Table 4 Mechanistic and clinical scenarios of anti-CGRP mAbs
From: Mode and site of action of therapies targeting CGRP signaling
(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 |