This retrospective, real-world case series was conducted at the tertiary headache center of the Medical University of Innsbruck, including 196 patients with EM and CM who have received their first dose of a monoclonal CGRP-R-mAb (erenumab 70mg/month or 140mg/month) or a CGRP-ligand antibody (galcanezumab 120mg/month with a loading dose of 240mg or fremanezumab 225mg/month or 675mg/quarterly) between April 2018 and December 2021. During the study period, eptinezumab was not approved for the preventive treatment of migraine in adults in the European Union and was therefore not included in the registry.
Headaches were classified in accordance with the latest International Classification of Headache Disorders, 3rd edition (ICHD-3).  Patients with >1 and <15 headache days/month were diagnosed with EM and patients with ≥ 15 headache days/month were classified as CM.  In Austria, treatment with a CGRP-mAb is reimbursed in patients 1) aged ≥ 18 years, 2) with ≥ 4 migraine days per month, 3) no therapeutic response, the occurrence of side effects or contraindications of > 3 preventive migraine medications such as beta-blockers, antiepileptics, calcium channel blockers, onabotulinumtoxinA, tricyclic antidepressants.
Additional headache diagnoses (referred to as “other” in table 1) included tension-type headache, trigeminal-autonomic headache and secondary headaches like headache attributed to traumatic injury to the head or headache attributed to increased cerebrospinal pressure. Medication overuse (MO) was classified according to the ICHD-3 as regular use of one or more non-opioid analgesics (NSAIDs, paracetamol or acetylsalicylic acid) on 15 or more days/month or regular use of triptans, ergotamines, opioids or combination analgesics on 10 or more days/month for headache treatment in the last 3 months.  Inpatient and/or outpatient withdrawal due to MO was recorded.
Prior preventive migraine medications included beta-blockers (metoprolol, propranolol), angiotensin receptor blocker (candesartan), anti-epileptic drugs (topiramate, valproic acid), calcium channel blocker (flunarizine), tricyclic antidepressant (amitriptyline), selective serotonin and norepinephrine reuptake inhibitor antidepressants (venlafaxine), and tanacetum parthenium. Preventive therapies, which were used by less than 5 patients were included in the “Other” group (gabapentin, duloxetine, pregabalin, amalium, citalopram, zonisamide, mirtazapine, tizanidine). OnabotulinumtoxinA was only used in patients with CM and administered according to the “PREEMPT” injection protocol.  Psychiatric comorbidities included depression, anxiety and/or panic disorders as well as eating disorders. Disease duration was calculated for each patient from the first migraine attack until the first treatment with a monoclonal antibody.
Patients were considered as non-responders, if they did not show a therapeutic response, defined as ≥ 50% reduction of monthly migraine days (MMDs) in EM and ≥ 30% reduction of MMDs in CM after an adequate treatment duration of 3 months. Lack/Loss of efficacy and side effects causing a switch to another mAB/CGRP-ligand were documented. If the mAb was discontinued for other reasons (wishing to conceive, reimbursement issues), the patients were included in the category “other”. Patients switching antibody treatment, regardless of whether non-response, loss of efficacy, or adverse events led to treatment discontinuation, were adviced to pause CGRP-mAb treatment at least 2 to 3 months before starting a new mAb. If the patient received a CGRP-receptor antibody as the first drug, they were treated with a CGRP-ligand antibody as second therapeutic attempt and vice versa. Demographic and clinical characteristics were collected from the electronic patient documentation database. As a detailed history was taken during the initial consultation and follow-up visits to the headache outpatient clinic, there was no missing data for the selected variables, except for those patients who requested further care in general practice. Due to the lack of follow-up data, these patients were not included in the final analysis.
Statistical analyses were performed using SPSS Statistics (version 27.0; IBM Corporation, Armonk, NY, US). Normal distribution of data was assessed with the Kolmogorov-Smirnoff Test. Data are given as mean ± standard deviations (SD) for normally distributed data and medians and interquartile ranges [IQR] for non-normally distributed data. Continuous variables, categorical variables are presented as percentages. The Student´s t-test or Mann-Whitney-U test were applied as appropriate. We ran a multinomial logistic regression model adjusting for: gender (male, female), age, headache-free-days (yes/no), psychiatric disorder (yes/no), number of previously used prophylactic medications, mean monthly migraine days, medication-overuse (yes/no), withdrawal (yes/no). The level of significance was set at p<0.05. As this was a retrospective data analysis, a sample size calculation was not performed.