Acute Treatment Of Migraine Research Articles

Triptans in the Treatment of Acute Migraine in Children and Adolescents

Triptans in the Treatment of Acute Migraine in Children and Adolescents

Zavegepant Nasal Spray for Treatment of Acute Migraine: A Systematic Review

Background: Migraine is a widespread neurological disorder that can impair quality of life. Current treatments are often insufficient, with side effects causing some patients to seek alternative options. Zavegepant nasal spray, a new treatment being developed for acute migraine, shows promise in blocking the CGRP receptor and providing several potential advantages, such as faster onset of action and higher bioavailability. This systematic review aimed to assess the efficacy and safety of Zavegepant nasal spray in treating acute migraine attacks and identify adverse events.
 Methods: Adult patients diagnosed with acute migraine who were treated with Zavegepant nasal spray in randomized controlled trials (RCTs) or non-randomized clinical trials were included. A comprehensive search was conducted in PubMed, Embase, Cochrane Library, and ClinicalTrials.gov until March 2023. The following keywords were employed: "Zavegepant nasal spray", "migraine", "calcitonin gene-related peptide receptor antagonist." A narrative synthesis was conducted to summarize and analyze the extracted data from the included studies, with a focus on the efficacy and safety of Zavegepant nasal spray for the treatment of acute migraine.
 Results: This systematic review included three clinical trials, of which two were RCTs, and one was an open-label trial. The total number of participants was 3681, and all of them were in phase 2/3 of testing. The inclusion criteria for these trials were broadly based on individuals who had a history of migraines with or without aura lasting for over a year, which is consistent with the third edition of the International Classification of Headache Disorder. The findings were tabulated and discussed.
 Conclusion: Zavegepant nasal spray is an effective and well-tolerated treatment for acute migraines. Further research is needed to confirm its safety and efficacy, optimal dosing and administration, and effectiveness in different populations. The cost-effectiveness, patient satisfaction, and long-term effects on migraine burden ought to be investigated.

Celecoxib Oral Solution and the Benefits of Self-Microemulsifying Drug Delivery Systems (SMEDDS) Technology: A Narrative Review.

The oral route of drug delivery is the most widespread and preferred route of administration, but it has several limitations, including variable pharmacokinetics (PK), reduced dissolution and absorption, and gastrointestinal irritation. Further, many compounds have low aqueous solubility, which also limits intestinal absorption. For this narrative review, we conducted a literature search of PubMed until August 2022, focusing on emulsions, microemulsions, nanoemulsions, and self-emulsifying drug delivery systems. The self-microemulsifying drug delivery system (SMEDDS) overcomes these limitations of hydrophobic compounds to enhance their bioavailability. A SMEDDS formulation is a clear, thermodynamically stable, oil-in-water emulsion of lipid, solubilized drug, and two surfactants, which spontaneously forms droplets < 100nm in diameter. These components help deliver presolubilized drugs to the gastrointestinal tract, while protecting them from degradation in gastric acid or first-pass hepatic metabolism. SMEDDS formulations have improved oral drug delivery in the treatment of cancer (paclitaxel), viral infections (ritonavir), and migraine headache (ibuprofen and celecoxib oral solution). The American Headache Society recently updated their consensus statement for the acute treatment of migraine and included a selective cyclo-oxygenase-2 selective inhibitor formulated in SMEDDS, celecoxib oral solution. This SMEDDS formulation showed pronounced improvement in bioavailability compared with celecoxib capsules, allowing for a low dose of celecoxib in the oral solution to provide safe and effective acute migraine treatment. Here, we will focus on SMEDDS formulations, what differentiates them from other analogous emulsions as vehicles for poorly soluble drugs, and their clinical application in the acute treatment of migraine. Oral drugs reformulated in SMEDDS have shown accelerated times to peak plasma drug concentrations and increased maximum plasma concentrations, compared with capsules, tablets, or suspensions. SMEDDS technology increases both drug absorption and bioavailability of lipophilic drugs, compared with other formulations. Clinically, this allows the use of lower doses with improved PK profiles without compromising efficacy, as shown with celecoxib oral solution for the acute treatment of migraine.

