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

Domínguez, Carlos; Vieites‐Prado, Alba; Pérez‐Mato, María; Sobrino, Tomás; Rodríguez‐Osorio, Xiana; López, Ana; Campos, Francisco; Martínez, Francisco Andrés García; Castillo, José; Leira, Rogelio

doi:10.1111/head.13211

Cited by 65 publications

(89 citation statements)

References 36 publications

(85 reference statements)

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“…Inflammation is present in migraine . Previously, our group showed that chronic migraineurs had elevated IL‐6 levels and lower IL‐10 levels compared with individuals without headache . We confirmed this observation in our cohort of participants, in which the chronic migraine group presented more IL‐6 and less IL‐10 in comparison with the control group.…”

Section: Discussionsupporting

confidence: 89%

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Periodontal inflammation is related to increased serum calcitonin gene‐related peptide levels in patients with chronic migraine

Leira

Ameijeira

Domínguez

et al. 2019

Journal of Periodontology

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Background Recently, a relationship was found between periodontitis and chronic migraine. Calcitonin gene‐related peptide (CGRP) is a key element in migraine pathophysiology. However, no information exists of the potential association between periodontal inflammation and CGRP in chronic migraine. The aim of the study was, therefore, to investigate whether there is a link between periodontitis and peripheral levels of CGRP in a cohort of patients with chronic migraine. Methods We included 102 chronic migraineurs and 77 age‐ and sex‐matched individuals free of headache/migraine. Full‐mouth periodontal parameters were recorded and the periodontal inflamed surface area (PISA) was calculated to quantify the periodontal inflammatory status for each participant. Sociodemographic data and comorbidities were assessed by means of a standard questionnaire. We collected blood samples and serum concentrations were done for CGRP, interleukin (IL)‐6 and IL‐10. Results In the chronic migraine group, patients with periodontitis had greater levels of serum CGRP (19.7 ± 6.5 versus 15.3 ± 6.2 pg/mL, P < 0.0001) and IL‐6 (15.1 ± 9.2 versus 9.6 ± 6.3 pg/mL, P < 0.0001) while non‐significant differences were observed with IL‐10 (2.0 ± 1.0 versus 2.8 ± 1.5 pg/mL, P = 0.675) concentrations than those without periodontitis. PISA was independently associated with CGRP in patients with chronic migraine (β = 0.003; 95% confidence interval: 0.001 to 0.006, P = 0.031). PISA correlated positively with CGRP (r = 0.236; P = 0.017) and IL‐6 (r = 0.262; P = 0.008) in chronic migraine. Conclusions Periodontal inflammation is associated with increased circulating levels of CGRP in chronic migraineurs. Elucidating the exact mechanisms through which periodontitis and CGRP are linked in these patients deserves further investigation.

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Section: Discussionsupporting

confidence: 89%

“…Particularly, it has been shown that chronic migraineurs have interictal elevated circulating levels of CGRP . For instance, onabotulinumtoxin A (OnabotA), a common treatment option for chronic migraine, is capable of reducing interictal CGRP serum levels and it could be a predictor of good response to this therapy …”

Section: Introductionmentioning

confidence: 99%

Periodontal inflammation is related to increased serum calcitonin gene‐related peptide levels in patients with chronic migraine

Leira

Ameijeira

Domínguez

et al. 2019

Journal of Periodontology

Self Cite

View full text Add to dashboard Cite

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“…Accordingly, reduced sensitivity to molecules that activate C‐meningeal nociceptors through TRPV1 and TRPA1 and reduce the CGRP release might contribute to the clinical efficacy of BTX‐A in migraine. In people with CM, an effective treatment was correlated with higher serum CGRP levels, 76,77 that decrease in the interictal phase 73 . These results assume that the effectiveness of BTX‐A depends on the inhibition of CGRP release from peripheral sensory afferents and the consequent reduction of its serum level.…”

Section: Btx‐a and The Cgrp Pathwaymentioning

confidence: 81%

Dual Therapy With Anti‐CGRP Monoclonal Antibodies and Botulinum Toxin for Migraine Prevention: Is There a Rationale?

