Marja-Liisa Sumelahti MD, PhD, Specialist in Neurology, Faculty of Medicine and Health Technology, Tampere University, Finland. 
Sweden, Denmark, Norway and Finland have independently developed their regulations for reimbursing treatment with anti-CGRP monoclonal antibodies, resulting in different levels of access to treatment and inconsistent eligibility criteria.

Lars Jacob Stovner MD, PhD, Professor of Neurology, Norwegian University of Science and Technology and Norwegian Advisory Unit on Headaches, St. Olavs Hospital, Trondheim, Norway. 
Sweden, Denmark, Norway and Finland have independently developed their regulations for reimbursing treatment with anti-CGRP monoclonal antibodies, resulting in different levels of access to treatment and inconsistent eligibility criteria.

Lars Bendtsen MD, PhD, Associate Professor, Danish Headache Center, Department of Neurology, Rigshospitalet, Glostrup, University of Copenhagen, Denmark. 
Sweden, Denmark, Norway and Finland have independently developed their regulations for reimbursing treatment with anti-CGRP monoclonal antibodies, resulting in different levels of access to treatment and inconsistent eligibility criteria.

Signe Bruun Munksgaar‪d‬. 
The European Academy of Neurology guideline on the management of medication overuse headache (MOH) updates the 2011 guideline from the European Federation of Neurological Societies with new research and new diagnostic criteria.

Reference;

1. Eur J Neurol. 2020 Jul;27(7):1102-1116. doi: 10.1111/ene.14268. Epub 2020 May 19

Louise Ninett Carlse‪n‬. 
Three strategies are effective in reducing headache days in patients with MOH. These were compared in a non-blinded randomized trial in 120 patients with MOH associated with migraine or tensiontype headache: withdrawal plus preventive therapy from the outset,  preventive therapy alone with no advice on withdrawal, and withdrawal alone (with an option to start preventive therapy after two months).6

References: 

1. Hagen K, Albretsen C, Vilming ST, et al. Management of medication overuse headache: 1-year randomized multicentre open-label trial. Cephalalgia. 2009;29:221-32.
2. Silberstein SD, Blumenfeld AM, Cady RK, et al. Onabotulinum toxin A for treatment of chronic migraine: PREEMPT 24-week pooled subgroup analysis of patients who had acute headache medication overuse at baseline. J Neurol Sci. 2013;331:48-56.
3. Tepper SJ, Diener HC, Ashina M, et al. Erenumab in chronic migraine with medication overuse: Subgroup analysis of a randomized trial. Neurology. 2019;92):e2309-e2320.
4. Tassorelli C, Jensen R, Allena M, et al; the COMOESTAS Consortium. A consensus protocol for the management of medication-overuse headache: Evaluation in a multicentric, multinational study. Cephalalgia. 2014;34:645-655.
5. Pijpers JA, Kies DA, Louter MA, et al. Acute withdrawal and botulinum toxin A in chronic migraine with medication overuse: a double-blind randomized controlled trial. Brain. 2019;142:1203-1214.
6. Carlsen LN, Munksgaard SB, Nielsen M, et al. Comparison of 3 treatment strategies for medication overuse headache: a randomized clinical trial. JAMA Neurol. 2020;77:1069-1078.

Gürdal Sahin, MD, PhD, Specialist in Neurology and Head of the Skåneuro Private Headache and Movement Disorders Clinic, Institution for Clinical Sciences, Lund University. 
Social distancing during the Covid pandemic has limited clinicians’ ability to provide face-to-face care and disrupted the assessment, monitoring and supervision normally provided in outpatient clinics. Telemedicine is an option for providing care remotely that offers service continuity, with some success in the management of headache.1-3 Its uptake during the pandemic may foretell a wider role in the future (Figure 1).

