LAUSR

Dear Editor, Migraine is very common in women of childbearing age, reaching a prevalence of 25% [1]. The preventive treatment of migraine in women of reproductive age must be carefully chosen, since some oral drugs like valproate and topiramate have known teratogenic effects. The new anti-calcitonin Gene-Related Peptide (CGRP) monoclonal antibodies represent a new era in the preventive treatment of migraine, because of their favorable efficacy and tolerability profile. However, there are very limited data on their effects during pregnancy; therefore—since CGRP is a potent vasodilator potentially involved in the blood flow regulation in the uteroplacental system—theoretical concerns exist [2]. Erenumab—a fully human monoclonal antibody targeting the receptor of the CGRP and the first drug in this new class— showed to be effective and well tolerated in episodic and chronic migraine [3]. In a preand post-natal development study in cynomolgus monkey, erenumab administration from gestation days 20–22 through birth induced no adverse effects on the pregnancy and the embryo-fetal growth and development at exposures 17-fold the human dose of 140 mg/month [4]. Nevertheless, due to the lack of clinical data and the theoretical role of CGRP in regulating uterine vascular resistance, the use of erenumab during pregnancy is currently not recommended. We would like to share with you our experience of the first case of the occurrence of pregnancy during erenumab treatment in a patient affected by chronic migraine. Written informed consent was obtained from the patient for the description and publication of this case report. This is a 37-year-old woman,married, working as a lawyer. Her medical history was positive for endometriosis, polycystic ovarian and an untreated anxiety disorder. She had no previous pregnancy or abortions. The patient was affected by migraine without aura since the age of 6. Until early adolescence, migraine had a frequency of 4 days per month and was responsive to non-steroidal anti-inflammatory drugs. Migraine started worsening at the age of 16, becoming chronic (15– 20 days/month) without medication overuse. The putative chronification factors were stress and anxiety. The attacks were successfully treated with triptans. Over the course of the disease, the patient used amitriptyline, cinnarizine, flunarizine, propranolol, metoprolol, and topiramate, but all these treatments proved ineffective or had unbearable side effects, which led to a premature discontinuation. At the time of her first visit to our unit, she was on prophylaxis with sodium valproate 600 mg/day, showing a migraine frequency of 18 days per month. General and neurological examination, brain MRI scan, and blood tests were unremarkable. On 4/4/ 2019 the patient discontinued valproate due to its low efficacy and to weight gain, and started erenumab 70 mg subcutaneously every 28 days. Subsequently she was checked at our unit on a monthly basis. Erenumab was rapidly effective, reducing the frequency of migraine to 7 days per month since its first administration. On 8/8/2019, at the follow-up visit scheduled for the fifth erenumab administration, the patient informed us of her pregnancy, documented on 7/8/2019 by positive deep stick urine test and high beta-HGC plasma level (32,257 mUI/mL). The erenumab treatment was immediately stopped. The last erenumab administration was performed on 4/7/2019, probably in correspondencewith the first 2 weeks of pregnancy, since her last period occurred from 8 to 13 June. The patient underwent all routine gynecological investigations, and spontaneously decided against amniocentesis. The serological fetal DNA test was normal. During the first trimester of pregnancy, the frequency of migraine increased up to 10 days/month. During the second trimester, migraine showed a marked improvement, and * Piero Barbanti [email protected]