CGRP and PTX3 as Predictors of Efficacy of Onabotulinumtoxin Type A in Chronic Migraine: An Observational Study

Headache. 2018 Jan;58(1):78-87. doi: 10.1111/head.13211. Epub 2017 Nov 13.

Abstract

Objective: The aim of this study is to find a relation between several biomarkers in peripheral blood and outcome after treatment with onabotulinumtoxin A (OnabotA).

Background: OnabotA is an effective treatment in chronic migraine (CM). Different studies have tried to find predictors of response to treatment, either with clinical characteristics, neuroimaging features, or molecular biomarkers; however, it is still not possible to predict the individual outcome.

Methods: We measured serum levels of biomarkers of inflammation (IL-6, IL-10, TNF-α, and hs-CRP), endothelial dysfunction (PTX3 and sTWEAK), blood-brain barrier disruption (cFN), brain damage (S100b, NSE), and trigemino-vascular activation (CGRP) by ELISA in a group of CM patients treated with OnabotA and healthy controls. After 24 weeks, patients were classified in two groups according to their outcome considering variations in headache frequency: nonresponders (nonimprovement or improvement <50%) and responders (improvement >50%). We compared baseline levels of biomarkers between these groups.

Results: Sixty-two patients diagnosed with CM (IHS 2013 criteria) who fulfilled criteria for treatment with OnabotA and 24 healthy controls were included. Fifteen patients did not respond to treatment (24.2%) and 47 were responders (75.8%). Pentraxin 3 (PTX3) serum levels (1455.4 ± 487.5 pg/mL versus 720.3 ± 334.1 pg/mL, P < .0001) and calcitonin gene-related peptide (CGRP) serum levels (133.1 ± 86.6 ng/mL versus 58.2 ± 91.7 ng/mL, P = .004) were significantly higher in responders than nonresponders. Serum basal levels of PTX3 >1000 pg/mL (AUC 0.908; 95% CI: 0.827-0.990) and CGRP >50 ng/mL (AUC 0.800; 95% CI: 0.652-0.947) were associated with good response to OnabotA treatment.

Conclusions: These results show that molecular markers of trigeminovascular activation (CGRP) and endothelial dysfunction (PTX3) are associated with response to OnabotA and may act as new biomarkers for the selection of treatment in chronic migraineurs.

Keywords: CGRP; PTX3; chronic migraine; onabotulinumtoxin A; outcome; predictors.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Aged
  • Botulinum Toxins, Type A / therapeutic use*
  • C-Reactive Protein / metabolism*
  • Calcitonin Gene-Related Peptide / blood*
  • Chronic Disease / drug therapy
  • Cytokines / blood
  • Female
  • Humans
  • Male
  • Middle Aged
  • Migraine Disorders / blood*
  • Migraine Disorders / drug therapy*
  • Neuromuscular Agents / therapeutic use*
  • Retrospective Studies
  • Serum Amyloid P-Component / metabolism*
  • Treatment Outcome

Substances

  • Cytokines
  • Neuromuscular Agents
  • Serum Amyloid P-Component
  • PTX3 protein
  • C-Reactive Protein
  • Botulinum Toxins, Type A
  • onabotulinum toxin A
  • Calcitonin Gene-Related Peptide