Acute and prophylactic treatment of migraine

Migraine is a chronic neurological disorder that causes significant disability in patients and has a substantial economic impact in Canada. Effective treatment for migraine will improve our patients’ quality of life; additionally, it will reduce the economic burden generated by healthcare visits and employee absenteeism.&#x0D; The novel treatments in migraine target calcitonin gene-related peptide (CGRP), a neuropeptide which plays a role in the initiation of a migraine attack. Although our current understanding of migraine pathophysiology is incomplete, it is believed to involve the trigeminal nerve and its connections with the cerebral vasculature with nociceptive signals activated through a variety of neuropeptides including CGRP, substance P and nitric oxide.&#x0D; As a result of an improved understanding of migraine pathophysiology, the past several years have seen the advent of a variety of new therapeutic options in both the acute and prophylactic management of migraine. Although these agents represent additional options in the clinician’s arsenal, they have, in addition, introduced challenges in determining their cost-effectiveness. In this review, we provide an update on new acute and prophylactic migraine therapies and how they integrate into current practice from a primary care perspective.

Drugs for migraine.

Drugs for acute and preventive treatment of migraine, including analgesics, triptans, CGRP receptor antagonists. As well as nonpharmacologic acute and preventive treatment options (devices, other interventions).

Outcomes and Factors Associated with Insufficient Effectiveness of Acute Treatments of Migraine in Japan: Results of the ObserVational survey of the Epidemiology, tReatment, and Care Of MigrainE (OVERCOME [Japan]) Study.

Knowledge of patient outcomes and treatment effectiveness associated with acute migraine treatments in Japan is lacking. To describe patient-reported outcomes (PROs) and treatment effectiveness in three acute treatment groups from OVERCOME (Japan): over-the-counter (OTC) only, prescription nonsteroidal anti-inflammatory drugs/acetaminophen (Rx-NSAIDs/ACE) only, and triptans. OVERCOME (Japan) was an observational, cross-sectional, population-based web survey of people with migraine (July-September 2020). PROs, including the Migraine-Specific Quality of Life Questionnaire (MSQ), Migraine Interictal Burden Scale (MIBS-4), Migraine Disability Assessment (MIDAS), and Work Productivity and Activity Impairment Questionnaire: Migraine (WPAI-M), were compared pairwise between treatment groups. Logistic regression was used to examine treatment effectiveness. The analysis included 9075 survey respondents (OTC only: n=5791; Rx-NSAIDs/ACE only: n=751; triptans: n=2533). Triptan users reported the lowest MSQ scores, most severe disability (MIDAS: 20.7% versus 6.3% and 11.6%) and severe interictal burden (MIBS-4: 50.1% versus 21.2% and 19.8%), and greatest work impairment (WPAI-M: 50.4% versus 32.2% and 30.8%) compared with the OTC and Rx-NSAIDs/ACE groups, respectively. Treatment effectiveness was very poor-to-poor for 60.9%, 43.1%, and 47.6% of the triptan, OTC, and Rx-NSAIDs/ACE groups, respectively. Severe interictal burden was significantly associated with insufficient treatment effectiveness (odds ratios, severe versus no burden: 0.47 [95% confidence interval: 0.40-0.54], 0.56 [0.35-0.89], and 0.41 [0.32-0.52], for the OTC, Rx-NSAIDs/ACE, and triptan groups, respectively). People with high migraine burden used triptans for acute treatment, but many reported poor treatment effectiveness. Education may be required to promote better treatments, including earlier introduction of migraine-specific acute and preventive medications.

