Impact of duration of chronic migraine on long-term effectiveness of monoclonal antibodies targeting the calcitonin gene-related peptide pathway-A real-world study

Objective: We assessed whether the effectiveness of monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway changes according to the duration of chronic migraine (CM) over 12 months. Background: In most patients, CM is a progressive disease starting with episodic migraine. Longer CM duration might be associated with more difficult treatment, probably because the mechanisms underlying chronicization are strengthened. Therefore, early treatment of CM could lead to better outcomes compared with later treatment. Methods: This cohort study included individuals with CM treated with anti-CGRP mAbs in two tertiary headache centers from April 2019 to May 2023. The primary outcome included a change in monthly migraine days (MMDs) from baseline to the third trimester of treatment, 10-12 months. Secondary outcomes established whether response to anti-CGRP mAbs has a more rapid onset in individuals with shorter CM duration compared with longer duration; they included change in MMDs, monthly headache days (MHDs), and days and number of intakes of acute medication during each trimester compared to baseline. Additional outcomes included persisting MMDs, MHDs, and days and number of intakes of acute medication during each trimester of treatment. Patients were compared across tertiles of the overall CM duration. Results: The study included 335 individuals with CM, with a median (interquartile range [IQR]) age of 48(39-57) years; 270 (80.6%) were women. Patients in the highest tertile of CM duration (aged 18-60 years) were older than patients in the lower duration tertiles (0-7 years and 8-18 years, respectively), with a median (IQR) age of 56(48-64) years compared with 42(31-50) years, and 48(39-56) years, respectively (p=0.025); however, this difference was likely due to a correlation between age and disease duration. The change in MMDs from baseline to the last trimester of treatment (10-12 months) was comparable across tertiles of CM duration (median [IQR] -12[-18 to -5] days, -12[-17 to -6] days, and -12[-18 to -4] days; p=0.946). No difference emerged in secondary outcomes, suggesting a similar time to onset of anti-CGRP mAbs effect across all tertiles of CM duration. Conclusions: Our data showed that anti-CGRP mAbs are effective and have a rapid onset of action in CM regardless of disease duration. Plain language summary Episodic migraine can progress to chronic migraine, which is characterized by frequent headache attacks and significantly impacts daily life. We predicted that treating patients with chronic migraine with monoclonal antibodies targeting the calcitonin gene-related peptide pathway sooner after diagnosis would be more effective than starting this treatment after the patient had chronic migraine for a longer time. We showed that these antibodies are equally effective for patients who were diagnosed earlier and those who had chronic migraine for a long time, indicating that they are efficacious regardless of patients' duration of migraine.