Table 4.

Mechanistic and clinical scenarios of anti-CGRP mAbs

(Super-) Responders to mAbs	Non-responder to erenumab		Non-responder to anti-CGRP ligand mAbs
	Responder to switch (ligand)	Non-responder to switch (ligand)	Responder to switch (erenumab)	Non-responder to switch (erenumab)
Molecular mechanism
CGRP antagonism sufficient	CGRP antagonism sufficient but: 1. CGRP receptor block insufficient 2. CGRP must be blocked elsewhere	CGRP antagonism insufficiently blocked and/or other molecules may be involved	CGRP antagonism sufficient but: 1. circulating CGRP block insufficient 2. other molecules acting on the CGRP receptor or similar receptor (AMY1) must be blocked	CGRP antagonism insufficiently blocked and/or other molecules may be involved
Mode of Action
Peripheral CGRP antagonism is sufficient	Peripheral CGRP antagonism is sufficient	Peripheral CGRP antagonism is probably insufficient and: 1. More central action may be required 2. Other CGRP-independent pathways are involved peripherally or centrally	Peripheral CGRP antagonism is sufficient	Peripheral CGRP antagonism is probably insufficient and: 1. More central action may be required 2. Other CGRP-independent pathways are involved peripherally or centrally