Acute Treatment Of Migraine Research Articles

Safety of Rimegepant in Adults with Migraine and Anxiety, Depression, or Using Antidepressants: Analysis of a Multicenter, Long-Term, Open-Label Study.

Anxiety and depression are frequently associated with migraine, and antidepressant use can complicate treatment. These analyses assessed the safety and tolerability of rimegepant in participants with migraine and anxiety and/or depression, or using selective serotonin reuptake inhibitors (SSRIs) and/or other antidepressants. Data were from a phase II/III safety study of rimegepant for the acute treatment of migraine. Participants with a history of 2-14 migraine attacks per month of moderate or severe pain intensity self-administered rimegepant 75mg as needed up to once daily for up to 52weeks. These post hoc subgroup analyses assessed safety according to self-reported history of anxiety (yes or no) or depression (yes or no), and current use of SSRIs (yes or no) or other antidepressants (yes or no). Of 1800 treated participants, 23.2% (n = 417) had a self-reported history of anxiety, 23.7% (n = 426) had a self-reported history of depression, and 11.2% (n = 202) reported both anxiety and depression. A total of 10.1% (n = 181) of participants were using an SSRI, 10.8% (n = 195) were using other antidepressants, and 1.8% (n = 32) were using both. Across the subgroups with anxiety, without anxiety, with depression, without depression, using SSRIs, not using SSRIs, using other antidepressants, and not using other antidepressants, respectively, similar proportions of participants reported adverse events (67.1%, 58.4%, 62.0%, 60.0%, 64.1%, 60.0%, 66.2%, 59.8%), serious adverse events (3.6%, 2.3%, 2.8%, 2.5%, 3.3%, 2.5%, 5.1%, 2.3%), and discontinuation of rimegepant due to adverse events (4.1%, 2.2%, 3.1%, 2.5%, 5.0%, 2.4%, 3.1%, 2.6%). Numerical improvements in a variety of participant-reported outcomes were also observed at weeks 12 and 52. Rimegepant showed favorable safety and tolerability in adults with migraine and a history of anxiety and/or depression and with SSRI and/or other antidepressant use. Clinicaltrials.gov: NCT03266588.

Efficacy of lasmiditan, rimegepant and ubrogepant for acute treatment of migraine in triptan insufficient responders: systematic review and network meta-analysis

BackgroundNovel abortive treatments for migraine, ditans and gepants, have promising implications in triptan-insufficient responders with minimal existing comparative data. Our study aims to synthesize evidence through a systematic review and network meta-analysis to assess the comparative efficacy of lasmiditan, rimegepant and ubrogepant in triptan-insufficient responders.MethodWe searched PubMed, Embase, CENTRAL, and EBSCO Open Dissertations up to May 2024. We included randomized controlled trials (RCTs) that compared novel abortive treatments, including lasmiditan, rimegepant, and ubrogepant, in migraine patients who self-reported insufficient response to triptans. Outcomes are represented using relative risks with corresponding 95% confidence intervals (CI). The surface under the cumulative ranking curve (SUCRA) was used to rank each medication.ResultsA total of five phase 3 RCTs involving 3,004 patients were included in the analysis. All three agents were significantly superior to placebo for two-hour pain freedom (RR = 1.93, 95% CI [1.52, 2.46]), freedom from the most bothersome symptoms at two hours (RR = 1.55, 95% CI [1.37, 1.75]), and pain relief at two hours (RR = 1.46, 95% CI [1.35, 1.58]). No statistically significant differences in efficacy outcomes were observed among the three agents. However, lasmiditan 200 mg had the highest cumulative probability for two-hour pain freedom and relief (SUCRA 0.9, 0.8, respective), while rimegepant led in relieving the most bothersome symptoms (SUCRA 0.7).ConclusionLasmiditan, rimegepant, and ubrogepant are effective for acute treatment of migraine in triptan-insufficient responders, with high-dose lasmiditan showing the highest efficacy for pain control.

Effects of multiple-dose administration of zavegepant nasal spray on the single-dose pharmacokinetics of ethinyl estradiol-levonorgestrel.

