16th European Headache Congress

Prof.

Chair

Differential effects of an anti-CGRP antibody and botulinum toxin in experiments of meningeal nociception

Invited speaker

Invited lecture

Non-paralytic botulinum toxins as preventive therapeutic treatments of the trigeminal system

The pain of migraine is driven by activity of HCN2 ion channels

Professor

Expression of vasopressin and its receptors in migraine-related regions in CNS and the trigeminal system: Influence of sex

Migraine

Trigeminal neuralgia

Abstract text (incl. figure legends and references) Objective; Hypothalamus is a key region in migraine attacks. In addition, women are disproportionately affected by migraine. The calcitonin gene-related peptide (CGRP) system is an important key player in migraine pathophysiology. CGRP signaling could be a target of hormones that influence migraine. Our aim is to identify the expression of vasopressin and its receptors in the brain and in the trigeminovascular system with focus on the migraine-related regions and, furthermore, to examine the role of sex on expression of neurohormones in the trigeminal ganglion. Methods; Rat brain and trigeminal ganglia were carefully harvested and proteins and genes were analyzed by immunohistochemistry and real-time PCR, respectively. The number of vasopressin and its receptors immunoreactive neurons in male and female TG were calculated. Results; Vasopressin and its receptors immunoreactivity were found in migraine-related areas within the brain and in the trigeminal ganglion, predominantly in neuronal cytoplasm. There were no differences in the number of positive cells expression of CGRP and vasopressin in the trigeminal ganglion between male and female rats. In contrast, the number of RAMP1 (CGRRP receptor) and vasopressin receptors (V1aR and V1bR) immunoreactive cells were higher in female compared to male. Vasopressin and its receptors mRNA were expressed in both hypothalamus and trigeminal ganglion; however, the vasopressin mRNA level was significantly higher in the hypothalamus. Conclusions; A better understanding of potential hormonal influences on migraine mechanisms is needed to improve treatment of female migraineurs. It is intriguing that vasopressin is an output of hypothalamic neurons that influences areas associated with migraine. Therefore, vasopressin might be important hypothalamic components that contribute to migraine pathophysiology.

Abstract lecture

Switching OnabotulinumtoxinA and Monoclonal Antibodies Anti-CGRP in Severe, Drugs-Resistant Chronic Migraine

CGRP inhibitors in the clinic

Abstract text (incl. figure legends and references) Question: To assess the long-term therapeutic impact of anti-calcitonin gene related protein (CGRP) monoclonal antibodies (anti-CGRP mAbs) in drugs-resistant patients with chronic migraine (CM) with no or partial response to OnabotulinumtoxinA (BTX). Methods: A retrospective, cohort study, enrolling 78 severe CM patients (&gt;80% with medication-overuse [MO]), resistant to ≥3 preventative treatments, and treated with BTX and then with anti-CGRP mAbs. The study consisted of two observational periods of 9 months. A varying non-observational period of at least 6-months occurred after the last BTX treatment. The primary endpoints were the absolute change from baseline in monthly headache days (MHDs), response rates and persistence in MO at 3-, 6- and 9-months follow-up in the two cohorts separately. The secondary endpoint was the change in acute medications use per month. Finally, we performed a last observation carried forward analysis for primary and secondary endpoints. Results: After nine months of treatment, retention rate ranged from 91.0% to 62.2% in the BTX-A cohort and from 96.2%, to 76.9% in the anti-CGRP mAbs cohort (fig.1). Approximatively 20% of patients discontinued both treatments due to inefficacy. After 9 months of treatment, 22.4% with BTX-A and 65.0% with anti-CGRP mAbs achieved a ≥50% response (fig.2). Two patients were migraine-free in the CGRP cohort. BTX-A and anti-CGRP mAbs reduced MHDs at month-9.0 by -5.0 and -12.0, respectively, and decreased the number of MO patients at month-9 (75.5% and 25% persisted in MO, respectively [fig. 3]). Only two patients discontinued treatments due to AEs. Conclusions: Our findings in drugs-resistant CM patients indicate that patients who discontinued BTX-A undergoing anti-CGRP mAbs treatment showed a substantial clinical improvement in migraine related outcomes. Stopping BTX-A in patients with no response/partial response after the first two cycles and switching to an anti-CGRP mAb appears a viable option.

Placebo effects in clinical trials of anti-CGRP monoclonal antibodies for migraine prevention

Abstract text (incl. figure legends and references) OBJECTIVE: Commonly used indirect treatment comparison (ITC) methods, such as network meta-analyses, assume the presence of a common comparator across trials. For placebo (PBO)-controlled trials, PBO usually serves as the common comparator. Recent literature indicates that differences in route of administration (ROA) across PBO arms of clinical trials in pain disorders may contribute to differences in PBO effect. We conducted a meta-regression on PBO data from anti-CGRP monoclonal antibody (mAb) trials for migraine prevention to quantify the potential impact of ROA on PBO reduction in monthly migraine days (MMDs) across weeks 1–12. METHODS: A systematic literature review was conducted in June 2021 to identify relevant PBO data from randomized clinical trials of anti-CGRP mAbs in migraine prevention. A generalized linear model was fitted to the extracted PBO data, with migraine type (EM/CM) and proportion of patients with ≥2 failed preventives as covariates. RESULTS: An IV ROA for the PBO arm was a predictor for higher MMD reduction while episodic migraine, and a higher proportion of patients having ≥2 failed preventives were predictors of lower MMD reduction over weeks 1–12 in the PBO arms of studies investigating anti-CGRP mAbs. CONCLUSIONS: Our results indicate that PBO ROA differences may warrant the use of ITC methods which do not assume the presence of a common comparator when comparing anti-CGRP mAbs in migraine prevention. Further research should be considered.

Acute and preventive modulation of the trigeminal system: What the future will bring

On Demand

Strauss 1

SciSe 4

Scientific session

SciSe 4
Acute and preventive modulation of the trigeminal system: What the future will bring

Termin

Chair

Programm

SciSe 4Acute and preventive modulation of the trigeminal system: What the future will bring

Termin

Chair

Programm

SciSe 4
Acute and preventive modulation of the trigeminal system: What the future will bring