New daily persistent headache: A systematic review and meta-analysis.

OBJECTIVE: To perform a systematic review and meta-analysis of the epidemiology, precipitants, phenotype, comorbidities, pathophysiology, treatment, and prognosis of primary new daily persistent headache. METHODS: We searched PubMed/Medline, EMBASE, Cochrane, and clinicaltrials.gov until 31 December 2022. We included original research studies with any design with at least five participants with new daily persistent headache. We assessed risk of bias using National Institutes of Health Quality Assessment Tools. We used random-effects meta-analysis where suitable to calculate pooled estimates of proportions. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis compliant study is registered with PROSPERO (registration number CRD42022383561). RESULTS: Forty-six studies met inclusion criteria, predominantly case series, including 2155 patients. In 67% (95% CI 57-77) of cases new daily persistent headache has a chronic migraine phenotype, however new daily persistent headache has been found to be less likely than chronic migraine to be associated with a family history of headache, have fewer associated migrainous symptoms, be less vulnerable to medication overuse, and respond less well to injectable and neuromodulatory treatments. CONCLUSIONS: New daily persistent headache is a well described, recognisable disorder, which requires further research into its pathophysiology and treatment. There is a lack of high-quality evidence and, until this exists, we recommend continuing to consider new daily persistent headache a distinct disorder.

Calcitonin gene related peptide in migraine: current therapeutics, future implications and potential off-target effects.

Migraine is the second largest cause of years lost to disability globally among all diseases, with a worldwide prevalence over 1 billion. Despite the global burden of migraine, few classes of therapeutics have been specifically developed to combat migraine. After 30 years of translational research, calcitonin gene-related peptide (CGRP) inhibitors have emerged as a promising new tool in the prevention of migraine. Like all new therapeutics; however, we have limited real-world experience and CGRP has several known systemic actions that warrant consideration. This article provides a narrative review of the evidence for CGRP antagonists and summarises the known and potential side effects that should be considered.

Twelve-month efficacy of CGRP monoclonal antibodies and predictive value of short-term response: results of an Australian multicentre study.

Introduction: Clinical trials show that calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) are effective preventative treatments for chronic migraine. Their efficacy over longer time periods and in cohorts originally excluded from trials remains uncertain. This study aims to explore the impact of CGRP mAbs in an Australian real-life setting. Methods: A multicentre cohort study was performed in the tertiary headache clinics of the Alfred and Austin Hospitals, Melbourne, Australia. Patients were commenced on a CGRP mAb for chronic migraine and asked to keep a headache diary, recorded at 3 monthly appointments for 12 months. Primary outcome was a ≥50% reduction in monthly headache days (MHD). Results: From a population of 105 patients, 90 patients commenced galcanezumab and 15 commenced fremanezumab. The ≥50% responder rate of the cohort was 52.4% after 3 months. Over 12 months follow-up, 25.7% of the cohort ceased due to a lack of efficacy and 16.2% ceased due to an adverse event. There was no difference in response or cessation between medications. There was poor agreement in 3-month and 12-month response rates (Cohen's κ=0.130; p=0.171). On subgroup analysis, continuous headache at baseline and number of trialled preventative treatments were the only factors associated with efficacy. Conclusion: CGRP mAbs were associated with sustained reductions in MHD over 12-month follow-up in patients with resistant migraine in Australia. Further studies are required to determine treatment options for patients with continuous headache. Poor agreement between outcomes at 3 and 12 months highlights the need to assess some patients at later timepoints.

Status migrainosus inpatient treatment with eptinezumab (SMITE): study protocol for a randomised controlled trial.

INTRODUCTION: Status migrainosus is a disabling complication of migraine, which frequently results in hospitalisation. For patients who fail to respond to simple analgesia, triptans and intravenous prochlorperazine or chlorpromazine, there are limited treatment options, and a paucity of high-quality evidence to guide clinical practice. Eptinezumab, an intravenous monoclonal antibody specific for the calcitonin gene-related peptide ligand which achieves maximal plasma concentration immediately following administration and may improve migraines from day one. Intravenous lignocaine is an anaesthetic medication used in treatment of status migrainosus, often requiring prolonged admissions and with potential cardiac adverse events. The aim of this study is to assess the efficacy and safety of eptinezumab in the treatment of status migrainosus in comparison to intravenous lidocaine. METHODS AND ANALYSIS: Status migrainosus inpatient treatment with eptinezumab is a randomised, controlled, single-centre clinical trial conducted in a parallel design with an active comparator conducted in Melbourne, Australia. This study randomises forty patients (1:1) to receive either eptinezumab or an infusion of intravenous lignocaine for up to 5 days. It will assess the effect of eptinezumab compared with intravenous lignocaine in aborting status migrainosus, with the primary outcome of time from infusion until resolution of pain. It will explore several secondary measures including change in health resource utilisation, effect on patient reported outcomes of migraine disability and the safety and tolerability of each medication. ETHICS AND DISSEMINATION: This study has been reviewed and approved by the Human Research Ethics Committee of Alfred Health, local reference number 443/21, and all participants will provide informed consent for participation in the trial and dissemination of results. TRIAL REGISTRATION NUMBER: The trial registration number is ACTRN12621001616864. The results of this study will be disseminated through peer-reviewed journals, conference presentations and social media.