Impact of Botulinum Toxin Versus CGRP Monoclonal Antibodies on Return Visits and Acute Medication Use in Chronic Migraine: First Real-World, Multicenter, Head-to-Head Analysis Using TriNetX

Background: Botulinum toxin type A and calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) are widely used preventive treatments for chronic migraine. However, real-world comparative evidence regarding their effects on health-care utilization and acute medication use remains lacking. Objectives: To directly compare the real-world effectiveness of botulinum toxin and CGRP mAbs in reducing migraine-related return visits and acute triptan medication prescription use among patients with chronic migraine across a large, multicenter cohort. Methods: A retrospective cohort analysis was conducted using data collected from the TriNetX global health-care database for the period from 2018 to 2024. Adults with a diagnosis of chronic migraine were assigned to botulinum toxin or CGRP mAb cohorts on the basis of prescription records. Propensity score matching was used to balance key demographic, clinical, and comorbidity variables between the cohorts. The primary outcomes were (1) migraine-related return visits and (2) acute triptan prescription risk within 1 year of treatment initiation. Sensitivity analyses were conducted by expanding diagnostic criteria to include broader headache codes ( International Classification of Diseases, Tenth Revision, Clinical Modification R51), and subgroup analyses were performed to examine outcome consistency across age, sex, and comorbidity strata. Results: After propensity score matching, each cohort comprised 10,140 patients. Botulinum toxin was associated with a significantly lower acute triptan prescription risk (hazard ratio: 0.513, 95% confidence interval: 0.481–0.546, p < 0.001), whereas migraine-related return visit rates were comparable between the cohorts. The increased triptan prescription risk observed in the CGRP mAb cohort persisted across sensitivity and subgroup analyses. In the expanded cohorts, higher migraine recurrence was observed among CGRP mAb users. Conclusions: This multicenter real-world study demonstrated that botulinum toxin was associated with a superior reduction in acute triptan prescription risk compared with CGRP mAbs in patients with chronic migraine. These findings were robust across diverse subgroups and sensitivity analyses, supporting phenotype-driven preventive therapy selection to optimize acute medication control and health-care resource utilization.