RWD65 Novel Adverse Events of CGRP Receptor Antagonists: A Disproportionality Analysis in USFDA Adverse Event Reporting System Database

Signal detection is a promising technique used for prompt detection of novel reactions. It is a modern method of detecting new reaction of a drug. Ubrogepant and Rimegepant are calcitonin gene-related peptide (CGRP) receptor antagonists were approved by US Food and Drug Administration (USFDA) in December 2019 and February 2020 respectively for acute treatment of Migraine. This study was to identify the signal strength for Ubrogepant and Rimegepant associated ADRs using data mining technique in USFDA adverse event reporting system (AERS) database.

Real-world study of intranasal ketamine for use in patients with refractory chronic migraine: a retrospective analysis

IntroductionSubanesthetic ketamine infusion has been used for managing refractory headache in inpatient or outpatient infusion settings. Intranasal ketamine may be an alternative option for outpatient care.MethodsA retrospective study was conducted...

Zavegepant: First Approval.

Zavegepant is a third generation, small-molecule, calcitonin gene-related peptide (CGRP) receptor antagonist being developed by Pfizer, under a license from Bristol-Myers Squibb, for the prevention and treatment of chronic and episodic migraine. In March 2023, zavegepant nasal spray (ZAVZPRET™) received its first approval in the USA for the acute treatment of migraine with or without aura in adults. Clinical development of an oral formulation of zavegepant is currently underway. This article summarizes the milestones in the development of zavegepant leading to this first approval for the acute treatment of migraine with or without aura in adults.

Safety and efficacy of rimegepant orally disintegrating tablet for the acute treatment of migraine in China and South Korea: a phase 3, double-blind, randomised, placebo-controlled trial

No acute treatments targeting calcitonin gene-related peptide (CGRP) have been approved for use in China or South Korea. We aimed to compare the efficacy and safety of rimegepant-an orally administered small molecule CGRP antagonist-with placebo in the acute treatment of migraine among adults in these countries. This double-blind, randomised, placebo-controlled, multicentre phase 3 trial was done at 86 outpatient clinics at hospitals and academic medical centres (73 in China and 13 in South Korea). Participants were adults (≥18 years) with at least a 1-year history of migraine who had two to eight moderate or severe attacks per month and fewer than 15 headache days per month within the 3 months before the screening visit. Participants were randomly assigned (1:1) to 75 mg rimegepant or placebo to treat a single migraine attack of moderate or severe pain intensity. Randomisation was stratified by the use of preventive medication and by country. The allocation sequence was generated and implemented by study personnel using an interactive web-response system accessed online from each study centre. All participants, investigators, and the sponsor were masked to treatment assignment. The coprimary endpoints of freedom from pain and freedom from the most bothersome symptom (nausea, phonophobia, or photophobia) 2 h after dosing were assessed in the modified intention-to-treat (mITT) population (randomly assigned participants who took study medication for a migraine attack of moderate or severe pain intensity, and provided at least one efficacy datapoint after treatment) using Cochran-Mantel Haenszel tests. Safety was assessed in all participants who received rimegepant or placebo. The study is registered with ClinicalTrials.gov, number NCT04574362, and is completed. 1431 participants were randomly assigned (716 [50%] to rimegepant and 715 [50%] to placebo). 668 (93%) participants in the rimegepant group and 674 (94%) participants in the placebo group received treatment. 1340 participants were included in the mITT analysis (666 [93%] in the rimegepant group and 674 [94%] in the placebo group). 2 h after dosing, rimegepant was superior to placebo for pain freedom (132 [20%] of 666 vs 72 [11%] of 674, risk difference 9·2, 95% CI 5·4-13·0; p<0·0001) and freedom from the most bothersome symptom (336 [50%] of 666 participants vs 241 [36%] of 674 participants, 14·8, 9·6-20·0; p<0·0001). The most common (≥1%) adverse events were protein in urine (8 [1%] of 668 participants in the rimepegant group vs 7 [1%] of 674 participants in the placebo group), nausea (7 [1%] of 668 vs 18 [3%] of 674), and urinary tract infection (5 [1%] of 668 vs 8 [1%] of 674). There were no rimegepant-related serious adverse events. Among adults living in China or South Korea, a single dose of 75 mg rimegepant was effective for the acute treatment of migraine. Safety and tolerability were similar to placebo. Our findings suggest that rimegepant might be a useful new addition to the range of medications for the acute treatment of migraine in China and South Korea, but further studies are needed to support long-term efficacy and safety and to compare rimegepant with other medications for the acute treatment of migraine in this population. BioShin Limited. For the Chinese and Korean translations of the abstract see Supplementary Materials section.