et al. 2020

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Objective.-To narratively review the pathophysiological rationale of dual therapy with anti-calcitonin gene-related peptide monoclonal antibodies and botulinum toxin type A in treatment-resistant chronic migraine prevention.Background.-For the prevention of chronic migraine, several pharmacological therapies are available, including oral medications, botulinum toxin type A, and the newly approved monoclonal antibodies targeting calcitonin gene-related peptide or its receptor. However, monotherapy does not yield benefits in some affected individuals, which raises the question of whether dual therapy with monoclonal antibodies and botulinum toxin type A hold promise in patients with treatment-resistant chronic migraine.Method.-We searched MEDLINE for articles published from database inception to December 31st, 2019. Publications were largely selected from the past 10 years but commonly referenced and highly regarded older publications were not excluded.Results.-Preclinical data suggest that anti-calcitonin gene-related peptide monoclonal antibodies and botulinum toxin type A have synergistic effects within the trigeminovascular system. Of note, findings indicate that fremanezumab -an antibody targeting the calcitonin gene-related peptide -mainly prevents the activation of Aδ-fibers, whereas botulinum toxin type A prevents the activation of C-fibers.Conclusion.-There is currently only indirect preclinical evidence to support a rationale for dual therapy with anti-calcitonin gene-related peptide monoclonal antibodies and botulinum toxin type A for chronic migraine prevention. Rigorous studies evaluating clinical efficacy, safety, and cost-effectiveness are needed. Abbreviations: BBB blood-brain barrier, BTX-A botulinum toxin typeA, CGRP calcitonin gene-related peptide, CM chronic migraine, CNS central nervous system, HT high-threshold, mAb monoclonal antibody, SNARE soluble N-ethylmaleimide-sensitive factor attachment protein receptor, TG trigeminal ganglion, TNC trigeminal nucleus caudalis, TRPA1 transient receptor potential ankyrin 1, TRPV1 transient receptor potential cation channel subfamily V member 1, WDR wide-dynamic range (

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“…Seeking clinical biomarkers that may contribute to predict how our patients will evolve is an important goal for physicians since it helps to manage both patient and physician’s expectations, better understand the mechanisms of CM, and optimize the therapeutic resources . So far, most predictors of response to OnabotulinumtoxinA are not only based on clinical features, but also in molecular biomarkers such as calcitonin gene‐related peptide (CGRP) . However, results are limited or controversial, and are based on the presence of a good response (>50%).…”

Section: Introductionmentioning

confidence: 99%

“…16 So far, most predictors of response to OnabotulinumtoxinA are not only based on clinical features, [17][18][19][20][21] but also in molecular biomarkers such as calcitonin gene-related peptide (CGRP). [22][23][24] However, results are limited or controversial, and are based on the presence of a good response (>50%).…”

Section: Introductionmentioning

confidence: 99%

Short and Mid‐Term Predictors of Response to OnabotulinumtoxinA: Real‐Life Experience Observational Study

et al. 2020

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Objective To identify clinical predictors of excellent response to OnabotulinumtoxinA in patients with chronic migraine (CM) at 6 and 12 months of follow‐up. Background Clinical predictors of response to OnabotulinumtoxinA are scarce and have not been clearly reproduced and analyzed in detail. So far, predictors of response to OnabotulinumtoxinA assess response in general or good response, but not an excellent response. Methods Cohort study of patients attended in a specialized Headache Clinic in treatment with OnabotulinumtoxinA were classified according to their improvement in frequency: no‐response (<25%) and excellent response (≥75%). A comparative analysis was carried out at 6 and 12 months identifying clinical predictors of excellent response to OnabotulinumtoxinA at each timepoint. Results Data were collected from 221 patients. After 6 and also 12 months, we observed a statistically significant mean reduction in frequency and analgesic intake. At month 6, independent variables associated with excellent response (OR[95%CI]) were daily headache frequency (0.32[0.14‐0.74]; P = .005), medication overuse (MO) (2.28[1.19‐4.37]; P = .013), and a higher ratio of migraine days/month (MDM) (1.20[1.10‐1.45]; P = .018) at baseline. At month 12, independent predictors of excellent response were patients with less than 30 years of migraine evolution (0.43[0.23‐0.82]; P = .011), presence of anxiety (0.44[0.23‐0.85]; P = .018), and aura (0.48[0.25‐0.92]; P = .037). Excellent responders showed a higher improvement rate in pain intensity at 6 and 12 months. Conclusions Patients with daily frequency and MO show a clinical improvement in short‐term. Patients with comorbidities who start treatment earlier in the course of the disease need a longer duration of treatment. The profile of response to treatment with OnabotulinumtoxinA determines its minimum treatment duration and the timepoint of a meaningful response.

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

Abstract: 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.

Cited by 65 publications

References 36 publications

Periodontal inflammation is related to increased serum calcitonin gene‐related peptide levels in patients with chronic migraine

Periodontal inflammation is related to increased serum calcitonin gene‐related peptide levels in patients with chronic migraine

Dual Therapy With Anti‐CGRP Monoclonal Antibodies and Botulinum Toxin for Migraine Prevention: Is There a Rationale?

Short and Mid‐Term Predictors of Response to OnabotulinumtoxinA: Real‐Life Experience Observational Study

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