Real-world effectiveness of onabotulinumtoxinA as first-line treatment in chronic migraine and sequential transition to anti-CGRP monoclonal antibodies: a retrospective multicenter study

BACKGROUND: Monoclonal antibodies (mAbs) targeting the Calcitonin Gene-Related Peptide (CGRP) pathway are safe and effective treatments for migraine prevention. However, the high cost of these novel therapies has led to reimbursement policies requiring patients to try multiple traditional preventives before access. Here, we evaluate the real-world effectiveness of onabotulinumtoxinA (BoNT-A) as first-line treatment and describe the sequential transition to anti-CGRP monoclonal antibodies in patients who did not achieve sufficient response, within the Polish chronic migraine treatment program. METHODS: In this retrospective cohort study, we included 94 patients with chronic migraine who received BoNT-A treatment according to the PREEMPT protocol every 3-4 months for 12 months as first-line treatment. Headache diaries and documentation were used to evaluate reductions in monthly headache days (MHD) and MIDAS scores. Patients were divided into two subgroups based on their response after three BoNT-A administrations: insufficient response (≤ 50% reduction in MHD) and sufficient response (> 50% reduction in MHD). RESULTS: We included 94 patients (93.62% female, age range 22-66 years). Following three BoNT-A injection cycles, 70 patients (74.47%) did not achieve the ≥ 50% response threshold and were sequentially transitioned to fremanezumab per programme protocol. In the insufficient response group, MHD decreased from 18.26 ± 4.46 to 13.90 ± 4.64 days (t(69) = 15.49, p < 0.001), representing a 23.9% reduction, while MIDAS scores decreased from 93.77 ± 41.80 to 61.69 ± 35.56 (t(69) = 10.22, p < 0.001, 34.2% reduction). In the sufficient response group (n = 24, 25.53%), MHD decreased from 17.83 ± 1.95 to 7.83 ± 1.83 days after 3 injections (56.1% reduction, t(23) = 31.97, p < 0.001), and further to 4.13 ± 1.77 days after 5 injections (76.7% reduction, t(22) = 32.59, p < 0.001). Pearson's correlation analysis revealed moderate positive correlation between MHD and MIDAS after 3 injections (r = 0.392, p < 0.001), which weakened substantially after 5 injections (r = 0.082, p = 0.691). Baseline MIDAS scores were numerically higher in the sufficient response group (116.62 ± 61.12 vs. 93.77 ± 41.80, t(92) = 2.04, p = 0.044); however, given the outcome-dependent nature of group allocation, this difference should not be interpreted causally or as a prognostic marker. For patients who did not experience sufficient improvement after the third BoNT-A administration, treatment was changed to fremanezumab. CONCLUSIONS: Our real-world data demonstrate that 74.47% of patients with chronic migraine did not achieve the ≥ 50% MHD reduction threshold after three onabotulinumtoxinA injections, supporting the current Polish therapeutic algorithm that allows sequential transition to anti-CGRP monoclonal antibodies for insufficient responders.