Gender-related stress factors and emotional perception in migraine: a structured online questionnaire in migraine patients and controls.

BACKGROUND: While migraine is markedly prevalent in women, gender-related phenotype differences were rarely assessed. For this reason, we investigated, through a multicenter observational cross-sectional study, based on an online questionnaire, gender-related differences in stress factors, emotions, and pain perception in migraine patients and controls and their impact on migraine severity. METHODS: The study was designed as an online questionnaire. The link was emailed to healthy subjects (C) and migraine patients (MIG) (age 18-75, education ≥ 13 years) recruited during the first visit in 8 Italian Headache Centers adhering to Italian Society for Headache Study (SISC). The questionnaire included personal/social/work information, the Perceived Stress Scale, the Romance Quality Scale, the Emotion Regulation Questionnaire, the Beck Anxiety Inventory, the Body Perception Questionnaire, the pain perception, and a self-assessment of migraine severity in the last 3 months. RESULTS: 202 MIG and 202 C completed the survey. Independently from gender, migraine was characterized by higher pain sensitivity and more severe partner relationships. The female gender, in MIG, exhibited higher anxiety scores, body awareness, and reduced emotional suppression. Body awareness and emotional suppression were discriminating factors between genders in control and migraine groups without relevant influence on disease features. Perceived perception of migraine severity was similar between genders. CONCLUSION: Gender-related emotional and stress factors did not contribute to delineate a distinct phenotype in migraine men and women. The possible impact of emotional and stress factors characterizing genders could be considered for a single case-tailored therapeutic approach.

Evaluation of the risk of hypertension in patients treated with anti-CGRP monoclonal antibodies in a real-life study.

OBJECTIVE: To explore the rate of hypertension incoming in patients treated with monoclonal antibodies against the calcitonin gene-related peptide. BACKGROUND: The monoclonal antibodies blocking the calcitonin gene-related peptide are unquestionable effective in the prevention of migraine. Despite this, the development of hypertension has been detected in some patients. METHODS: This was a retrospective study conducted at the University Hospital of Modena. Patients were visited quarterly up to 1 year. RESULTS: Globally, no significant increase in the blood pressure was detected. The 5.7% of the patients developed a significant increase in their blood pressure. In particular, patients with a pre-existing hypertension were more likely to have a significant increase in the blood pressure. CONCLUSION: The risk of developing hypertension during a treatment with anti-calcitonin gene-related peptide monoclonal antibodies seems low. Anyway, patients with a pre-existing hypertension should be cautiously monitored because they are more likely to develop hypertension.

Long-Term Treatment Over 52 Weeks with Monthly Fremanezumab in Drug-Resistant Migraine: A Prospective Multicenter Cohort Study.

BACKGROUND: Real-world studies on fremanezumab, an anti-calcitonin gene-related peptide monoclonal antibody for migraine prevention, are few and with limited follow-up. OBJECTIVE: We aimed to evaluate the long-term (up to 52 weeks) effectiveness and tolerability of fremanezumab in high-frequency episodic migraine and chronic migraine. METHODS: This s an independent, prospective, multicenter cohort study enrolling outpatients in 17 Italian Headache Centers with high-frequency episodic migraine or chronic migraine and multiple preventive treatment failures. Patients were treated with fremanezumab 225 mg monthly. The primary outcomes included changes from baseline (1 month before treatment) in monthly headache days, response rates (reduction in monthly headache days from baseline), and persistence in medication overuse at months 3, 6, and 12 (all outcome timeframes refer to the stated month). Secondary outcomes included changes from baseline in acute medication intake and disability questionnaires scores at the same timepoints. A last observation carried forward analysis was also performed. RESULTS: A total of 90 patients who received at least one dose of fremanezumab and with a potential 12-month follow-up were included. Among them, 15 (18.0%) patients discontinued treatment for the entire population, a reduction in monthly headache days compared with baseline was reported at month 3, with a significant median [interquartile range] reduction in monthly headache days (- 9.0 [11.5], p < 0.001). A statistically different reduction was also reported at month 6 compared with baseline (- 10.0 [12.0]; p < 0.001) and at 12 months of treatment (- 10.0 [14.0]; p < 0.001). The percentage of patients with medication overuse was significantly reduced compared with baseline from 68.7% (57/83) to 29.6% (24/81), 25.3% (19/75), and 14.7% (10/68) at 3, 6, and 12 months of treatment, respectively (p < 0.001). Acute medication use (days and total number) and disability scores were also significantly reduced (p < 0.001). A ≥ 50% response rate was achieved for 51.9, 67.9, and 76.5% of all patients at 3, 6, and 12 months, respectively. Last observation carried forward analyses confirmed these findings. Fremanezumab was well tolerated, with just one patient discontinuing treatment because of adverse events. CONCLUSIONS: This study provides evidence for the real-world effectiveness of fremanezumab in treating both high-frequency episodic migraine and chronic migraine, with meaningful and sustained improvements in multiple migraine-related variables. No new safety issue was identified.

Galcanezumab for the treatment of chronic migraine and medication overuse headache: Real-world clinical evidence in a severely impaired patient population.