The potential for drug-drug interaction of multiple-dose intranasal zavegepant on the single-dose oral contraceptive ethinyl estradiol and levonorgestrel (EE-LNG) was evaluated. Zavegepant (as a nasal spray) is a calcitonin gene-related peptide receptor antagonist approved in the United States for treatment of acute migraine in adults. This single-center, Phase 1, open-label, fixed-sequence study included healthy, nonsmoking females (18-45 years old). In treatment Period 1, a single oral dose of EE-LNG 0.02-0.10 mg was administered on Day 1. In treatment Period 2, intranasal zavegepant (20 mg daily; 10 mg per nostril separated by 1 h) was administered on Days 1-5; 1 oral dose of EE-LNG 0.02-0.10 mg was administered immediately after first 10 mg intranasal zavegepant dose on Day 2. Blood samples for EE-LNG concentrations were collected on Day 1, treatment Period 1, and Day 2, treatment Period 2, and zavegepant concentrations on Day 2, treatment Period 2. Noncompartmental pharmacokinetic parameters included maximum observed concentration (Cmax), area under the concentration-time curve (AUC) from Time 0 to last non-zero concentration (AUC0-t), and AUC from Time 0 to infinity (AUC0-inf). The safety and pharmacokinetic sample sizes were 26 and 23, respectively. Statistical comparisons of pharmacokinetic exposure parameters after co-administration of zavegepant and EE-LNG versus EE-LNG alone showed small, but statistically insignificant, changes in either EE or LNG exposure. EE comparison ratios (90% confidence intervals [CIs]) were 109.9% (105.3%, 114.8%) for AUC0-inf and 110.2% (104.6%, 116.1%) for Cmax. LNG comparison ratios (90% CIs) were 107.0% (100.2%, 114.3%) for AUC0-inf and 108.8% (99.9%, 118.4%) for Cmax. Frequently reported treatment-emergent adverse events included dysgeusia (n = 25, 96%), throat irritation (n = 11, 42%), headache (n = 10, 39%), nasal discomfort (n = 7, 27%), pharyngeal paresthesia (n = 5, 19%), and nausea (n = 4, 15%). Co-administration of zavegepant nasal spray with a single dose of an oral contraceptive resulted in no clinically meaningful changes (<12% increase) in EE-LNG exposure.

Population pharmacokinetic modeling of zavegepant, a calcitonin gene-related peptide receptor antagonist, in healthy adults and patients with migraine.

Zavegepant (ZAVZPRET™) is a high-affinity, selective, small-molecule calcitonin gene-related peptide receptor antagonist available for acute treatment of migraine in adults. A population pharmacokinetic analysis was performed to describe zavegepant plasma concentration-time course, characterize bioavailability, and identify covariates affecting zavegepant exposure. The model was developed and validated using data from 10 phase I clinical studies, wherein zavegepant was administered intravenously, intranasally, or orally to healthy adults and patients with migraine. Plasma concentration-time data were analyzed using nonlinear mixed-effects modeling. A three-compartment model with first-order elimination from the central compartment, and sequential zero- and first-order absorption best described the observed plasma concentration-time course of zavegepant. Bioavailability was 5.1% and 0.65% for intranasal and oral treatment, respectively; absorption rate constants were 5.8 and 0.8 h-1, respectively. Body weight-based empirical allometric scaling was applied using standard exponents (0.75 for clearance and 1 for volume of distribution). Age (range 18-71 years), race, ethnicity, sex, renal function, and co-administration of oral contraceptives or sumatriptan did not significantly change zavegepant pharmacokinetics. Moderate hepatic impairment (Child-Pugh score 7-9) or co-administration of rifampin decreased elimination clearance of oral zavegepant by ~40%. The zavegepant population pharmacokinetic model adequately characterized zavegepant concentration-time profiles, the bioavailability of intranasal and oral zavegepant, as well as the effect of intrinsic and extrinsic factors on zavegepant pharmacokinetics.

The potential to prevent unnecessary emergency department visits by timely diagnosis of migraine-A prospective observational study.

Successful acute migraine treatment potentially prevents emergency room (ER) consultations but requires that the diagnosis of migraine was given earlier. The aim of this study is to quantify the problem of missed migraine diagnosis prior to ER visits. Inclusion criterion for this single-center prospective study was the presentation at the ER for acute headache. Patients with acute migraine attacks were assessed for previous migraine attacks, and whether they were given a diagnosis of migraine in the past. Of 137 patients with migraine diagnosis at discharge, 108 (79%) had previous headache attacks fulfilling the criteria for migraine according to The International Classification of Headache Disorders 3rd edition (ICHD-3). Of those, 54 (50%) received the diagnosis for the first time. Half of the migraine patients (50%) presenting in the ER for headache could have been diagnosed earlier. This highlights the need for better detection and treatment of migraine by pre-hospital healthcare providers, as earlier diagnosis and specific acute treatment could have prevented the ER visit.

Long-Term (12-Month) Safety and Tolerability of STS101 (Dihydroergotamine Nasal Powder) in the Acute Treatment of Migraine: Data from the Phase 3 Open-Label ASCEND Study.

