten Italian centres, and nine of them were ventive drugs, overuse of symptomatic medication and localized in the north of Italy. Our study is the official high degrees of disability are the main predictors of poor registry of the Spanish Neurological Society and includes response. On the other hand, the concomitant use of 22 centres with homogeneous representation of the BoNT/A plus erenumab seems to present an excellent country. Moreover, the average number of prior prevent- tolerability profile, as it has already been proposed in ive drug failures was 3–5 in the Italian study [55] and su- several studies [65, 66] and is the strongest predictive perior to 7 in ours, which means that our patients are factor of good response. more complex and treatment-refractory than the patients Abbreviations of the Italian study. Despite these differences, both the BoNT/A: Botulinum toxin type A; CGRP: Calcitonin gene-related peptide; Italian study [55] and the other real-world experiences CM: Chronic migraine; EM: Episodic migraine; HFEM: High frequency episodic [47–63] conclude, like our registry, that erenumab is use- migraine; HIT-6: Headache impact test; ICHD: International Classification of Headache Disorders; IHS: International Headache Society; LFEM: Low ful in the prevention of EM and CM and presents a good frequency episodic migraine; mAbs: Monoclonal antibodies; MHD: Monthly tolerability profile. headache days; MIDAS: Migraine disability assessment questionnaire; Erenumab has shown scarce adverse events in our MMD: Monthly migraine days; MOH: Medication overuse headache; PGIC: Patient global improvement change; PROs: Patient-reported outcomes registry (20%), like in the phase II [13–18] and phase III [19–32] clinical trials, meta-analysis [34–39], open-label Acknowledgements extension studies [44–46] and real-world experiences We thank Ignasi Gich for the statistical advice to analyse MAB-MIG registry. We also want to thank the hospital´s outpatient pharmacy and nursing staff [46–62]. Most of the adverse events were mild and tran- for their participation and involvement in the therapy with CGRP mAbs. sient in our study. Mild constipation, flu-like symptoms, transient pruritus at the injection site and fatigue were Authors’ contributions the only adverse events with incidences superior to 2%. RB: Registry coordinator, Member of the Scientific Committee, Choice of variables and base design, Patient recruitment, Data management, Statistical We only collected two severe adverse events related to analysis, Redaction of the paper. PI. Patient recruitment, Redaction of the erenumab treatment (two skin rash after injection) that paper. PPR. Member of the Scientific Committee, Choice of variables and represent 0.9% of our patients, a similar figure to that of base design, Patient recruitment, Data management, Statistical analysis, Redaction of the paper. CGO. Member of the Scientific Committee, Choice of clinical trials and real-world experiences (1–3%) [19–39, variables and base design, Patient recruitment, Data management, Statistical 44–62]. analysis, Redaction of the paper. JV. Patient recruitment, Redaction of the Regarding the initial dose of erenumab, we have not paper. BS. Patient recruitment, Redaction of the paper. FM. Patient recruitment, Redaction of the paper. MSR. Patient recruitment, Redaction of found any difference on effectiveness between them, the paper. IB. Patient recruitment, Redaction of the paper. AO. Patient unlike other studies [64]. On the other hand, the ex- recruitment, Redaction of the paper. EC. Patient recruitment, Redaction of the cellent tolerability pattern of the two doses of erenu- paper. AGC. Patient recruitment, Redaction of the paper. MAW. Patient recruitment, Redaction of the paper. CJ. Patient recruitment, Redaction of the mab is already known and our study confirms it, paper. TO. Patient recruitment, Redaction of the paper. DE. Patient despite the 140 mg dose showing a non-significant recruitment, Redaction of the paper. JDT. Patient recruitment, Redaction of trend to be related to more adverse events than the the paper. NM. Patient recruitment, Redaction of the paper. GL. Member of the Scientific Committee, Patient recruitment, Redaction of the paper. MTF. dose of 70 mg. Patient recruitment, Redaction of the paper. AL. Patient recruitment, This first report of the results of the MAB-MIG regis- Redaction of the paper. RL. Patient recruitment, Redaction of the paper. CT. try has some limitations. First: patients included are the Patient recruitment, Redaction of the paper. RL. Member of the Scientific Committee, Choice of variables and base design, Patient recruitment, Data most refractory ones of Spanish headache units and they management, Statistical analysis, Redaction of the paper. SS. Registry were waiting the arrival of mAbs. For this reason, they coordinator, Member of the Scientific Committee, Choice of variables and do not exactly represent the Spanish real-world experi- base design, Patient recruitment, Data management, Statistical analysis, Redaction of the paper. The author(s) read and approved the final ence. Second: we present effectiveness and tolerability re- manuscript. sults at three months of therapy, a short follow-up. Finally, we have not analysed the comorbidities exist- Funding We declare that we have not received any scholarship, nor grant, nor help to ence. Despite these limitations, MAB-MIG results have do the MAB-MIG registry. great strength because they are the first post-marketing results of erenumab collected by a neurology scientific Availability of data and materials Generated data in the MAB-MIG registry are not publicly available due to the society in 22 hospitals in one European country. Spanish law for the protection of personal data but are available from the corresponding author on reasonable request. Conclusions Declarations Our registry supports the tolerability and effectiveness of erenumab in the real-world clinical setting. In this way, Ethics approval and consent to participate one out three highly refractory migraine patients MAB-MIG was classified as a low-intervention clinical trial by the Spanish Medicines Agency and Medical Devices and was approved by the Ethics responded to erenumab with almost no relevant side Committee of Investigation with Medicines of the Health Area of Valladolid, effects. Spain (PI 20–1790). Belvís et al. The Journal of Headache and Pain (2021) 22:74 Page 7 of 8 Consent for publication 12. Hansen JM, Hauge AW, Olesen J, Ashina M (2010) Calcitonin gene-related Authors consent the publication of the paper MAB-MIG: REGISTRY OF THE peptide triggers migraine-like attacks in patients with migraine with aura. SPANISH NEUROLOGICAL SOCIETY OF ERENUMAB FOR MIGRAINE PREVENTI Cephalalgia 30:1179–1186 ON. THREE-MONTHS RESULTS in The Journal of Headache and Pain. 13. Dodick DW, Goadsby PJ, Silberstein SD, Lipton RB, Olesen J, Ashina M (2014) Safety and efficacy of ALD403, an antibody to calcitonin gene-related peptide, for the prevention of frequent episodic migraine: a randomised, Competing interests double-blind, placebo-controlled, exploratory phase 2 trial. Lancet Neurol 13: Within the prior 24 months, RB, PI, PP-R, CG-O, and MSDR have received hon- 1100–1107 oraria as consultant and/or speaker for Eli-Lilly, Novartis, Teva, and Allergan/ 14. Dodick DW, Goadsby PJ, Spierings EL, Scherer JC, Sweeney SP, Grayzel Abbvie. DS (2014) Safety and efficacy of LY2951742, a monoclonal antibody to calcitonin gene-related peptide, for the prevention of migraine: a phase Author details 2, randomised, double-blind, placebo-controlled study. 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