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Objective: To determine the real-world effectiveness and safety of erenumab after 6 months of treatment in chronic migraine patients with therapeutic resistance to multiple classes of prophylactic medication., Methods: The patients were recruited from the Headache Outpatient Clinic of the University Hospital Centre Zagreb, Croatia between March 2019 and November 2019. All participants received erenumab 70 mg for 6 months. Interviews with participants were conducted at baseline and after the treatment period. The following parameters were analysed: reduction percentage of monthly migraine days, monthly migraine days (MMDs), monthly non-migraine headache days (MNDs), monthly headache days (MHDs), pain intensity measured by the visual-analogue scale (VAS), monthly acute migraine medication intake and reported side-effects. Additionally, we analysed the data for migraine with and without aura separately., Results: There was a significant decrease in the mean value of headache frequency and pain intensity parameters after 6 months of treatment with erenumab. Out of the 54 participants included in the analysis, 70.37% had a ≥ 50% reduction in MMDs, while 40.74% had a ≥ 75% reduction. The mean values of MMDs and MHDs were reduced from 10.37 ± 0.38 to 4.59 ± 0.43 days (P < 0.001) and from 22.24 ± 0.70 to 9.74 ± 0.91 days (P < 0.001), respectively. Furthermore, the mean migraine VAS score decreased from 10.00 ± 0 to 6.69 ± 0.24 (P < 0.001). There was no significant difference in effectiveness between participants with migraine with and without aura. Nine participants reported side-effects., Conclusion: Our study indicates that erenumab is a safe and effective therapeutic option for chronic migraine patients., (Copyright © 2022 Elsevier B.V. All rights reserved.)