STS101 is an investigational drug-device combination comprising 5.2 mg dihydroergotamine (DHE) powder (6.0 mg DHE mesylate) in a single-use nasal delivery device for the acute treatment of migraine. The primary objective of the ASCEND trial was to assess long-term safety and tolerability of STS101 in the acute treatment of migraine attacks across 12-18 months, with secondary objectives describing efficacy. ASCEND was an open-label study of STS101 in adults aged 18-65 years with a ≥ 1 year history of migraine with or without aura, with onset before the age of 50 years and 4-12 migraine attacks/month and < 15 headache days/month in each of the 3 months prior to screening. Exclusion criteria included diagnosis of non-migraine headache, history of cerebrovascular disease, and ≥ 2 cardiovascular risk factors. After establishing eligibility, participants could self-administer STS101 5.2 mg as needed for up to 2 doses within 24 h to treat a single migraine attack and up to 12 doses/month. Safety and tolerability evaluations included physical and nasal examinations, vital signs, laboratory tests, and treatment-emergent adverse event (TEAE) assessments. Participants used an electronic diary to record exploratory efficacy parameters, including intensity of headache pain and associated migraine symptoms (photophobia, phonophobia, and nausea). Participant impression questions were asked at months 3, 6, and 12. Of the 6610 migraine attacks treated with a total of 8234 STS101 doses in 344 participants, 945/6610 (14.3%) were associated with a TEAE. Events were predominantly mild or moderate in nature and rarely led to premature study discontinuation (15/344 [4.4%] participants). Treatment was associated with rapid onset of freedom from pain (36.6%, 67.1%, and 85.5% of treated attacks 2, 4, and 24 h post-dose, respectively), freedom from most bothersome symptoms (54.3%, 79.6%, and 91.3%), and headache relief (66.5%, 89.1%, and 94.3%). Most participants rated treatment results as good or very good and ease of use as easy or very easy at all time points (months 3, 6, and 12) and indicated they were likely or very likely to use STS101 again. The repeated long-term, as-needed use of STS101 was well tolerated, demonstrating a favorable safety profile in the acute treatment of migraine attacks in appropriately indicated adults. Exploratory efficacy evaluations indicated beneficial effects, which warrant further evaluation. ClinicalTrials.gov identification NCT04406649.

Evaluation of rimegepant utilization patterns and patient characteristics among new users: a United States administrative claims-based study

Objective To assess tablet utilization patterns and describe pre-treatment characteristics among new users of rimegepant. Background Rimegepant is the only oral calcitonin gene-related peptide antagonist approved in the United States for both the acute and preventive treatment of migraine. Methods We conducted a retrospective cohort study of people with migraine who initiated treatment with rimegepant using two US commercial claims databases (MarketScan and Optum). Patients (≥18 years old) with migraine who newly initiated rimegepant were included. Patients were stratified into two groups representing acute (quantity = 8) and prevention (quantity = 15 or 16) use cohorts. Baseline characteristics and medication use history were assessed on index and during the 365-day pre-index period. Rimegepant utilization periods were calculated based on days supplied and varying approaches to define use periods. Tablet quantity per 30 days was reported separately for both acute and prevention cohorts. Results In MarketScan, a total of 14,037 rimegepant users were identified; 11,195 (79.8%) in the acute group and 1,880 (13.4%) in the prevention group. Rimegepant utilization for acute use was 4.9 ± 2.1 tablets per 30 days and for preventive use was 13.1 ± 7.7 tablets per 30 days. There was high baseline prevalence of triptan contraindications, warnings, and high cardiovascular risk, with a combined 46.2% meeting one or more of these criteria. Acute medication overuse was also common (25.1%) prior to rimegepant initiation. Results were consistent in the Optum database. Conclusion Our analysis provides the first real-world data available on tablet utilization and characteristics of new users of rimegepant.

Enhancing Acute Migraine Treatment: Exploring Solid Lipid Nanoparticles and Nanostructured Lipid Carriers for the Nose-to-Brain Route.

Migraine has a high prevalence worldwide and is one of the main disabling neurological diseases in individuals under the age of 50. In general, treatment includes the use of oral analgesics or non-steroidal anti-inflammatory drugs (NSAIDs) for mild attacks, and, for moderate or severe attacks, triptans or 5-HT1B/1D receptor agonists. However, the administration of antimigraine drugs in conventional oral pharmaceutical dosage forms is a challenge, since many molecules have difficulty crossing the blood-brain barrier (BBB) to reach the brain, which leads to bioavailability problems. Efforts have been made to find alternative delivery systems and/or routes for antimigraine drugs. In vivo studies have shown that it is possible to administer drugs directly into the brain via the intranasal (IN) or the nose-to-brain route, thus avoiding the need for the molecules to cross the BBB. In this field, the use of lipid nanoparticles, in particular solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), has shown promising results, since they have several advantages for drugs administered via the IN route, including increased absorption and reduced enzymatic degradation, improving bioavailability. Furthermore, SLN and NLC are capable of co-encapsulating drugs, promoting their simultaneous delivery to the site of therapeutic action, which can be a promising approach for the acute migraine treatment. This review highlights the potential of using SLN and NLC to improve the treatment of acute migraine via the nose-to-brain route. First sections describe the pathophysiology and the currently available pharmacological treatment for acute migraine, followed by an outline of the mechanisms underlying the nose-to-brain route. Afterwards, the main features of SLN and NLC and the most recent in vivo studies investigating the use of these nanoparticles for the treatment of acute migraine are presented.

