Back to the future: a case series on revisiting onabotulinumtoxinA for chronic migraine management after anti-CGRP therapies failure

Background: Chronic migraine (CM) management is still a challenge. Notwithstanding the success of anti-calcitonin gene-related peptide antibodies (anti-CGRP mAbs), not all patients respond to these treatments. Here, we revisit the efficacy of onabotulinumtoxinA (BTA) in patients who did not respond to anti-CGRP mAbs. Methods: This case series included 36 CM patients who demonstrated an insufficient response (<10% reduction in monthly headache days [MHD]) to anti-CGRP mAbs and who received a subsequent BTA treatment between December 2022 and February 2024. All patients had a minimum follow-up duration of six months with anti-CGRP mAb and BTA treatments. Results: The cohort comprised 12 patients (92% females, mean age of 49 years) affected by CM. Treatment with anti-CGRP mAbs produced in 7 (58.3%) patients an initial 20% reduction in MHD which, after a few months, was less than 10%; in 5 patients (41.6%) the response was >10% from the beginning of the treatment. A reduction in MHD of >50% was reported in 6 patients (50%) treated with BTA, and in 6 patients (50%) there was a less pronounced reduction (30-50%). Conclusions: This case series is the first report of patients who showed a meaningful response to BTA after an unsuccessful trial with anti- CGRP mAbs, suggesting a CGRP-independent action of BTA. However, due to the small sample size, further research is needed to support the proposal of a positive response to BTA in CM patients resistant to anti-CGRP mAbs and the consequent mechanistic implications.