Real-World Lessons with Fremanezumab as the Third Available CGRP Monoclonal Antibody in a Third-Level Hospital: Focus on the Factors Predicting Response

<b>Background:</b> Fremanezumab was the third CGRP antibody available in our hospital. This examination of our experience with fremanezumab is focused on identifying the predictors of response. <b>Methods:</b> This was a prospective observational study in which we included high-frequency episodic/chronic migraine (HF/CM) patients who were prescribed fremanezumab during the year 2023. Our research involved collecting data on their demographic details, diagnoses made, treatments received, prophylactic measures taken in the past, and any comorbid conditions present. The number of headaches was documented for one quarter prior to and after the initiation of fremanezumab. <b>Results:</b> Eighty-nine patients received fremanezumab (86.5% female, 45.8 ± 12.5 years old, 70.1% naive). The headache days decreased from 21.1 ± 7.6 to 12.4 ± 11.2 days during the initial three months of the treatment, and a total of 55 patients (61.8%) exhibited a response rate of ≥50%. Six out of ten patients refractory to erenumab for at least 6 months responded to fremanezumab. Totals of 17 and 26 patients had been treated at least with galcanezumab or erenumab. The elements influencing non-response were as follows: prior failure to respond to both erenumab and galcanezumab (<i>p</i> < 0.0001), HF/CM length (11.9 ± 7.1 years in non-responders vs. 5.8 ± 4.8 in responders; <i>p</i> < 0.001), the presence of fibromyalgia (<i>p</i> < 0.001), anxiety-depression (<i>p</i> < 0.001), an almost daily headache baseline (>28 days/month) (<i>p</i> < 0.0001), and analgesic overuse (<i>p</i> < 0.0001). The response rate was unaffected by age and experience. After a multivariate logistic analysis, almost daily headaches (<i>p</i> < 0.001), a length of HF/CM > 6 years (<i>p</i> = 0.015), and anxiety-depression (<i>p</i> = 0.017) remained significant. Fremanezumab showed excellent tolerance. <b>Conclusions:</b> These real-life results confirm the efficacy of fremanezumab. The main factors associated with a lack of response were almost daily/daily headaches and a disease duration > 6 years. Half of the patients who failed to respond to erenumab improved on fremanezumab, making it sensible to switch to a treatment with a different mechanism of action, but trying a third anti-CGRP treatment in patients with no response to both a receptor-targeted and a ligand-targeted CGRP antibody hardly seems justifiable from our experience.