Characterization of rimegepant drug-drug interactions using the cytochrome P450 probe drugs, itraconazole, rifampin, fluconazole, and midazolam.

Reported here are the results of four rimegepant phase I studies, in healthy participants, aimed at determining the invivo potential of rimegepant (75 mg) for cytochrome P450 (CYP) 3A4-related drug-drug interactions (DDIs). Rimegepant orally disintegrating tablet (Pfizer Inc., New York, NY, USA) is a calcitonin gene-related peptide receptor antagonist approved for acute treatment of migraine and preventive treatment of episodic migraine. People with migraine commonly use multiple drug treatments, with the potential for DDIs. Each study was an open-label, single-arm, single-sequence, crossover study. Rimegepant was tested as a victim drug by separate co-administration of itraconazole (a strong CYP3A4 inhibitor and P-glycoprotein inhibitor) in Study 1, rifampin (a strong CYP3A4 inducer and moderate CYP2C9 inducer) in Study 2, and fluconazole (a strong CYP2C9 inhibitor and moderate CYP3A4 inhibitor) in Study 3, and as a perpetrator drug by co-administration with midazolam (a CYP3A4 substrate) in Study 4. Mean values of single-dose rimegepant maximum concentration (Cmax) and area under the curve from time 0 to infinity (AUC0-inf) increased with itraconazole co-administration (n = 22) by 1.42-fold (90% confidence interval [CI] 1.25-1.61) and by 4.14-fold (90% CI 3.87-4.44), respectively, and decreased with rifampin co-administration (n = 21) to 36% (90% CI 31.2-41.4%) and to 19% (90% CI 16.3-21.4%), respectively. Co-administration with fluconazole (n = 23) increased rimegepant mean AUC0-inf by 1.80-fold (90% CI 1.68-1.93), with no impact on Cmax (1.04-fold; 90% CI 0.94-1.15). Co-administration of rimegepant single dose (300 mg; n = 14) or multiple doses (150 mg/day; n = 14) increased the mean Cmax of midazolam by 1.38-fold (90% CI 1.13-1.67) and 1.53-fold (90% CI 1.32-1.78), respectively, and the AUC0-inf of midazolam by 1.86-fold (90% CI 1.58-2.19) and 1.91-fold (90% CI 1.63-2.25), respectively. Based on the magnitude of DDIs, these studies indicate the following: co-administration of rimegepant with a strong CYP3A4 inhibitor should be avoided; during co-administration with a moderate CYP3A4 inhibitor, another dose of rimegepant within 48 h should be avoided; co-administration of rimegepant with a strong or moderate CYP3A4 inducer should be avoided; CYP2C9 does not play a meaningful role in rimegepant metabolism; and there is no clinically meaningful CYP3A4 inhibition by rimegepant.

Assessment of pharmacokinetic and pharmacodynamic interactions between zavegepant and sumatriptan: A phase 1, randomized, placebo-controlled study in healthy adults.

To evaluate the pharmacodynamic (PD) and pharmacokinetic (PK) interactions between zavegepant and sumatriptan in healthy adults. Zavegepant is a high-affinity, selective, small-molecule calcitonin gene-related peptide receptor antagonist administered as a nasal spray approved in the United States for the acute treatment of migraine. Triptans, including sumatriptan, are a different class of drugs for acute migraine treatment and are associated with a risk of increased blood pressure (BP). Hence, it is important to study the drug-drug interactions between zavegepant and sumatriptan due to potential coadministration in clinical settings. This was a Phase 1, single-center, partially blind, randomized, placebo-controlled, single-arm study. Eligible participants were males aged ≥ 18 and ≤ 40 years or females aged ≥ 18 and ≤ 50 years. On Day 1, participants received sumatriptan 2 × 6 mg subcutaneous injections (1 h apart) and were then randomized (6:1 ratio) to receive zavegepant 2 × 10 mg nasal spray (1 in each nostril) or placebo on Days 2 and 3. On Day 4, zavegepant or placebo was coadministered with sumatriptan after the second sumatriptan injection. BP, PK, and safety were evaluated at pre-specified time points. Forty-two participants enrolled in the study received at least one dose of any treatment and were included in the safety analyses. Forty-one participants who completed the study were included in the BP and PK analyses. The mean (standard deviation) time-weighted average (TWA) of mean arterial pressure (MAP [sumatriptan+ zavegepant 87.2 (6.8) vs. sumatriptan 86.9 (6.0)]), diastolic BP (DBP [sumatriptan + zavegepant 72.3 (6.8) vs. sumatriptan 72.1 (6.2)]), and systolic BP (SBP [sumatriptan + zavegepant 116.8 (10.2) vs. sumatriptan 116.2 (8.6)]) did not change following zavegepant and sumatriptan coadministration on Day 4 compared to sumatriptan alone on Day 1. Statistical comparisons of the TWA of MAP, DBP, and SBP between sumatriptan and zavegepant coadministration and sumatriptan alone were similar; the differences observed were 0.04 mmHg for MAP (90% confidence interval [CI]: -0.69, 0.77 mmHg), 0.00 mmHg for DBP (90% CI: -0.76, 0.76 mmHg), and 0.33 mmHg for SBP (90% CI: -0.97, 1.63 mmHg). Sumatriptan PK after sumatriptan and zavegepant coadministration versus sumatriptan alone was similar; the comparison ratios were 102.5% (90% CI: 100.7%, 104.2%) for AUC0-inf and 104.1% (90% CI: 98.0%, 110.6%) for Cmax. A small difference in zavegepant PK exposure after sumatriptan and zavegepant coadministration versus zavegepant alone was not considered clinically relevant: the comparison ratios were 112.4% (90% CI: 103.4%, 122.3%) for AUC0-24 and 96.7% (90% CI: 88.9%, 105.2%) for Cmax. Overall, 90% (38/42) of participants experienced ≥ 1 treatment-emergent adverse event that was mild or moderate in severity. All treatments were generally safe and well tolerated. Coadministration of zavegepant with sumatriptan was safe and without PD or PK interactions in healthy adults.