Rimegepant for migraine: acute efficacy beyond the USA

The safety and efficacy of rimegepant, a synthetic molecule that competes with calcitonin gene-related peptide (CGRP) for binding to its receptor, have been shown in two phase 3 studies on symptomatic treatment 1 Lipton RB Croop R Stock EG et al. Rimegepant, an oral calcitonin gene-related peptide receptor antagonist, for migraine. N Engl J Med. 2019; 381: 142-149 Crossref PubMed Scopus (177) Google Scholar , 2 Croop R Goadsby PJ Stock DA et al. Efficacy, safety, and tolerability of rimegepant orally disintegrating tablet for the acute treatment of migraine: a randomised, phase 3, double-blind, placebo-controlled trial. Lancet. 2019; 394: 737-745 Summary Full Text Full Text PDF PubMed Scopus (172) Google Scholar and one on prophylactic treatment 3 Croop R Lipton RB Kudrow D et al. Oral rimegepant for preventive treatment of migraine: a phase 2/3, randomised, double-blind, placebo-controlled trial. Lancet. 2021; 397: 51-60 Summary Full Text Full Text PDF PubMed Scopus (106) Google Scholar of migraine, all done in the USA. On the basis of these data, rimegepant was the first CGRP antagonist (gepant) to be approved by the US Food and Drug Administration and European Medicines Agency for both symptomatic and prophylactic treatment of migraine, giving it a unique and innovative role in the treatment of headaches. Rimegepant is available as a pill for oral administration as needed by people with migraine (ie, whenever they have a migraine attack 4 Mitsikostas DD Belesioti I Arvaniti C et al. Patients' preferences for headache acute and preventive treatment. J Headache Pain. 2017; 18: 102 Crossref PubMed Scopus (26) Google Scholar ), possibly without the risk of developing medication overuse headache, and without the need to take another medication for migraine prophylaxis. Until the development of the anti-CGRP treatments, all prophylactic anti-migraine medications had been repurposed from other diseases; these older treatments have little evidence of efficacy in migraine prophylaxis and have well known side-effects, which increases the likelihood that individuals have adverse events, reducing adherence and benefit. 5 Charles A Pozo-Rosich P Targeting calcitonin gene-related peptide: a new era in migraine therapy. Lancet. 2019; 394: 1765-1774 Summary Full Text Full Text PDF PubMed Scopus (157) Google Scholar By contrast, CGRP-pathway-targeting drugs are mechanism-based, are migraine-specific, and have very good evidence of tolerability and safety. 6 Hepp Z Dodick DW Varon SF Gillard P Hansen RN Devine EB Adherence to oral migraine-preventive medications among patients with chronic migraine. Cephalalgia. 2015; 35: 478-488 Crossref PubMed Scopus (254) Google Scholar Safety and efficacy of rimegepant orally disintegrating tablet for the acute treatment of migraine in China and South Korea: a phase 3, double-blind, randomised, placebo-controlled trialAmong adults living in China or South Korea, a single dose of 75 mg rimegepant was effective for the acute treatment of migraine. Safety and tolerability were similar to placebo. Our findings suggest that rimegepant might be a useful new addition to the range of medications for the acute treatment of migraine in China and South Korea, but further studies are needed to support long-term efficacy and safety and to compare rimegepant with other medications for the acute treatment of migraine in this population. Full-Text PDF

