Background: Preclinical evidence supports the immunoregulatory role of calcitonin gene-related peptide (CGRP) in migraine pathophysiology. The increasing use of anti-CGRP therapies in patients with migraine and other comorbidities raises the question whether the potential use of anti-CGRP monoclonal antibodies (CGRP-mAbs) therapies in combination with other immunological therapies is effective and safe. Methods: This multicenter study included patients with migraine receiving CGRP-mAbs combined with immunosuppressive and immunomodulatory treatments. Clinical and demographic data, treatment history, laboratory markers and treatment-emergent adverse events (TEAEs) were analyzed. Effectiveness outcomes included the change in monthly migraine days (MMD) and monthly headache days (MHD) at 3, 6, 9 and 12 months, alongside the > 50% response rate. Moreover, autoimmune disease progression was also evaluated. We explored differences between patients with and without autoimmune disease activation. Results: Among 89 patients, there were 80 (90%) females with a mean age of 50 years (SD: 11), who had a high prevalence of psychiatric comorbidities (anxiety 44%, depression 49%) and medication overuse (68%). Patients receiving immunological treatments experienced significant reductions in MMD and MHD, with MMD decreasing from 16 (SD: 7) at baseline to 9 (SD: 8) at 6 months, and MHD dropping from 23 (SD: 8) to 17 (SD: 11). A 50% response in MMD was achieved by 46% at 6 months. TEAEs were reported in 28%, most commonly constipation (16%) and dizziness (9%). Conclusions: CGRP-mAbs therapies combined with immunological treatments appear effective and safe in patients with autoimmune diseases. Larger prospective studies are necessary to confirm these findings and optimize management strategies.

Introduction. Human immunodeficiency virus (HIV) infected patients are at increased risk of cardiovascular disease (CVD). Multidetector computed tomography (MDCT) stratifies cardiovascular risk in asymptomatic patients with subclinical atherosclerosis. The aim of this study was to determine the ability of MCTD and clinical and laboratory parameters to assess subclinical CVD progression in HIV patients. Material and methods. Prospective longitudinal cohort study of patients with at least 10 years of HIV infection and 5 years of antiretroviral therapy history, low cardiovascular risk and monitored for 6 years (2015-2021). All patients underwent clinical assessment, blood analysis, carotid ultrasound, and gated MDCT in 2015 and 2021. Results. Sixty-three patients (63.5% male) with a mean age of 49.9 years (standard deviation [SD], 10.5) were included in 2015; 63 of them were followed until 2021. Comparing the results from 2015 with those from 2021, Systematic Coronary Risk Estimation-2 (SCORE2) was 2.9% (SD, 2.1) vs. 4.4% (SD, 3.1); Multi-Ethnic Study of Atherosclerosis score (MESA risk) was 3.4 (SD 5.8) vs. 6.0 (SD 8.6); coronary artery calcification CAC) score >100 was 11.1% vs. 25.4% (P < 0.05); and 11% vs. 27% had carotid plaques (P = 0.03). Conclusions. After six years of follow-up, an increase in SCORE2, carotid plaques, CAC scoring and MESA risk was observed. MDCT findings, along with other clinical and laboratory parameters, could play an important role as a marker of CVD progression in the evaluation of patients with HIV and low cardiovascular risk.

Background: Fremanezumab was the third CGRP antibody available in our hospital. This examination of our experience with fremanezumab is focused on identifying the predictors of response. Methods: This was a prospective observational study in which we included high-frequency episodic/chronic migraine (HF/CM) patients who were prescribed fremanezumab during the year 2023. Our research involved collecting data on their demographic details, diagnoses made, treatments received, prophylactic measures taken in the past, and any comorbid conditions present. The number of headaches was documented for one quarter prior to and after the initiation of fremanezumab. Results: Eighty-nine patients received fremanezumab (86.5% female, 45.8 ± 12.5 years old, 70.1% naive). The headache days decreased from 21.1 ± 7.6 to 12.4 ± 11.2 days during the initial three months of the treatment, and a total of 55 patients (61.8%) exhibited a response rate of ≥50%. Six out of ten patients refractory to erenumab for at least 6 months responded to fremanezumab. Totals of 17 and 26 patients had been treated at least with galcanezumab or erenumab. The elements influencing non-response were as follows: prior failure to respond to both erenumab and galcanezumab (p < 0.0001), HF/CM length (11.9 ± 7.1 years in non-responders vs. 5.8 ± 4.8 in responders; p < 0.001), the presence of fibromyalgia (p < 0.001), anxiety–depression (p < 0.001), an almost daily headache baseline (>28 days/month) (p < 0.0001), and analgesic overuse (p < 0.0001). The response rate was unaffected by age and experience. After a multivariate logistic analysis, almost daily headaches (p < 0.001), a length of HF/CM > 6 years (p = 0.015), and anxiety–depression (p = 0.017) remained significant. Fremanezumab showed excellent tolerance. Conclusions: These real-life results confirm the efficacy of fremanezumab. The main factors associated with a lack of response were almost daily/daily headaches and a disease duration > 6 years. Half of the patients who failed to respond to erenumab improved on fremanezumab, making it sensible to switch to a treatment with a different mechanism of action, but trying a third anti-CGRP treatment in patients with no response to both a receptor-targeted and a ligand-targeted CGRP antibody hardly seems justifiable from our experience.