A Discrete-Choice Experiment Assessing the Patient Preferences and Real-World Experiences of Patients with Migraine in Japan.

Migraine is a debilitating headache disorder with a high prevalence in Japan that imposes significant societal burden. Although the Japanese Clinical Practice Guideline for Headache Disorders 2021 recommends both acute and preventive migraine treatments, the usage of preventive treatments is still limited. Therefore, it is crucial to understand the treatment preferences of patients with migraine pertaining to both acute and preventive treatments. A mixed-methods study including a discrete choice experiment (DCE) was conducted with Japanese patients with migraine (10 for the qualitative interviews, and 400 for the DCE) who were recruited from the Rakuten Insight panel. The DCE presented hypothetical treatment options including oral acute, oral preventive, and injectable preventive medications. Six attributes (method of delivery, reduction of pain, impact of headaches on daily routines, dosage adjustability, and temporary and persistent side effects) each with three levels were included in the survey. A hierarchical Bayesian model was used to estimate relative attribute importance scores (RAI) for all attributes. For the 400 participants in the DCE, the most common age bracket was 40-49years old, and the majority were female (66.75%). RAI estimates indicated that "method of delivery" was the most important attribute for patients (RAI 51.92, SD = 10.20), followed by "reduction of pain when experiencing a headache" (RAI 17.00, SD = 7.74). Oral preventive treatments were preferred over injectable preventive treatments. The qualitative interviews showed that patients prefer oral medications to injectable treatments, and a lack of awareness regarding preventive treatments. This study found that the "method of delivery" was the most important driver of treatment preferences of patients with migraine in Japan, with oral acute medications being preferred. Oral preventive treatments were found to be preferred over injectable treatments. These results may indicate the need for increased education regarding preventive treatments, as well as the need for further development of these treatments.

Mass balance and pharmacokinetic characterization ofzavegepant in healthy male subjects.

Zavegepant, a high-affinity, selective, small-molecule calcitonin gene-related peptide receptor antagonist, is approved as a nasal spray for acute treatment of migraine in adults. This phase I, open-label, single-center, single-period, nonrandomized study in six healthy male subjects assessed mass balance recovery after a single 15-min intravenous (IV) infusion dose of carbon-14 ([14C])-zavegepant. Blood, urine, and fecal samples were collected over 192 h for analysis of zavegepant in plasma and urine; total radioactivity (TR) in plasma, whole blood, urine, and feces; and zavegepant metabolite profiling and structural identification in plasma, urine, and feces. An average of 96.6% of radioactivity administered was recovered in excreta. Most TR (mean 84.9%) was recovered in the feces, indicating that biliary/fecal elimination was the main route. Volume of distribution of zavegepant based on the terminal phase (129 L) was higher than total body water (42 L), indicating substantial distribution into tissue. Total plasma clearance of zavegepant (220 mL/min) is identical to whole blood clearance given the blood/plasma partition ratio of 1, lower than typical hepatic blood flow (1450 mL/min). The observed plasma terminal half-life of zavegepant was 6.8 h. Exposure to zavegepant accounted for ~90% of circulating plasma TR, suggesting that very low levels of uncharacterized circulating metabolites were present. Metabolite profiling did not identify any metabolites representing ≥10% of radioactivity in plasma, urine, or feces. A single IV infusion of 5 mg [14C]-zavegepant was well tolerated in healthy male subjects. Disposition findings of IV [14C]-zavegepant are applicable to the disposition of the approved zavegepant nasal spray.

