CGRP and VIP Levels as Predictors of Efficacy of Onabotulinumtoxin Type A in Chronic Migraine

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Onabotulinumtoxin type A (onabotA) has shown efficacy in chronic migraine (CM). Its precise mechanism of action, however, is unknown.


To analyze a potential relationship between calcitonin gene-related peptide (CGRP) and vasoactive intestinal peptide (VIP) levels and response to onabotA in CM.


Adult patients with CM were recruited. Matched healthy subjects with no headache history served as controls. CGRP and VIP levels were determined in samples obtained from the right antecubital vein by ELISA outside of a migraine attack and having taken no symptomatic medication prior to treatment with onabotA. OnabotA was administered according to the PREEMPT protocol every 12 weeks for at least two treatment cycles. A patient was considered as a moderate responder when both: (1) moderate-severe headache episodes were reduced by between 33 and 66%; (2) subjective benefit in a visual scale of 0-100 was recorded by the patient of between 33-66%. Patients were considered as excellent responders when both items improved >66%. Those without improvement of at least one-third in the two items were considered as nonresponders.


We assessed plasma samples from 81 patients with CM and 33 healthy controls. CGRP and VIP levels were significantly increased in CM population vs controls. CGRP and, to a lesser degree, VIP levels were significantly increased in responders vs nonresponders. For CGRP, a threshold of 72 pg/mL positively correlated with 95% of nonresponders. The probability of being a responder to onabotA was 28 times higher in patients with a CGRP level above the threshold of 72 pg/mL. Even though the sensitivity for the calculated threshold for VIP was poor, the probability that CM patients with low CGRP levels will respond to onabotA was significantly higher in those patients with high VIP levels.


Interictal CGRP and, to a lesser degree, VIP levels measured in peripheral blood are of great help in predicting response to onabotA.

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