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Atogepant for the Prevention of Episodic Migraine in Adults: A Systematic Review and Meta-Analysis of Efficacy and Safety.
Full text linkINTRODUCTION
The inhibition of the calcitonin gene-related peptide (CGRP) pathway has attracted interest in pharmacological research on migraine. Atogepant is a potent, selective, orally available antagonist of the CGRP receptor approved as a preventive treatment of episodic migraine. This systematic review with meta-analysis aims to evaluate the efficacy and safety of atogepant for the prevention of episodic migraine in adult patients.
METHODS
Randomized, placebo-controlled, single or double-blinded trials were identified through a systematic literature search (December week 4, 2021). Main outcomes included the changes from baseline in monthly migraine days and the incidence of adverse events (AEs) and treatment withdrawal due to AEs. Mean difference (MD) and risk ratio (RR) with 95% confidence intervals (95% CIs) were estimated.
RESULTS
Two trials were included, overall enrolling 1550 patients. A total of 408 participants were randomized to placebo, 314 to atogepant 10 mg, 411 to atogepant 30 mg, and 417 to atogepant 60 mg once daily. The mean age of the patients was 41.0 years and 87.7% were women. The reduction in the mean number of migraine days from baseline across the 12-week treatment period was significantly greater among patients treated with atogepant at either the daily dose of 10 mg (MD - 1.16, 95% CI - 1.60 to - 0.73, p < 0.001), 30 mg (MD - 1.15, 95% CI - 1.54 to - 0.76, p < 0.001), or 60 mg (MD - 1.20, 95% CI - 2.18 to - 0.22, p = 0.016) than with placebo. There were no differences in the occurrence of AEs and drug withdrawal due to AEs between atogepant and placebo groups. Constipation was more commonly observed in patients treated with atogepant at 30 mg/day than placebo (RR 5.19, 95% CI 2.00-13.46; p = 0.001). Treatment with atogepant at the daily dose of 60 mg was associated with a higher risk of constipation (RR 4.92, 95% CI 1.89-12.79; p = 0.001) and nausea (RR 2.73, 95% CI 1.47-5.06; p = 0.001) than placebo.
CONCLUSION
Atogepant is an efficacious and overall well-tolerated treatment for the prevention of episodic migraine in adults
The evolving concept of multimorbidity and migraine
No full text: Migraine presents with high prevalence and similar clinical course with different disorders such as neurological, psychiatric, cardio- and cerebrovascular, gastrointestinal, metabolic-endocrine, and immunological conditions, which can often cooccur themselves. Multifaceted mechanisms subtend these comorbidities with a bidirectional link. First, a shared genetic load can explain the cooccurrence. Second, comorbid pathologies can promote disproportionate energetic needs, thalamocortical network dysexcitability, and systemic transient or persistent proinflammatory state, which may trigger the activation of a broad self-protective network that includes the trigeminovascular system in conjunction with the neuroendocrine hypothalamic system. This response results in maintenance of brain homeostasis by modulating subcortical-cortical excitability, energetic balance, osmoregulation, and emotional response. In this process, the CGRP is released in the trigeminovascular system. However, the calcitonin gene-related peptide (CGRP) plays several actions also outside the brain to maintain the homeostatic needs and is involved in the physiological functions of different systems, whose disorders are associated with migraine. This aspect further increases the complexity of migraine treatment, where standard therapies often have systemic adverse effects. On the other hand, some preventives can improve comorbid conditions. In summary, we propose that migraine management should involve a multidisciplinary approach to identify and mitigate potential risk factors and comorbidity and tailor therapies individually
Visit-to-visit variability in blood pressure and Alzheimer's disease
No full textAlzheimer's disease is the most common type of dementia and one of the leading sources of disability and dependency in the elderly. Given the limited treatment options, understanding the role of modifiable risk factors implied in the disease pathogenesis is a worthwhile endeavor to limit its global burden. Recently, the variability of blood pressure has been suggested to be a significant determinant of brain alterations and a potential therapeutic target. The aim of this article is to review the clinical evidence on the association between visit-to-visit blood pressure variability and Alzheimer's disease, highlight the underlying mechanisms, and suggest future implications
Vascular predictors of cognitive decline in patients with mild cognitive impairment
No full textOur aim in this study was to assess the relationship between the state of cerebral vessels and the risk of conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD). We included 117 MCI patients. They underwent an ultrasonographic assessment of common carotid arteries intima-media thickness (IMT) and carotid plaque index. Cerebrovascular reactivity to hypercapnia in the middle cerebral arteries was calculated with the Breath-Holding Index (BHI). After a 12-month follow-up period, neuropsychological examinations demonstrated a progression to dementia in 21 patients. Pathological values of BHI and IMT significantly increased the risk of conversion (BHI: odds ratio, 5.80; 95% confidence interval, 1.83-18.37, p < 0.05; IMT: odds ratio, 3.08; 95% confidence interval, 1.02-9.33; p < 0.05, multinomial logistic regression analysis). Comparison between patients with all normal values and those with the simultaneous alteration of the 2 vascular indexes showed an increase in the risk of conversion from 9% to 33% (ordinal regression analysis). Our findings show that alterations of cerebral vessel functional and anatomic status increase the risk of conversion from MCI to dementia. © 2012 IBRO
Psychopathological variables in chronic migraine patients with different therapeutic approach: psychological profile differences and impact on therapeutic efficacy in real life
