Safety of Onabotulinumtoxin A in Chronic Migraine: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Some 14% of global prevalence, based on high-income country populations, suffers from migraine. Chronic migraine is very disabling, being characterized by at least 15 headache days per month of which at least 8 days present the features of migraine. Onabotulinumtoxin A, targeting the machinery for exocytosis of neurotransmitters and neuropeptides, has been approved for use in chronic migraine since 2010. This systematic review and meta-analysis appraises the safety of onabotulinumtoxin A treatment for chronic migraine and the occurrence of treatment-related adverse events (TRAEs) in randomized, clinical studies in comparison with placebo or other comparators and preventative treatments according to the most updated Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 recommendations. The search retrieved 888 total records. Nine studies are included and seven were eligible for meta-analysis. The present study demonstrates that toxin produces more TRAEs than placebo, but less than oral topiramate, supporting the safety of onabotulinumtoxin A, and highlights the heterogeneity of the studies present in the literature (I2 = 96%; p < 0.00001). This points to the need for further, adequately powered, randomized clinical trials assessing the safety of onabotulinumtoxin A in combination with the newest treatment options.

Focus on zavegepant: the first intranasal third-generation gepant.

Migraine is the leading cause of years lived with disability in people under 50 and its burden is increased by calcitonin gene-related peptide (CGRP)-driven chronicity. Newly approved small molecules that antagonize the CGRP receptor, gepants, have advanced from the hepatotoxic first-generation telcagepant to third-generation intranasal zavegepant; during this process of drug development, rimegepant, ubrogepant and atogepant, which are orally administered, have been launched and approved for clinical use with no warning for hepatotoxicity. Real-world, long-term postmarketing data about the efficacy and safety of gepants are awaited. The aim of the present drug evaluation study was to provide an overview of the novel, third-generation intranasal zavegepant, encompassing its development and future perspectives.

Migraine is the leading cause of years lived with disability in people under 50 and the frequent chronicity of the disease increases its global burden. Recent research prompted the discovery of novel modulators fundamentally involved in the pathogenesis and chronicity of migraine, such as calcitonin gene-related peptide (CGRP). This induced the development of new drugs able to antagonize the CGRP receptor, called gepants. The purpose of the present study was to offer a monograph on the novel, third-generation gepant, zavegepant. It is the first gepant to be administered via the intranasal route. Here, the authors report the available data on the efficacy and safety of zavegepant and investigate future perspectives.

Pooled Analysis of Real-World Evidence Supports Anti-CGRP mAbs and OnabotulinumtoxinA Combined Trial in Chronic Migraine.

OnabotulinumtoxinA, targeting the CGRP machinery, has been approved for the last two decades for chronic migraine prevention. The recently approved monoclonal antibodies (mAbs) directed towards the calcitonin gene-related peptide (CGRP) pathway open a new age for chronic migraine control. However, some 40% patients suffering from chronic migraine is still resistant to treatment. The aim of this work is to answer the following PICOS (participants intervention comparator outcome study design) question: Is there evidence of efficacy and safety of the combined administration of anti-CGRP mAbs and onabotulinumtoxinA in chronic migraine? A systematic review and meta-analysis [Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 recommendations] was made up to 19 April 2022. The results are encouraging: the combined treatment proved to afford ≥50% monthly headache days (MHDs)/frequency reduction respect to baseline in up to 58.8% of patients; in comparison, anti-CGRP mAbs reduce MHDs of 1.94 days from baseline and botulinum toxin of 1.86 days. Our study demonstrates for the first time that the combination therapy of onabotulinumtoxinA with anti-CGRP mAbs affords a reduction of 2.67 MHDs with respect to onabotulinumtoxinA alone, with moderate certainty of evidence. Adequately powered, good-quality studies are needed to confirm the response to combination therapy in terms of efficacy and safety. PROSPERO registration: CRD42022313640.

Anticholinergic Burden is Associated With Increased Mortality in Older Patients With Dependency Discharged From Hospital.

OBJECTIVES: To determine whether anticholinergic burden may predict differently 1-year mortality in older patients discharged from acute care hospitals with or without dependency in basic activities of daily living (BADL). DESIGN: Prospective observational study. SETTING AND PARTICIPANTS: Our series consisted of 807 patients aged 65 years or older consecutively discharged from 7 acute care geriatric wards throughout Italy between June 2010 and May 2011. MEASURES: Overall anticholinergic burden was assessed by the anticholinergic cognitive burden (ACB) score. Dependency was rated by BADL, and dependency in at least 1 BADL was considered as a potential mediator in the analysis. The study outcome was all-cause mortality during 12-months of follow-up. RESULTS: Patients included in the study were aged 81.0 ± 7.4 years, and 438 (54.3%) were female. During the follow-up period, 177 out of 807 participants (21.9%) died. After adjusting for potential confounders, discharge ACB score = 2 or more was significantly associated with the outcome among patients with dependency in at least 1 BADL [hazard ratio (HR) 2.25 95% confidence (CI) 1.22‒4.14], but not among independent ones (HR 1.06 95% CI 0.50‒2.34). The association was confirmed among dependent patients after adjusting for the number of lost BADL at discharge (HR 2.20 95% CI 1.18‒4.04) or ACB score at 3-month follow-up (HR 2.18 95% CI 1.20‒3.98), as well as when considering ACB score as a continuous variable (HR 1.28 95% CI 1.11‒1.49). The interaction between ACB score at discharge and BADL dependency was highly significant (P < .001). CONCLUSIONS/IMPLICATIONS: ACB score at discharge may predict mortality among older patients discharged from an acute care hospital carrying at least 1 BADL dependency. Hospital physicians should be aware that prescribing anticholinergic medications in this population may have negative prognostic implications and they should try to reduce anticholinergic burden at discharge whenever possible.