anti-CGRP monoclonal antibodies (anti-CGRP mAbs) represent a highly effective prophylactic treatment for chronic migraineurs, but for some subjects they are ineffective. We aimed to determine if OnabotulinumtoxinA (BoNT/A) treatment may be helpful in these cases. We collected data from fourteen chronic migraineurs who attended our Headache Center and who did not benefit from anti-CGRP mAbs treatment. After anti-CGRP mAbs failure, these patients underwent at least one BoNT/A treatment according to the PREEMPT protocol. We then compared the variation in headache days (DOH), pain intensity (NRS), and symptomatic medication intake (ADI) before and after anti-CGRP mAbs therapy and before and after BoNT/A treatment: we confirmed that the interruption of anti-CGRP mAbs treatment had actually been due to a lack of benefit in terms of DOH (19.21 ± 7.58 days and 20.29 ± 8.32 days; p = 0.74), NRS (7.64 ± 0.75 vs 7.57 ± 1.01; p = 0.85) and ADI (42.86 ± 52.74 vs 45.64 ± 52.82; p = 0.79). All patients started BoNT/A therapy after discontinuing anti-CGRP mAbs. After a period without treatment, therapy with BoNT/A caused a significant reduction in DOH (23.86 ± 6.97 vs. 11.36 ± 10.10, p = 0.010), ADI (47.07 ± 51.19 vs. 20.50 ± 21.42, p = 0.010) and NRS (8.07 ± 1.00 vs. 6.64 ± 1.60, p = 0.014), improving clinical conditions in patients non-responders to anti-CGRP mAbs. It is not well established on which basis pharmacological resistance to anti-CGRP mAbs develops in such refractory patients. Still, these data may point towards a mechanism of pain relief that could not be solely related to CGRP pathways activity, thus being a good rescue therapy in resistant headache management, although further data are needed. Our preliminary results suggest that BoNT/A may be a promising salvage therapy option when anti-CGRP mAbs are ineffective, but evidence requires confirmation from basic research and in larger, uncontrolled, prospective studies in chronic migraineurs.