No full textBackground: Migraine is a debilitating neurological condition linked to various psychological comorbidities. The aims of our study are: 1) to evaluate potential psychopathological differences between patients in treatment with anti-CGRP monoclonal antibodies (SPECIFIC group) and those with onabotulinumtoxin-A/oral pharmacotherapy (Group NON-SPECIFIC), 2) to compare treatment efficacy over time between groups, and examined whether psychopathological comorbidities can influence it. Methods: This is a post-hoc ambispective study: a retrospective analysis of patient-level real-life data prospectively collected for clinical evaluation. We enrolled 102 patients with chronic migraine (CM), 64 in treatment with erenumab or galcanezumab, and 38 with botulinum toxin or oral pharmacotherapies. Psychopathological variables are assessed at baseline, whereas clinical factors over time. Results: The NON-SPECIFIC group showed more pronounced emotion regulation difficulties (DERS, p = 0.001), alexithymia (TAS-20, p = 0.012), and impulsiveness (BIS-11, p = 0.002) with respect to the SPECIFIC group. Moreover, treatment efficacy overtime was more pronounced in the group with anti-CGRP treatment with a reduction of migraine frequency overtime, pain intensity, and improved quality of life up to six months post-treatment. Psychopathological comorbidity did not influence treatment efficacy. Conclusions: Our study highlighted more pronounced psychopathological comorbidities in patients in treatment with NON-SPECIFIC therapies in terms of impulsivity, alexithymia, and emotion regulation. Moreover, treatment efficacy overtime was more pronounced and stable over time in the SPECIFIC group, and psychopathological comorbidity did not influence it
Impact of carotid stenosis on the outcome of stroke patients submitted to reperfusion treatments: a narrative review
No full textIntravenous thrombolysis (IT) and mechanical thrombectomy (MD) are the two interventional approaches that have changed the outcome of patients with acute ischemic stroke (AIS). Ipsilateral and contralateral carotid stenosis (ICS, CCS) play an important role in regulating cerebral hemodynamics, both in chronic and acute situations such as AIS. Several studies have explored their role in the incidence and severity of stroke, but very few have investigated the possible impact of ICS and CCS on the efficacy of interventional procedures. The purpose of this review was to I) highlight the incidence and prevalence of carotid stenosis (CS); II) assess the impact of ICS and CCS on cerebral hemodynamics; III) evaluate the effect of carotid stenosis on the efficacy of interventional therapies (IT and MT) for AIS; and IV) report therapeutic complications related to CS. We searched PubMed/Medline for case reports, reviews, and original research articles on English-language review topics during the period from January 1, 2000 to October 1, 2023. CS is associated with 15-20 % of the total number of AIS. ICS and CCS had a negative influence on both cerebral hemodynamics before AIS and outcome after interventional procedures (IT, MT alone or in bridging). Available data on cerebral hemodynamics and efficacy of interventional therapies for AIS suggest a negative role of CS. Therefore, early diagnosis of CS may be considered relevant to preventive and post-stroke treatment strategies
Acute carotid dissection in an adult caused by pertussis
No full textWe present a 57-year-old man who worked in a pediatric setting who, after a strong coughing attack caused by a pertussis infection, presented with an internal carotid dissection and a consequent ischemic cerebral lesion. This case suggests the importance of vaccination for subjects who belong to high-risk categories. © 2013 Elsevier B.V. All rights reserved
EMERGING RISK FACTORS FOR DEMENTIA: THE ROLE OF BLOOD PRESSURE VARIABILITY
No full textIn recent years, classical vascular risk factors have been suggested to play a role also in the development of degenerative dementia. Arterial hypertension has been implicated in the pathogenesis of dementia but no conclusive results have been produced yet; more recently, blood pressure variability (BPV) has been suggested as a more important risk factor for both silent brain vascular lesions and the development of dementia. Blood pressure variability is defined as the variation in blood pressure (BP) over time, measured on different time spans and in different ways. We reviewed current scientific literature about the role of BPV in the pathogenesis of dementia, and about the association of abnormal BPV patterns and different forms of dementia. We also suggested some hypothetical pathogenic mechanisms
Erenumab for preventive treatment of migraine: a systematic review and meta-analysis of efficacy and safety
No full textBACKGROUND: Novel therapeutic options with improved efficacy and safety profiles are needed for the prophylaxis of migraine. In recent years, the inhibition of calcitonin gene-related peptide (CGRP) signaling has attracted growing interest in the pharmacological research on migraine. Erenumab is the first fully human monoclonal antibody directed against the CGRP receptor to be approved for use in migraineurs. OBJECTIVE: To evaluate the efficacy and safety of erenumab as preventive treatment in patients with migraine using meta-analytical techniques. METHODS: Randomized, placebo-controlled, single- or double-blinded trials were identified through a systematic literature search (October week 4, 2018). Main outcomes included the changes from baseline in monthly migraine days (MMD) and monthly acute migraine-specific medication days (MSMD) at week 12, and the incidence of adverse events (AEs), severe AEs (SAEs) and treatment withdrawal due to AEs. Mean difference (MD) and risk ratio (RR) with 95% confidence intervals (95% CIs) were estimated. RESULTS: Across the five included trials, erenumab given as a subcutaneous injection at a monthly dosage of 70 mg and 140 mg was associated with a significantly greater reduction in baseline MMD (70 mg: MD - 1.3, 95% CI - 1.7 to - 1.0, p < 0.001; 140 mg: MD - 1.9, 95% CI - 2.3 to - 1.4, p < 0.001) and MSMD (70 mg: MD - 1.0, 95% CI - 1.6 to - 0.4, p < 0.001; 140 mg: MD - 1.8, 95% CI - 2.5 to - 1.1, p < 0.001) than placebo. There were no differences in the occurrence of AEs, SAEs, and drug withdrawal due to AEs between the erenumab and placebo groups. CONCLUSIONS: Erenumab is an efficacious and well tolerated preventive treatment in adult patients with episodic and chronic migraine
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