Abstract
Introduction
Migraine has a worldwide 1-year prevalence of 15–18% with a female-to-male ratio of 3:1. 1 The prevalence is increased during the reproductive years, 2 often occurring in young women who desire to have children. Since 2018, three monoclonal antibodies (mABs) for the prophylaxis of migraine attacks (MAs) have been approved. Information on risks of these antibodies (erenumab, galcanezumab, and fremanezumab) during pregnancy and breastfeeding is, therefore, important, but, to date, scarce. Herein, we describe a breastfeeding mother with longstanding very active migraine and failure of established prophylactic medication who was treated with erenumab without any obvious adverse effects in her or her child.
Case Report
A 35-year-old woman suffered from migraine without aura since her 15th year of age with average 4 days of migraine per month and, during college, up to 6 days/month. MAs were treated using rizatriptan, subsequently zolmitriptan and sumatriptan. MAs lasted up to 72 hours, with heavy nausea and vomiting. Since 2008, number of days of migraine increased up to 10–15/month. Therefore, migraine prophylaxis was started with atenolol and subsequently was changed to valproic acid, flunarizin, topiramate, and nortriptyline. None of these drugs resulted in sufficient reduction of MAs, or had to be cancelled because of marked adverse effects.
In summer 2016, the patient became pregnant and experienced reduction of MAs to 5/month. Attacks were treated with sumatriptan. From the fifth month of pregnancy, no further MAs occurred. In May 2017, she delivered a healthy son (birth weight 3,425 g, body height 54 cm). She started breastfeeding immediately after delivery and added baby food after 6 months. During puerperium, MAs increased. Treatment with sumatriptan was instituted, but due to reduced efficacy, intravenous paracetamol and metoclopramide were necessary at various times. Until January 2019, the average MAs frequency was up to 15 migraine days/month. Moreover, she experienced migraine status in late January 2019 and was, therefore, treated with oral prednisolone, which resolved the headache quickly.
Because of this marked increase of migraine and despite the fact that the patient decided to continue breastfeeding, erenumab 70 mg was started in February 2019 after comprehensive information concerning potential risks and side effects. She breastfed her son twice a day on average. Treatment of erenumab led to a rapid reduction of MAs (MA frequency in February was 7 days, March it was 3 days, April it was 5 days, and May it was 7 days). The monthly consumption of sumatriptan could be reduced significantly, and its effect started earlier and lasted longer.
No adverse effects occurred. The son developed adequately, each of seven mandatory childhood check-ups was normal. In June 2019, his body weight was 12.5 kg and his height was 86.5 cm. No infections occurred, no problems with nutrition evolved. In summary, treatment with erenumab resulted in a pronounced improvement in the quality of life in the patient and no adverse effects occurred in her son despite her continued breastfeeding. Pharmacological data regarding erenumab concentrations in breast milk and in the child's blood were not obtained.
Discussion
Erenumab is a human IgG2 mAB (molecular weight: 146 kD) binding specifically to the extracellular domain of the calcitonin gene-related peptide receptor (CGRP-R). The mAB prevents its interaction with the neuropeptide CGRP that is involved in the pathophysiology of migraine. CGRP blood levels are elevated during MAs. 1 IgG molecules can pass into breast milk (colostrum) only during the first 2 weeks postpartum. Later permeation is impossible because of molecular size (>140 kD) and the fact that the pores between epithelial cells of the mammae close up to day 14 after birth. 3 Moreover, small amounts of mABs will be destroyed in the gastrointestinal (GI) tract of the child 4 and, additionally, large molecules are not able to permeate the GI tract after the first days of life.
There are several barriers minimizing the potential transfer of mABs into the infant through breastfeeding. 3 Low amounts of mABs have been only rarely detected in breast milk5,6 at a level that was unlikely to put breastfed children at risk. Therefore, several expert guidelines for treatment of rheumatoid arthritis and inflammatory bowel disease accept treatment with disease-related mABs during breastfeeding.7,8 To our knowledge until now, no adverse reactions from mABs after breastfeeding have been reported. Nevertheless, treatment with erenumab during breastfeeding should be used cautiously until more data are available.
Disclosure Statement
No competing financial interests exist.