Background and Purpose To evaluate the 1‐year effectiveness and tolerability of galcanezumab in real life and the prognostic indicators of persistent response. Methods High‐frequency episodic migraine (HFEM) and chronic migraine (CM) patients treated with galcanezumab who completed a 1‐year observation were enrolled. The primary outcomes assessed during the 12 months (V1–V12) were the change in monthly migraine days (MMDs) from baseline and the response rates ≥50% in MMDs (MMD ≥50% RR). The secondary outcomes were changes in pain intensity (numerical rating scale [NRS]) and in monthly acute medication intake (MAMI). Results We enrolled 191 patients (77.5% CM). Twenty‐three patients (12%) dropped out, two for nonserious adverse events. At least 40% of patients took add‐on standard preventives from baseline to V12. At V12, MMDs were reduced by 6.0 days in HFEM and by 11.9 days in CM patients (both p < 0.00001); NRS and MAMI were also decreased in both groups (p < 0.00001). One‐hundred eight (56.5%) patients presented MMD ≥50% RR for 9 cumulative months (interquartile range=8): we defined this value as the cutoff for a persistent response. Persistent responders were less likely to have a higher body mass index (BMI) (p = 0.007) but more frequently had a good response to triptans (p = 0.005) and MMD ≥50% RR at V1 (p < 0.0000001). Patients without a persistent response were on add‐on therapy for longer periods of time (p < 0.001). Conclusions Galcanezumab was effective and well‐tolerated in the 1‐year term, with most patients presenting MMD ≥50% RR for at least 9 months. Triptan response, lower BMI, and MMD ≥50% RR in the first month emerged as predictive factors for a persistent response.

Objective To investigate in real-life the conversion from chronic migraine (CM) to episodic migraine (EM), specifically to EM with High-Frequency (HFEM: 8–14 monthly migraine days, MMDs), Medium-Frequency (MFEM, 4–7 MMDs), and Low-Frequency EM (LFEM, 0–3 MMDs), and its persistence during 1 year of treatment with galcanezumab. Methods Consecutive CM patients treated with galcanezumab completing 1 year of observation were enrolled. We collected data on MMDs, pain intensity (Numeric Rating Scale, NRS score), and monthly acute medication intake (MAMI) from baseline (V1) to the 12-month visit (V12). Results Of the 155 enrolled patients, 116 (around 75%) reverted to EM at every visit and 81 (52.3%) for the entire 1-year treatment. Patients with older onset age ( p = 0.010) and fewer baseline MMDs ( p = 0.005) reverted more frequently to EM. At V12, 83 participants (53.5%) presented MFEM or LFEM. Patients reverted to MFEM or LFEM for 7 months (25th 1, 75th 11). The medication overuse discontinuation rate at V12 was 82.8% and occurred for 11 months (25th 8, 75th 12). From baseline to V12, the MAMI decreased by 17 symptomatic drugs ( p < 0.000001) while the NRS score reduced by almost 2 points ( p < 0.000001). A consistent transition to EM for the entire treatment year was observed in 81 (52.3%) patients. Discussion The 1-year GARLIT experience suggests that more than half of CM patients treated with galcanezumab persistently reverted to EM in real life. Trial registration ClinicalTrials.gov NCT04803513. Supplementary Information The online version contains supplementary material available at 10.1007/s00415-022-11226-4.

Calcitonin gene-related peptide (CGRP) is probably the most potent vasodilator in cerebral circulation. Forty years after its discovery, the new CGRP-targeted therapy monoclonal antibodies, and the small molecule gepants, are now available for clinical practice. While randomized controlled trials and real-world experience consistently demonstrated the high efficacy and tolerability of monoclonal antibodies, limited evidence is available to characterize gepants fully. Depending on pharmacokinetics, these CGRP receptor antagonists can be used for acute (ubrogepant, rimegepant, and the not yet approved zavegepant) or preventive (atogepant and rimegepant) migraine treatment. Randomized placebo-controlled trials demonstrated gepants efficacy in treating acute attacks to obtain 2 h pain freedom in about 20% of patients and pain relief in about 60%, while up to 60% of treated patients with episodic migraine may experience a 50% reduction in monthly migraine days. The most common treatment-related emergent adverse events were gastrointestinal (nausea, constipation) for the acute or preventive use. No vascular or hepatic concerns have emerged so far. More studies are ongoing to investigate gepant tolerability and safety also if associated with monoclonal antibodies targeting CGRP and other therapeutic classes. Gepants are also under investigation to treat other painful and non-painful conditions. Real-life studies are necessary to confirm the trials’ findings and investigate more practical clinical aspects.

Background: We aimed to investigate if the carotid intima-media thickness (IMT) at baseline and the HAD2S score, composed of the sum of single risk factors (hypertension, age ≥ 75 years, diabetes, dyslipidemia, smoking), were predictive of plaque progression. Methods: We performed a retrospective analysis on real-life prospectively collected data from patients with any detectable carotid plaque at follow up. The plaque score, calculated at baseline (T0) and at a median follow up of 36.6 months (IQR 39.6–34.3) (T3), was defined as 0: no plaque or stenosis < 30%; 1: stenosis in the range 30–49%; 2: in the range 50–69%; 3: in the range 70–99% and 4: occlusion. Carotid IMT was measured at T0 and T3; HAD2S score was calculated at baseline. Results: We included 340 patients with a mean age of 69.9 (9.1) years and 25.3% subjects had plaque progression. Individuals with progression had a median HAD2S score of 3 (1) while those without progression had 2 (1). Patients with progression had a mean baseline IMT of 0.86 (0.17) while those without progression had 0.77 (0.18) (p < 0.0001). A correlation between progression and baseline IMT was found (p = 0.002). Conclusion: Baseline IMT could be considered a predictor of progression. Patients with progression had an HAD2S score higher than those without evolution.

IntroductionThe mechanisms subtending the increased stroke risk in migraine with aura (MA) are not fully understood. Our study aims to evaluate if the clinical profile in stroke patients with MA differentiates from those without MA.MethodsWe retrieved the prospective registered electronic clinical dossiers of adult patients younger than 60 years with acute ischemic stroke admitted in four hospitals between January 2016 and June 2022. Patients were classified by the history of MA (MA+ and MA–).ResultsWe identified 851 stroke patients (59 MA+, 6.9%). Compared to MA−, MA+ patients were characterized by younger age (44.0 ± 10.6 vs 50.1 ± 8.2 years), female sex (59.3% vs 29.0%), and affected by cryptogenic (OR 2.594 95% CI 1.483–4.537), and cerebellar stroke (OR 3.218 95% CI 1.657–6.250; p ≤ 0.001 for all comparisons). After adjusting for age and sex, MA+ patients presented less frequently hypertension (OR 0.349 95% CI 0.167–0.470; p=0.005) and dyslipidemia (OR 0.523 95% CI 0.280–0.974; p = 0.041). After adjusting also for risk factors, the MA+ group had less frequently symptomatic large vessel stenosis (OR 0.126 95% CI 0.017–0,924; p = 0.042) and clinical atherosclerosis (OR 0.103 95% CI 0.014–0.761; p = 0.026), while intima–media thickness did not differ (p = 0.395).DiscussionCryptogenic and cerebellar stroke and fewer vascular risk factors and clinical atherosclerosis seem to characterize stroke patients with MA.