BACKGROUND: Galcanezumab is a monoclonal antibody acting against the calcitonin gene-related peptide approved for the preventive treatment of migraine. The aim of this article is to explore its effectiveness and safety of galcanezumab in chronic migraine (CM) with medication overuse-headache (MOH). METHODS: Seventy-eight patients were consecutively enrolled at the Modena headache center and followed up for 15 months. Visits were scheduled every 3 months, and the following variables were collected: the number of migraine days per month (MDM); the painkillers taken per month (PM); the number of days per month in which the patient took, at least, one painkiller; the six-item headache impact test; and the migraine disability assessment questionnaire (MIDAS) score. Demographic features of the analyzed sample were collected at the baseline and adverse events (AEs) were collected at every visit. RESULTS: After 12 months, galcanezumab significantly reduced the MDM, the PM, the number of days on medication, the HIT-6 as well as the MIDAS scores (all p < .0001). The greatest amelioration was obtained in the first trimester of treatment. A higher MDM, a higher NRS score at the baseline, and a higher number of failed preventive treatments negatively predict the CM relief at the year of treatment. No serious AEs were registered and only one drop-out was due to AE. CONCLUSIONS: Galcanezumab is effective and safe for the treatment of patients affected by CM and MOH. Patients with a higher impairment at the baseline may found less benefits with galcanezumab.

Monoclonal anti-CGRP antibodies in post-menopausal women: a real-life study.

INTRODUCTION: Migraine usually ameliorates after menopause. However, 10-29% of women still experience migraine attacks after menopause, especially if menopause is surgical. The use of monoclonal antibodies against the calcitonin gene-related peptide (CGRP) is changing the landscape of migraine treatment. This study aims to explore the effectiveness and safety of anti-CGRP monoclonal antibodies in women in menopause. METHODS: Women affected by either migraine or chronic migraine and treated with an anti-CGRP monoclonal antibody for up to 1 year. Visits were scheduled every 3 months. RESULTS: Women in menopause displayed a similar response compared to women of childbearing age. Among women in menopause, the women experiencing surgical menopause seemed to exhibit a similar response compared to the ones experiencing physiological menopause. Erenumab and galcanezumab displayed similar effectiveness in women in menopause. No serious adverse events were registered. DISCUSSION: The effectiveness of anti-CGRP monoclonal antibodies is almost the same between women in menopause and women of childbearing age, without appreciable differences between the different antibodies.

Predictors of response to erenumab after 12 months of treatment.

OBJECTIVE: Erenumab is a monoclonal antibody acting against calcitonin gene-related peptide receptor and approved for the preventive treatment of chronic migraine. The aim of the present study is to identify clinical predictors of good response in patients with chronic migraine and medication overuse-headache. MATERIAL AND METHODS: This was a retrospective single-center not funded study. Enrolled patients were affected by chronic migraine and medication overuse-headache treated with erenumab monthly, up to 1 year. At 1 year, patients were classified as good responders if they displayed a ≥50% reduction in the number of headache days per months compared to the baseline. RESULTS: After 1 year, a significant improvement in the number of headache days per months, analgesic consumption, 6-items headache impact test, and migraine disability assessment questionnaire scores were obtained compared to the baseline. Patients who obtained a ≥50% reduction in the number of headache days per month compared to the baseline displayed a longer history of medication overuse-headache, a higher number of painkillers taken per month at the baseline and a higher number of failed preventive treatments in the past. CONCLUSIONS: Patients with longer medication overuse-headache duration, higher analgesic intake, and a higher number of previous preventive treatment failures may receive less benefit with erenumab.

Serum levels of allopregnanolone, progesterone and testosterone in menstrually-related and postmenopausal migraine: A cross-sectional study.

BACKGROUND: Reduced blood or cerebrospinal fluid levels of allopregnanolone are involved in menstrual cycle-linked CNS disorders, such as catamenial epilepsy. This condition, like menstrually-related migraine, is characterized by severe, treatment-resistant attacks. We explored whether there were differences in allopregnanolone, progesterone and testosterone serum levels between women with menstrually-related migraine (MM, n = 30) or postmenopausal migraine without aura who had suffered from menstrually-related migraine during their fertile age (PM, n = 30) and non-headache control women in fertile age (FAC, n = 30) or post-menopause (PC, n = 30). METHODS: Participants were women with migraine afferent to a headache centre; controls were female patients' acquaintances. Serum samples obtained were analyzed by HPLC-ESI-MS/MS. RESULTS: In menstrually-related migraine and postmenopausal migraine groups, allopregnanolone levels were lower than in the respective control groups (fertile age and post-menopause) (p < 0.001, one-way analysis of variance followed by Tukey-Kramer post-hoc comparison test) while progesterone and testosterone levels were similar. By grouping together patients with migraine, allopregnanolone levels were inversely correlated with the number of years and days of migraine/3 months (p ≤ 0.005, linear regression analysis). CONCLUSION: Decreased GABAergic inhibition, due to low allopregnanolone serum levels, could contribute to menstrually-related migraine and persistence of migraine after menopause. For the management of these disorders, a rise in the GABAergic transmission by increasing inhibitory neurosteroids might represent a novel strategy.