Abstract
BackgroundSome variables have been proposed as predictors of efficacy of OnabotulinumtoxinA in chronic migraine patients, but data available are inconclusive. We aimed to analyse the influence of single nucleotide polymorphisms in the response to OnabotulinumtoxinA.MethodsWe included 156 female patients treated with OnabotulinumtoxinA accordingly to PREEMPT paradigm in three headache units. OnabotulinumtoxinA was offered to patients that had not responded to topiramate and at least one other preventative. Age at first procedure was 43.7 ± 11.8 years (16–74). Patients with a reduction of at least 50% in the number of migraine days after two OnabotulinumtoxinA procedures were considered as responders. We analysed 25 polymorphisms selected for their relevance regarding migraine pathophysiology and their association with migraine according to previously published genome-wide association studies. Genotyping was performed using KASP probes and a LightCycler-480 (Roche-Diagnostics). Allelic, genotypic frequencies and dominance/recesivity hypothesis of the allelic variants were compared between responders and non-responders by Fisher’s exact test.ResultsResponse to treatment with OnabotulinumtoxinA was achieved in 120 patients (76,9%). Two polymorphisms showed differences: CALCA rs3781719, where allele C represents 26.9% in responders and 40.9% in non-responders (p = 0.007, OR = 3.11 (1.33–7.26)); and TRPV1 rs222749, where allele A represents 4.17% in responders and 12.5% in non-responders (p = 0.013, OR = 3.29 (1.28–8.43)). No significant differences in rest of polymorphisms or clinical or demographic variables were found.ConclusionsPolymorphic variations of CALCA and TRPV1 genes might play a role as prognostic markers of efficacy of OnabotulinumtoxinA in chronic migraine female patients in our population.
Highlights
Some variables have been proposed as predictors of efficacy of OnabotulinumtoxinA in chronic migraine patients, but data available are inconclusive
Regarding the strength of association, the following values of Odds Ratio were obtained with confidence intervals of 95%: allele C related with a greater risk of non-response than allele T: [OR = 1.88 (1.06–3.32)] and, in relation to genetic models, the dominant model had a value of OR = 3.11 (1.33–7.26); the codominant model had a value of OR = 1.6 (0.85–3.00) and the recessive model had a value of OR = 1.2 (0.31–4.71)
Intervals of 95%: allele A related with a greater risk of non-response than allele G [OR = 3.29 (1.28–8.43)] and, in relation to genetic models, the dominant model had a value of OR = 2.47 (0.81–7.48); the codominant model had a value of OR = 2.40 (0.80–7.24) and the recessive model had a value of OR = 10.82 (1.09–107.45)
Summary
Some variables have been proposed as predictors of efficacy of OnabotulinumtoxinA in chronic migraine patients, but data available are inconclusive. OnabotulinumtoxinA (OnabotA) is considered a safe and effective therapy to manage CM, as was shown in the PREEMPT clinical program [2,3,4,5]. In a real-life clinical practice OnabotA pericranial injections effectively reduced headache and migraine days [5,6,7,8,9,10,11]. Molecular mechanism of action of OnabotA consists on cleaving SNAP-25 and, so, impairing intracellular vesicular fusion and down regulating release of pain. Moreno-Mayordomo et al The Journal of Headache and Pain (2019) 20:39 related neuropeptides, such as glutamate, substance P or CGRP [12, 13]. Decreasing peripheral sensitization by all these mechanisms, OnabotA would indirectly inhibit central sensitization [15]
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