Switching strategies with CGRP monoclonal antibodies: an observational study in a headache clinic

Background Migraine is a disabling neurological disorder that greatly impacts quality of life and productivity. Calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) have recently improved preventive migraine therapy. However, some patients show limited efficacy, loss of response, or adverse effects, prompting interest in switching between mAbs. Objective The objective of this work is to evaluate the effectiveness of switching between mAbs in chronic migraine/high-frequency episodic migraine (CM/HFEM) patients and to identify potential clinical predictors of response. Methods This single-centre, real-life, prospective study was conducted in a tertiary hospital headache unit which includes patients with CM or HFEM who switched from one mAb to another without a treatment gap greater than 1 month. Monthly headache days (MHDs), monthly migraine days (MMDs), monthly analgesic consumption (MAC), and medication overuse (MO) were recorded 3 months before and at three and 6 months after switching. Subanalyses were performed based on the mechanism of action (anti-ligand vs. anti-receptor), reason for switch (lack or loss of efficacy), and clinical predictors. Results Eighty-five patients (52.2 ± 9.6 years; 87.1% female; 95.3% CM) were included. At 3 months post-switch, reductions were observed in MHDs (−5.8 days, p < 0.001), MMDs (−5.8 days, p < 0.001), MAC (−5.6 days, p < 0.001), and MO (−22.2%, p = 0.001). At 6 months, these improvements persisted. A ≥ 50% response was achieved in 29.4% (25/85) of patients at month 3 and 32.9% (28/85) at month 6. One-third of patients whose switch included a change in mechanism of action responded, while none of those who underwent anti-ligand to anti-ligand switch showed a reduction of MHDs >50%. Both patients with loss and lack of efficacy to the first mAb improved significantly, though early response was more frequent among those with prior loss of efficacy. Obesity and concomitant tension-type headache were associated with poorer early response, while migraine with aura predicted better late response. Conclusion Switching between mAbs could be an effective strategy for some CM and HFEM patients who fail initial mAb therapy, rescuing approximately one-third of non-responders. The therapeutic benefit seems to be greater when the second antibody targets a different mechanism of action. These real-world findings support the use of individualized switching strategies in refractory migraine management.