First real-world study on the effectiveness and tolerability of rimegepant for acute migraine therapy in Chinese patients

BackgroundRimegepant, a small molecule calcitonin gene-related peptide (CGRP) receptor antagonist, is indicated for acute and preventive migraine treatment in the United States and other countries. However, there is a lack of prospective real-world evidence for the use of rimegepant in Chinese migraine patients.MethodsThis was a single-arm, prospective, real-world study. While taking rimegepant to treat migraine attacks as needed, eligible participants were asked to record their pain intensity, functional ability, and accompanying symptoms for a single attack at predose and 0.5, 1, 2, 24, and 48 h postdose via a digital platform. Adverse events (AEs) during the rimegepant treatment period were recorded and analysed. The percentages of participants who experienced moderate to severe pain at predose and 0.5, 1, 2, 24, and 48 h postdose were assessed. Additionally, the percentages of participants who reported better/good outcomes in terms of pain intensity, functional ability, and accompanying symptoms at 0.5, 1, 2, 24, and 48 h postdose were analysed. In addition, the total cohort (full population, FP) was stratified into a prior nonresponder (PNR) group to observe the effectiveness and safety of rimegepant for relatively refractory migraine and a rimegepant and eptinezumab (RE) group to observe the effectiveness and safety of the combination of these drugs.ResultsBy November 24th, 2023, 133 participants (FP, n = 133; PNR group, n = 40; RE group, n = 28) were enrolled, and 99 participants (FP, n = 99; PNR group, n = 30; RE group, n = 23) were included in the analysis. Rimegepant was effective in treating migraine in the FP and both subgroups, with a significant decreasing trend in the percentages of participants experiencing moderate to severe pain postdose (p < 0.05) and a marked increase in the percentages of participants who reported better/good outcomes in terms of pain intensity, functional ability, and accompanying symptoms at 0.5, 1, 2, 24, and 48 h postdose compared with predose. AEs were reported by 6% of participants in the FP, and all AEs were mild.ConclusionsIn the real world, rimegepant is effective in the acute treatment of migraine patients in China. The low incidence rate of AEs highlighted the favourable tolerability profile of rimegepant.Trial registrationClinicaltrials.gov NCT05709106. Retrospectively registered on 2023-02-01.Graphical

Ubrogepant users' real-world experience: Patients on ubrogepant, characteristics and outcomes (UNIVERSE) study.

To assess the real-world effectiveness of ubrogepant by evaluating self-reported satisfaction with pain relief, ability to think clearly, and return to normal function in individuals who had used ubrogepant to treat a migraine episode within the preceding 14 days. Ubrogepant is an oral calcitonin gene-related peptide receptor antagonist approved for the acute treatment of migraine in adults. Few studies have evaluated the real-world effectiveness of ubrogepant. The UNIVERSE study was an observational, cross-sectional survey conducted between February 2021 and April 2021 in US adult Migraine Buddy application (app) users currently treated with ubrogepant. Individuals who were 18 years of age or older and reported at least one dose of ubrogepant in the previous 14 days completed a 30-question survey in the app. The survey assessed respondent demographics, migraine history, acute treatment patterns, and treatment satisfaction with ubrogepant. Respondents also reported prior acute medication use and reasons for switching to ubrogepant. Of the 1303 ubrogepant users contacted, 302 (23.2%; 50 mg, 120 participants; 100 mg, 182 participants) were included in this study. The mean (standard deviation) age was 41.9 (11.2) years, and 90.1% (272/302) were female. Satisfaction with migraine relief at 2, 4, and 24 h post-dose was reported by 75.8% (229/302), 83.4% (252/302), and 78.5% (237/302) of participants, respectively. Satisfaction with the ability to think clearly after taking ubrogepant was reported by 85.1% (257/302) of participants, and 83.8% (253/302) were satisfied with their ability to return to normal function. Furthermore, 90.7% (274/302) of participants reported that they were likely to continue using ubrogepant to treat their migraine. Most participants (n = 264 [87%]) reported switching to ubrogepant due to inadequate treatment response with their previous treatment. In this subgroup, comparable outcomes were observed with respect to satisfaction with migraine relief, ability to think clearly, and return to normal function. Ubrogepant demonstrated real-world effectiveness in the acute treatment of migraine, as evidenced by high levels of treatment satisfaction and a strong indication of their intent to continue using the medication.

Effect of Ubrogepant on Patient-Reported Outcomes When Administered During the Migraine Prodrome: Results From the Randomized PRODROME Trial.