References

1. Friedman DI, Rajan B, Seidmann A. A randomized trial of telemedicine for migraine management. Cephalalgia. 2019;39:1577-1585.
2. Müller KI, Alstadhaug KB, Bekkelund SI. Acceptability, feasibility, and cost of telemedicine for nonacute headaches: a randomized study comparing video and traditional consultations. J Med Internet Res. 2016;18:e140. doi: 10.2196/jmir.5221.
3. Müller KI, Alstadhaug KB, Bekkelund SI. Telemedicine in the management of non-acute headaches: a prospective, open-labelled non-inferiority, randomised clinical trial. Cephalalgia. 2017;37:855-863.
4. Landsness EC, Wang LH, Bucelli RC. Ziprasidone as a potential abortive therapy for status migrainosus. Neurohospitalist. 2016;6:151-156.
5. Dodick DW. CGRP ligand and receptor monoclonal antibodies for migraine prevention: evidence review and clinical implications. Cephalalgia. 2019;39:445-458.
6. Robblee J, Starling AJ, Halker Singh RB et al. Teleneurology for primary headache disorders. Practical Neurology 2020;June:31-9.

Ingela Nilsson Remahl MD, PhD, Head of the Headache Center, Karolinska University Hospital. 
Sweden, Denmark, Norway and Finland have independently developed their regulations for reimbursing treatment with anti-CGRP monoclonal antibodies, resulting in different levels of access to treatment and inconsistent eligibility criteria.

Marja-Liisa Sumelahti, MD, PhD, Specialist in Neurology, Faculty of Medicine and Health Technology, Tampere University, Finland. 
There has been concern during the Covid pandemic that the immunosuppressive effects of medicines may increase the risk of infection. Little is known about the effect of migraine preventive medication on immune function but laboratory evidence of immunosuppression has not been reflected in clinical practice. Despite theoretical concerns, CGRP antagonists may confer some degree of protection against the complications of Covid.

References

1. Sumelahti ML, Sumanen M, Sumanen MS, et al. My Migraine Voice survey: disease impact on healthcare resource utilization, personal and working life in Finland. J Headache Pain. 2020;21:118. doi: 10.1186/ s10194-020-01185-4.
2. Zaccara G, Giovannelli F, Giorgi FS, et al. Do antiepileptic drugs increase the risk of infectious diseases? A meta-analysis of placebo-controlled studies. Br J Clin Pharmacol. 2017;83:1873-1879.
3. Maier IL, Karch A, Mikolajczyk R, et al. Effect of betablocker therapy on the risk of infections and death after acute stroke—a historical cohort study. PLoS One. 2015 Feb 2;10(2):e0116836. doi: 10.1371/ journal.pone.0116836.
4. Szałach ŁP, Lisowska KA, Cubała WJ. The influence of antidepressants on the immune system. Arch Immunol Ther Exp (Warsz). 2019;67:143-151.
5. Ahmed F, Gaul C, García-Moncó JC, et al; REPOSE Principal Investigators. An open-label prospective study of the real-life use of onabotulinumtoxinA for the treatment of chronic migraine: the REPOSE study. J Headache Pain. 2019;20:26. doi: 10.1186/ s10194-019-0976-1.
6. Hess DC, Eldahshan W, Rutkowski E. COVID-19-related stroke. Transl Stroke Res. 2020;11:322-325.
7. American College of Cardiology, American Heart Association, Heart Failure Society of America. HFSA/ ACC/AHA Statement Addresses Concerns Re: Using RAAS Antagonists in COVID-19, https://www.acc.org/latest-in-cardiology/articles/2020/03/17/08/59/hfsaacc-aha-statement-addresses-concerns-re-using-raasantagonists-in-covid-19; accessed December 2020.
8. Skaria T, Mitchell KJ, Vogel O, et al. Blood pressure normalization-independent cardioprotective effects of endogenous, physical activity-induced αCGRP (α Calcitonin Gene-Related Peptide) in chronically hypertensive mice. Circ Res. 2019;125:1124-1140.
9. Mulder IA, Li M, de Vries T, et al. Anti-migraine calcitonin gene-related peptide receptor antagonists worsen cerebral ischemic outcome in mice. Ann Neurol. 2020;88:771-784.
10. Biohaven Pharmaceuticals. Biohaven Receives FDA May Proceed Letter to Begin Phase 2 Trial of Intranasal Vazegepant to Treat Lung Inflammation After COVID-19 Infection. 9 April 2020. https://www.biohavenpharma.com/investors/news-events/pressreleases/ 04-09-2020.; accessed December 2020.
11. Han L, Liu Y, Xiong H, et al. CGRP monoclonal antibody for preventive treatment of chronic migraine: an update of meta-analysis. Brain Behav. 2019;9:e01215. doi: 10.1002/brb3.1215.
12. Dodick DW. CGRP ligand and receptor monoclonal antibodies for migraine prevention: Evidence review and clinical implications. Cephalalgia. 2019;39:445-458.
13. Levin M, Silberstein SD, Gilbert R, et al. Basic considerations for the use of monoclonal antibodies in migraine. Headache. 2018;58:1689-1696.