Background: Serum 25‐hydroxyvitamin D (25[OH]D) concentrations have been shown to be low in patients with migraine, but results are controversial regarding the current role of vitamin D in migraine severity. Using a case–control design, we aimed to evaluate serum 25(OH)D levels in a group of females with high‐frequency episodic migraine/chronic migraine (HF/CM) and analyze its association with headache frequency and serum calcitonin gene–related peptide (CGRP) levels.Methods: Serum 25(OH)D levels were measured in 97 females with HF/CM (age 48.9 ± 9.4 years) and 146 healthy females (47.4 ± 8.1 years). Participants taking vitamin D supplements were excluded. Serum concentrations of 25(OH)D were determined by electrochemiluminescence (Roche, Germany), and CGRP levels were measured by enzyme‐linked immunosorbent assay (Abbexa, UK).Results: Mean 25(OH)D levels in females with HF/CM (median [interquartile range] 19.0 [13.0–24.5] ng/mL) were below the values considered for insufficiency or deficiency and significantly lower than controls (25.0 [19–29.8] ng/mL; p < 0.0001). Fifty (51.5%) patients with HF/CM had levels below 20 ng/mL. There was no significant association between vitamin D levels and monthly headache days (Spearman's rank correlation coefficient [rho]: −0.086; p = 0.404) or with serum α (rho: 0.114; p = 0.267) and β‐CGRP (rho: 0.113; p = 0.276) levels. Serum 25(OH)D levels in females with HF/CM with a minimum daily sunlight exposure were significantly higher than those without (23.0 [15.0–26.0] ng/mL vs. 14.0 [10.0–20.0] ng/mL; p < 0.001). Females with HF/CM who performed exercise had higher, albeit not significant, plasma 25(OH)D levels than those who did not (21.0 [15.5–28.0] ng/mL vs. 16.5 [12.0–24.0] ng/mL; p = 0.059).Conclusions: Serum concentrations of 25(OH)D were low in many patients with HF/CM. Because there was no correlation with migraine frequency or serum CGRP levels, this deficiency seems to be a direct consequence of the migraine impact. Our data do not support either a relationship of 25(OH)D levels with migraine severity or the use of vitamin D supplements as a specific migraine treatment, although further studies are needed.

Background: Cluster headache (CH) is one of the most disabling primary headaches. Nowadays, it is unknown if it has an impact on reducing life expectancy. Methods: We calculated years of potential life lost (YPLL) in deceased individuals from a CH registry of a third‐level hospital, using as cutoff the estimated life expectancy for our general population according to their sex and year of death. Furthermore, a descriptive and comparative analysis of the main causes of death, risk factors, and toxic habits was carried out. Results: There were 25 deaths among the 152 individuals included. Twenty‐one (84%) died earlier than expected with a mean of 9.14 YPLL ( p = 0.001). Cancer was the most common cause of death in CH patients (64% of deaths vs. 28.5% expected in general population, p ≤ 0.001). Eighty percent and 45% of our deceased patients were smokers and 60% and 45% regular alcohol consumers at the diagnosis of CH and at death, respectively. The percentage of smokers at diagnosis was significantly higher than that in the reference population (80% vs. 33.2%, p < 0.001). There was a significantly higher frequency of arterial hypertension (76% vs. 19.82%, p < 0.001) and diabetes mellitus (40% vs. 7.8%, p < 0.001) at death in CH individuals compared to general population. Conclusions: CH implies a loss of almost one decade of life expectancy by an increase in cancer deaths. Tobacco and alcohol consumption seem to be the main underlying causes. These results call for an action plan for a better management of CH patients since their diagnosis.

Objective: This study aimed to evaluate demographic characteristics, treatment effectiveness, and safety outcomes in patients with migraine undergoing anti‐calcitonin gene‐related peptide (CGRP) treatments regarding the presence of autoimmune diseases. Background: CGRP has an important role in migraine pathophysiology through neuronal modulation in the trigeminovascular nociceptive system and activation of neuro‐inflammatory cascades. We hypothesized that autoimmune diseases may influence treatment response and safety profiles in patients with migraine treated with anti‐CGRP treatments. Methods: This was a retrospective multicenter, age‐ and sex‐matched cohort study in headache units/headache clinics in Spain and United Kingdom between May 2024 and May 2025 including patients treated with CGRP monoclonal antibodies from prospectively collected cohorts. Patients were assessed for demographics, migraine‐related characteristics, treatment effectiveness (monthly migraine days [MMD] and/or monthly headache days [MHD]), and safety outcomes. The main outcome was the effectiveness measured by ≥50% response rate in MMD between the two groups. Secondary outcomes included other effectiveness measurements regarding the number of MMD and MHD and treatment emerging adverse events. Results: A total of 388 patients with migraine under anti‐CGRP treatments (194 with autoimmune diseases and 194 age‐ and sex‐matched controls without autoimmune diseases) were included. The proportion of patients achieving a ≥50% response rate in MMD was higher in patients without autoimmune diseases at 6 (69% vs. 53%; p = 0.006) and 9 months (74% vs. 52%; p = 0.006). Treatment emerging adverse events were comparable between the two groups (35% vs. 38%; p = 0.575). Patients with autoimmune disease had a significantly lower likelihood of achieving a ≥50% response in MMD compared with those without autoimmune disease (adjusted odds ratio, 0.61; 95% confidence interval, 0.44–0.85; p = 0.006), independent of comorbid depression and medication overuse. Conclusions: Our study shows that anti‐CGRP treatments are effective and safe for patients with migraine regardless the presence of autoimmune diseases, although an increased treatment response in patient without autoimmune disorders compared to patients with autoimmune disorders was observed. These findings highlight the need for early intervention, tailored strategies, and vigilant monitoring in patients with migraine and autoimmune disorders. Further research should explore immunomodulatory approaches to enhance outcomes. image