Ubrogepant is a calcitonin gene-related peptide receptor antagonist approved for the acute treatment of migraine. The PRODROME trial previously demonstrated that ubrogepant treatment during prodrome prevents the onset of moderate or severe headache. In this analysis of the PRODROME trial, the benefits of ubrogepant treatment during the prodrome on patient-reported outcomes (PROs) are evaluated. PRODROME was a multicenter, randomized, double-blind, placebo-controlled, crossover trial that enrolled adults who experienced 2-8 migraine attacks per month with moderate-severe headache pain. Eligible participants treated 2 qualifying prodrome events, defined as a migraine attack with prodromal symptoms when the participant was confident a headache would follow within 1-6 hours. Participants were randomized to treatment sequence A (placebo then ubrogepant 100 mg) or sequence B (ubrogepant 100 mg then placebo). This analysis evaluated the ability to function normally over 24 hours (secondary end point) and at specific time points after dose (additional end point). Other PRO end points included activity limitation over 24 hours and satisfaction with study medication at 8 and 24 hours. Of 518 randomized participants, 477 comprised the modified intent-to-treat population. After treatment of qualifying prodrome events, a significantly greater ability to function normally over 24 hours was observed for participants after treatment with ubrogepant 100 mg compared with placebo (odds ratio [OR] 1.66, 95% CI 1.40-1.96; p < 0.0001). As early as 2 hours after dose, a greater proportion of ubrogepant-treated participants reported "no disability, able to function normally" compared with placebo (OR 1.76, 95% CI 1.32-2.35; nominal p = 0.0001). Ubrogepant administered during the prodrome was also associated with a greater reduction in activity limitations over 24 hours after dose (OR 2.07, 95% CI 1.61-2.67; nominal p < 0.0001). At 8 and 24 hours after dose, rates of being "satisfied" or "extremely satisfied" were greater for ubrogepant than for placebo (8 hours: OR 2.37, 95% CI 1.78-3.15; nominal p < 0.0001; 24 hours: OR 2.32, 95% CI 1.78-3.02; nominal p < 0.0001). Ubrogepant 100 mg administered during the prodrome was associated with significantly greater ability to function normally, greater reduction in activity limitations over 24 hours, and greater satisfaction with study medication, compared with placebo. ClinicalTrials.gov NCT04492020. Submitted: July 27, 2020; first patient enrolled: August 21, 2020. clinicaltrials.gov/ct2/show/NCT04492020. This study provides Class II evidence that taking ubrogepant 100 mg during a migraine prodrome allows more patients to function normally over the next 24 hours.

Patients' Experiences During the Long Journey Before Initiating Migraine Prevention with a Calcitonin Gene-Related Peptide (CGRP) Monoclonal Antibody (mAb).

Migraine is under-diagnosed and under-treated. Many people with migraine do not seek medical care, and those who do may initially receive a different diagnosis and/or be dissatisfied with provided care on their journey before treatment with a CGRP-mAb (calcitonin-gene-related-peptide monoclonal antibody). This is a cross-sectional, self-reported, online survey of subjects in Lilly's Emgality® Patient Support Program in 2022. Questionnaires collected insights into subjects' prior experiences with migraine and interactions with healthcare professionals before receiving CGRP-mAbs. Of the 250 participants with episodic and 250 with chronic migraine, 90% were female and white with a mean age of 26.2years (±11.9) at diagnosis and 40.6 (±12.0) years at survey enrollment. Many participants (71%) suspected they had migraine before diagnosis, with 31% reluctant to seek help. Of these, approximately one-third were unaware of treatment, did not think that a physician could do anything more for migraine, would not take them seriously, or were reluctant due to a previous unhelpful experience. Participants mainly received information from friends/family (47%) or the internet (28%). Participants initially sought treatment due to an increase in migraine frequency (77%), attacks interfering with work or school (75%), or increased pain intensity (74%). Subjects saw a mean of 4.1 (±4.3) healthcare providers before migraine diagnosis, and 20% of participants previously received a different diagnosis. Participants reported migraine causes included stress/anxiety/depression (42%), hormonal changes (30%), nutrition (20%), and weather (16%). Acute treatment of migraine included prescription (82%) and over-the-counter (50%) medications, changes in nutrition (62%), adjusting fluid intake (56%), and relaxation techniques (55%). Preventive medications included anticonvulsants (61%), antidepressants (44%), blood pressure-lowering medications (43%), and botulinum toxin A injections (17%). Most discontinuations were due to lack of efficacy or side effects. People with migraine describe reluctance in seeking health care, and misunderstandings seem common especially in the beginning of their migraine journey. Graphical abstract available for this article.

Comparative effects of drug interventions for the acute management of migraine episodes in adults: systematic review and network meta-analysis

ObjectiveTo compare all licensed drug interventions as oral monotherapy for the acute treatment of migraine episodes in adults.DesignSystematic review and network meta-analysis.Data sourcesCochrane Central Register of Controlled Trials, Medline, Embase,...

