16th European Headache Congress

Chair

Precision medicine: in what way can genetics be of help

Prof. Dr.

Invited speaker

Invited lecture

Predicting the response to CGRP-ergic medication

Targeting therapy for idiopathic intracranial hypertension

Professor

Putative predictors of super-response to CGRP monoclonal antibodies

Abstract text (incl. figure legends and references) Question: Are there putative predictors of super-response to CGRP monoclonal antibodies? Methods: This was a unicentric prospective study between February 2019 and April 2022. We collected demographic, clinical, comorbid, and therapeutic data. We applied validated clinical scales to assess baseline severity and therapeutic response. We defined super-responders as patients who achieved a consistent ≥75% reduction in migraine frequency after 6 months of treatment and non-responders as patients with reduction &lt;25%. We used SPSS v.23 for statistical analysis and compared groups of super-responders to non-responders using univariate linear logistic regression. Results: From a total of 63 patients and after excluding 8 (12.8%) (short follow-up), we analyzed 42 patients. Median age was 44 years (IQR 52) and 41 (97.6%) were women. Twenty-one (50%) had chronic migraine with median duration of 22.9 years (IQR 56), 17 (40.5%) had medication overuse and 24 (57.1%) responded to triptans. We treated patients with Erenumab (n=31), Fremanezumab (n=7) and Galcanezumab (n=4). We had 29 super-responders and 13 non-responders. We found a statistically significant association between super-responders and lower baseline frequency of migraine (OR=0.901), episodic migraine (OR=0.096) and response to triptans (OR=5.000). After treatment, there was a statistically significant association between reduction of migraine frequency and lower HURT scale score (OR=0.771) and decreased headache intensity (OR=0.644). We noticed a trend towards statistically significant results between super-responders and &gt;3 failed preventives (p=0.072) and lower baseline intense episodes (p=0.085). Conclusions: In CGRP monoclonal antibody treatment, episodic migraine, response to triptans and lower baseline intense episodes may be potential predictors of super-response. HURT scale may be appropriate to monitor these patients. This real-life data may allow better selection and management of patients.

CGRP inhibitors in the clinic

Migraine

Abstract lecture

Prof.

Pharmacogenetic assessments of treatment response in cluster headache

Abstract text (incl. figure legends and references) Background: The response to cluster headache treatments has a high interindividual variation. To date, treatment response has only been assessed by candidate gene approach and no investigations into metabolic pathways have been performed. Question: To investigate the association between polygenetic risk of cluster headache and treatment response to first line cluster headache treatments. Additionally we investigated known functional variants of CYP3A4 and the response to verapamil1. Further, to replicate previous single nucleotide polymorphisms found to be associated with treatment response in cluster headache and/or migraine. Methods: 508 cluster headache patients diagnosed according International Classification of Headache Disorders ere genotyped and participated in a semi-structured interview to evaluate treatment response. Polygenetic risk score was calculated by effect retrieved from meta-analyzing the latest two GWAS on cluster headache. Results: We confirm previous findings that inferior treatment response associates with chronicity of cluster headache no evidence for response to first-line abortive and preventive treatment was predicted by a high genetic risk of cluster headache or functional variants of CYP3A4. We did not found support of the suggested genetic variants previously reported to be associated with treatment response to triptans or verapamil. Conclusion: The clinically relevant variation in treatment response for cluster headache is unlikely to be influenced by genetic factors and other factors should be searched.

Cluster headache 

Genetics genomics | RNA

Salivary CGRP and erenumab response: towards precision medicine in migraine

Abstract text (incl. figure legends and references) Question: It is still to be shown if there is a correlation between baseline CGRP levels and prediction of response to these treatments or if CGRP levels are modified and how with treatment. We aimed (i) to analyze salivary CGRP levels in migraine patients (ii) to predict erenumab response from pre-treatment CGRP levels and (iii) to evaluate CGRP change post-treatment. Methods: This is a prospective observational study that measured salivary CGRP levels in healthy controls (HC), episodic migraine (EM) and chronic migraine (CM) patients. Participants collected saliva samples at baseline and, patients who were candidates to receive erenumab 140 mg, also collected saliva after 3 doses of treatment. We quantified CGRP-like immunoreactivity (CGRP-LI) by ELISA and we performed an analysis at baseline and post-treatment through generalized linear mixed models. Results: At baseline, a higher headache frequency was associated with higher CGRP levels, being those even higher in presence of depressive symptoms. A cut-off point of 103.75 pg/mL was estimated to differentiate migraine from controls with an 80.3% of accuracy. We also found that higher pre-treatment salivary CGRP levels were statistically significantly associated to a higher probability of having 50% or greater reduction in headache frequency in EM patients, but not in CM. After 12-weeks of treatment with erenumab 140, salivary CGRP levels from patients within all spectrum of migraine frequency converged to similar CGRP values. In contrast, in patients with concomitant depressive symptoms, this convergence did not happen. Interpretation: Patients with migraine not only have higher CGRP levels compared to controls, but also the presence of depressive symptoms seems to increase salivary CGRP levels and we have evidence, for the first time, that salivary CGRP concentration is associated with treatment response to erenumab.

SciSe 8
Precision medicine

Termin

Chair

Programm

SciSe 8Precision medicine

Termin

Chair

Programm

SciSe 8
Precision medicine