Erenumab is a monoclonal antibody targeting the calcitonin gene–related peptide receptor. Randomized, placebocontrolled trials demonstrated that erenumab is effective in migraine prevention, both episodic and chronic [1, 2]. Moreover, erenumab has a demonstrated clinically relevant efficacy in chronic migraine (CM) patients with associated medication overuse (MO), which is a renowned hard-to-treat group of patients. According to the current classification of the International Headache Society (ICHD-3)[3], medication overuse headache is defined as a headache occurring for at least 15 days per month in a patient with a pre-existing primary headache that develops because of regular overuse of symptomatic headache medication (use for≥ 10 or 15 days per month depending on the medication) for more than 3 months. The term medication overuse is used to describe the frequent intake of headache medication in a person with a primary headache disorder without causing an increase in headache frequency. At present, real-life clinical evidence regarding erenumab efficacy is still missing. The aim of the present study is to assess erenumab efficacy in patients with CM and MO.

An observational multicenter study was performed in six Italian hospitals. Inclusion criteria were the following: age≥ 18 years old; diagnosis of CM and MO according to the ICHD-3; previous treatment failures of at least 3 prophylaxes; no cardio-and/or cerebro-vascular disorders. Patients were treated with erenumab 70 mg every 4 weeks. If no clinical response was observed after 12 weeks, a dose increase to 140 mg was attempted. Data about outcome, adverse events, abortive medication consumption, and disability (Migraine Disability Assessment Score Questionnaire [MIDAS]; Headache Impact Test [HIT-6]) were collected on a monthly basis. The primary endpoint was to evaluate the reduction in the headache frequency at 4, 12, and 24 weeks of treatment. Secondary endpoints were the following: reduction in headache intensity, symptomatic medication intake, MIDAS, and HIT-6 score. The percentage of non-responders (< 30% headache-days reduction), partial responders (< 50%), and responders (> 50%) was obtained at weeks 12 and 24. Eighty-four consecutive patients were enrolled (65 F, 19 M). Mean age was 48.2 years (SD 8.1), with a mean disease duration of 11.03 years (SD 7.3). On average patients had already failed 5.3 (SD 1.8) previous migraine prophylaxis. The mean patient estimated headache-days frequency was 21.5 (SD 5.9) days per month, with a mean monthly medication intake of 25.2 (SD 13.3) analgesics per month, mainly NSAIDs and triptans. No patient discon treatment and no new safety concerns were identified. A significant reduction from baseline to weeks 4, 12, and 24 in total and severe headache days (p< 0.0001), total analgesic consumption (p< 0.0001), triptan consumption (p= 0.001), non-steroidal anti-inflammatory drug consumption (p= 0.003), pain intensity (p= 0.001), MIDAS (p< 0.0001), and HIT-6 score (p= 0.01) per month was found (Fig. 1a). At week 12, 22.1% of patients classified as non-responder, 12.9% as partial responder, and 65% as