Acute and preventive treatment of menstrual migraine: a meta-analysis

Background and objectivesAbout a quarter of migraine cases among women have menstrual migraine (MM), which is usually more severe, longer lasting, and less responsive to treatment than typical migraine. Randomized controlled trials (RCTs) have evaluated the efficacy of several medication in the acute and preventive treatment of MM; this meta-analysis compared the effectiveness of these treatments.MethodsWe conducted systematic searches in the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase databases. The primary outcomes of acute treatment trials were pain relief at 2 and 24 h after treatment compared with placebo or another treatment. The three endpoints we checked for studying MM prevention were: no recurrence of headaches each month, a 50% reduction in monthly migraine days from baseline, and a decrease in the mean number of headache days per month.ResultsOut of 342 studies, 26 RCTs met the criteria. Triptans, combined with or without other analgesics, were superior to placebo in providing pain relief in the acute treatment and prevention of MM. Among the treatments, sumatriptan and lasmiditan demonstrated superior pain relief at 2 h (OR: 4.62) and 24 h (OR: 4.81). Frovatriptan exhibited effectiveness in preventing headache recurrence, whereas galcanezumab and erenumab displayed significant preventive benefits in reducing headache days per month.ConclusionSumatriptan and lasmiditan are effective first-line treatments for acute MM. For prevention, frovatriptan may be the more effective of triptans. Compared with triptans, CGRP monoclonal antibodies, here including erenumab and galcanezumab, are more effective in reducing headache days, and therefore, in preventing MM.

Triptan non-response in a London tertiary headache centre: What can we learn? A retrospective study.

Triptans revolutionized the acute treatment of migraine; however, varied responses to triptans, as a result of poor efficacy and tolerability, are reported. A standardized definition of triptan non-response was recently proposed by the European Headache Federation (EHF). There is currently limited data available on the prevalence of triptan non-response. We used clinic letters over a two-year duration to evaluate the triptan response and triptan efficacy or tolerability failure, or both, in a London-based tertiary headache service. In total, 419 adult migraine patients (females: 83.8%, age: 46 ± 18years, chronic migraine: 88.5%) were included in a service evaluation. In line with the EHF definitions, "triptan non-response" was seen in 63.8% of patients (264/414), whereas 37.7% of patients (156/414) had failed at least two triptans (EHF "triptan resistant") and 4.6% of patients (19/414) had failed at least three triptans, including a subcutaneous formulation (EHF "triptan refractory"). Notably, 21.3% of patients (88/414) had failed at least three triptans inclusive and exclusive of subcutaneous triptan use. Advancing age (p < 0.001) and the presence of medication overuse (p = 0.006) increased the probability of triptan response, whereas an increased number of failed preventives (p < 0.001) and the use of calcitonin gene-related peptide monoclonal antibodies (p = 0.022) increased the probability of triptan non-response. The largest proportion of patients responded to eletriptan (49.5%), followed by nasal zolmitriptan (44.4%) and rizatriptan (35.7%). Our findings highlight an alarming prevalence of triptan non-response among adult migraineurs receiving treatment in a London-based tertiary headache service. It is imperative for clinicians to explore methods to optimize acute medication efficacy, whether this comprises changing to a triptan with a superior response rate, advocating for early intervention or considering alternative acute medication classes, such as gepants or ditans.

The Efficacy Of Continuous Non-Inhaled Intranasal Carbon Dioxide (CO2) In The Abortive Treatment Of Migraine: Results From Three Randomized, Double-Blinded, Placebo-Controlled Trials

Objective: Determining the efficacy, tolerability, and safety of continuous non-inhaled intranasal carbon dioxide (CO2) in the acute or abortive treatment of migraine. Background: Carbon dioxide gas infused in the nose and sinuses potentially blocks trigeminal nerve activation and subsequent neuropeptide release, probably through inhibition of voltage-gated channels. The pathogenesis of the migraine headache involves activation of the trigeminocervical system, which establishes the nociceptive innervation of the head through the trigeminal and occipital nerves. Methods: In three randomized, double-blinded, placebo-controlled trials, we randomized 350 subjects with migraine as defined by the International Headache Society (intent-to-treat population). We determined tolerability and safety in the 317 subjects who we exposed to treatment up to 24 hours post-dose (modified intent-to-treat population). We determined efficacy in the modified intent-to-treat and per-protocol populations at 15 minutes, half, one, two, and twenty-four hours post-dose in terms of pain freedom, freedom from headache-associated symptoms, and headache relief, treating migraine headaches of mild, moderate, or severe intensity. Results: We did not observe clinically significant systemic effects, either on blood carbon dioxide pressure or on the cardiovascular or respiratory system. No serious or clinically significant adverse events occurred and those reported were predominantly local, transient, and short-lived. Headache intensity strongly and in a negative way determined the efficacy of treatment with carbon dioxide but not with placebo, and even when placebo consisted of no gas, blinding seemed adequate. Conclusions: Continuous non-inhaled intranasal carbon dioxide seems safe, relatively well tolerated, and moderately effective for the acute or abortive treatment of migraine.