Cerebral Blood Flow and Other Predictors of Responsiveness to Erenumab and Fremanezumab in Migraine—A Real-Life Study

Abstract

IntroductionMonoclonal antibodies (mAbs) showed efficacy in migraine prevention. The aim of this study was to check if baseline clinical parameters and cerebral blood flow (CBF) measured by transcranial Doppler (TCD) may help predict mAbs efficacy.MethodsElectronic charts of migraineurs treated with erenumab or fremanezumab, with baseline TCD evaluations were collected, including data on migraine type, pain localization, monthly migraine days (MMD), medication overuse headache (MOH), mean blood flow velocity (Vm), and pulsatility index (PI) in cerebral arteries.ResultsA total of 123 patients were enrolled, mean age 38, 75 years, 87 with chronic migraine, 61 with MOH, 72 were good responders (GR), and reported ≥50% reduction in MMD, 43 ≥75% reduction in MMD. Baseline Vm values in MCAs were significantly lower in GR as compared with non-responders. MAbs responsiveness ≥50% was positively associated with unilateral pain localization (OR: 6.53, 95% CI: 2.01–23.93; p = 0.003) and HIT-6 score (OR: 1.14, 95% CI: 1.01–1.30; p = 0.036) whereas negatively associated with Vm in right MCA (OR: 0.96, 95% CI: 0.92–0.99; p = 0.012), and having no relatives with migraine (OR: 0.40, 95% CI: 0.16–0.95; p = 0.040).ConclusionsBaseline Vm in MCA is lower in mAbs GR as compared with non-responders which may reflect increased secretion of CGRP with further vasodilation in GR. Simple clinical features and baseline CBF in anterior circulation might help to predict the patient's responsiveness.

Predicting response to CGRP-monoclonal antibodies in patients with migraine in Japan: a single-centre retrospective observational study

“…Our results suggest that ≥ 50% CGRPmAb response is significantly associated with older age, fewer MHD, and fewer prior treatment failures, and can be predicted based on age, total prior treatment failures, and immunorheumatologic medical history. Several parameters that are reportedly associated with response, such as medication overuse [11,17,19], unilateral pain localisation [15], medical history of psychiatric disease [14,20], and MMD [18], were not significantly different between responders and non-responders in the present study.…”

“…The literature to date has shown that the response to CGRPmAbs is positively associated with a lower number of failed preventative medications [11][12][13][14], unilateral pain localisation [13][14][15], better response to triptans [13,16], lower number of monthly analgesic intakes at baseline [11,17,18], shorter duration of medication-overuse headache (MOH) [11,13,17,19], and lower body mass index (BMI) [13], and negatively associated with the existence of psychiatric conditions [14,20]. However, the results of these real-world studies have not always been consistent.…”

Clinical evaluation of super-responders vs. non-responders to CGRP(-receptor) monoclonal antibodies: a real-world experience

“…Despite several attempts, clear predictors of response could not be determined in the registration trials. In a few real-world studies, unilateral pain localization, and triptan responsiveness were positively associated with a better treatment response [ 17 – 21 ]. On the contrary, psychiatric comorbidities, a long disease duration and a high number of previously failed preventive treatments were associated with a lower response [ 17 , 18 , 22 – 26 ].…”

Blocking the CGRP Receptor: Differences across Human Vascular Beds

“…Atogepant displays the largest potency difference (35-210 times more potent in human middle meningeal artery), which seems favorable in view of the cardiovascular profile. However, efficacy, as well as safety, also depend on many other factors, such as plasma-protein binding, dosing, dosing intervals, duration of receptor antagonism in vivo and metabolism of the drug, as well as patient characteristics, such as the potential predominance of CGRP in the pathophysiology of their migraine attacks [30,31] and/or genetic polymorphisms in the CGRP receptor gene components [32]. Telcagepant, ubrogepant and zavegepant show a Schild plot slope in h coronary arteries that does not differ from unity, whereas for atogepant, olcegepant and gepant, the Schild slope is significantly less than unity.…”