Mattias Linde, MD, PhD, Professor of Neurology, Norwegian Advisory Unit for Headaches and NTNU Consultant Neurologist, Tjörn Headache Clinic. 
The group of people most highly burdened by migraine are women of childbearing age, with about 1 in 5 of 30- to 39-year-olds affected.1 The challenge of treatment and prevention during pregnancy and while breast feeding is therefore a frequent one. Fortunately, the frequency of migraine attacks declines towards the time of delivery; however, there is often a marked increase during the puerperium.2

References

1. Linde M, Stovner LJ, Zwart JA, et al. Time trends in the prevalence of headache disorders. The Nord-Trondelag Health Studies (HUNT 2 and HUNT 3). Cephalalgia. 2011;31:585-96.
2. Kvisvik EV, Stovner LJ, Helde G, et al. Headache and migraine during pregnancy and puerperium: the MIGRA-study. J Headache Pain. 2011;12:443-51.
3. Steiner TJ, Jensen R, Katsarava Z, et al. 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. doi: 10.1186/s10194-018-0899-2.
4. Varkey E, Cider A, Carlsson J, et al. Exercise as migraine prophylaxis: a randomized study using relaxation and topiramate as controls. Cephalalgia. 2011;31:1428-38.
5. Varkey E, Hagen K, Zwart JA, et al. Physical activity and headache: results from the Nord-Trøndelag Health Study (HUNT). Cephalalgia. 2008;28:1292-7.

Eili Tranheim Kase, PhD, Associate Professor, Department of Pharmacy, University of Oslo. 
Anti-CGRP monoclonal antibodies probably cross the placenta but there is no evidence of harm in humans as a result; levels in breast milk are very low, especially after one week. There are no data on human exposure to gepants during pregnancy but animal studies at doses comparable with clinical doses suggest any risk is low.

References

1. Pham-Huy A, Sadarangani M, Huang V, et al. From mother to baby: antenatal exposure to monoclonal antibody biologics. Expert Rev Clin Immunol. 2019;15:221-229.
2. Gisbert JP, Chaparro M. Safety of new biologics (vedolizumab and ustekinumab) and small molecules (tofacitinib) during pregnancy: a review. Drugs. 2020l;80:1085-1100.
3. Bussiere JL, Davies R, Dean C, et al. Nonclinical safety evaluation of erenumab, a CGRP receptor inhibitor for the prevention of migraine. Regul Toxicol Pharmacol. 2019;106:224-238.
4. Cohen-Barak O, Weiss S, Rasamoelisolo M, et al. A phase 1 study to assess the pharmacokinetics, safety, and tolerability of fremanezumab doses (225 mg, 675 mg and 900 mg) in Japanese and Caucasian healthy subjects. Cephalalgia. 2018;38:1960-1971.
5. Do TP, Guo S, Ashina M. Therapeutic novelties in migraine: new drugs, new hope? J Headache Pain. 2019;20:37. doi: 10.1186/s10194-019-0974-3.
6. de Vries T, Villalón CM, MaassenVanDenBrink A. Pharmacological treatment of migraine: CGRP and 5-HT beyond the triptans. Pharmacol Ther. 2020;211:107528. doi: 10.1016/j. pharmthera.2020.107528.
7. Palmeira P, Quinello C, Silveira-Lessa AL, et al. IgG placental transfer in healthy and pathological pregnancies. Clin Dev Immunol. 2012;2012:985646. doi: 10.1155/2012/985646.