Device profile of Nerivio for the acute and preventive treatment of episodic or chronic migraine in patients 12 years and older

ABSTRACT Introduction Migraine is a prevalent, inherited and disabling brain disease with multiple symptoms and a variety of treatment options. Nerivio, utilizing remote electrical neuromodulation (REN) a wearable device, offers users good efficacy, tolerability and safety. It is user-friendly, affordable, non-addictive and cleared by the FDA and the European Conformity. Areas covered The device structure, mechanism of action, indications for use, application instructions, efficacy, adverse events, tolerability, safety, patient satisfaction, associated application and the research highlights are discussed herein. Expert opinion The device works well for most people living with migraine, often without concomitant medication, is tolerable, safe and causes minimal and mild adverse effects. It expands our migraine treatment options and improves patient adherence to treatment. Nerivio is easy-to-use and can be worn at any time of the day; it provides a non-pharmacologic option for the optimization of migraine treatment without significant adverse events.

Priority acute and preventive migraine treatment benefits: Results of the Migraine Clinical Outcome Assessment System (MiCOAS) qualitative study of people living with migraine.

There is renewed emphasis on including patients in determining, defining, and prioritizing outcomes for migraine treatment. To obtain insights directly from people living with migraine on their priorities for treatment. A total of 40 qualitative interviews were conducted as part of the Migraine Clinical Outcome Assessment System project, a United States Food and Drug Administration grant-funded program to develop a core set of patient-centered outcome measures for migraine clinical trials. Interviews included a structured exercise in which participants rank-ordered pre-defined lists of potential benefits for acute and preventive migraine therapy. The 40 study participants who reported being diagnosed with migraine by a clinician ranked the benefits and explained their rationale. Study participants consistently ranked either pain relief or absence of pain as their top priority for acute treatment. Relief/absence of other migraine symptoms and improved functioning were also prioritized. For preventive treatment, participants prioritized reductions in migraine frequency, symptom severity, and attack duration. Few differences were found between participants with episodic migraine and those with chronic migraine. However, participants with chronic migraine ranked "increased predictability of attacks" much higher than those with episodic migraine. Participants' rankings were influenced by prior expectations and experiences of migraine treatments, which caused many participants to deprioritize desired benefits as unrealistic. Participants also identified several additional priorities, including limited side-effects and reliable treatment efficacy in both acute and preventive treatments. The results showed the participants prioritized treatment benefits aligned with existing core clinical outcomes used in migraine research, but also valued benefits that are not typically assessed, such as predictability. Participants also deprioritized important benefits when they believed treatment was unlikely to deliver those outcomes.

INP104: a drug evaluation of a nonoral product for the acute treatment of migraine.

Migraine is a highly prevalent, disabling neurological disorder that is also associated with gastrointestinal symptoms, autonomic dysfunctionand allodynia. Despite the availability of multiple acute agents for migraine, an unmet need remains for effective, well-tolerated drugs that are nonoral and noninvasive. Here, we provide a drug evaluation of INP104, a novel drug-device combination product of dihydroergotamine (DHE) mesylate -a molecule with a long history of efficacy familiar to headache specialists -which is delivered to the difficult-to-reach upper nasal space where it is rapidly and consistently absorbed via Precision Olfactory Delivery (POD®). In clinical trials, INP104 exhibited favorable pharmacokinetics, a well-tolerated safety profile, and rapid symptom relief, highlighting its potential as a suitable acute therapy for migraine.

Patient Factors in the Dose Selection of Oral Sumatriptan for Acute Migraine: A Post Hoc Analysis of Two Randomized Controlled Studies.

Patients are seeking greater involvement in their healthcare. It therefore may be beneficial to provide guidance on initial oral sumatriptan dose selection for the treatment of acute migraine in nontraditional settings, such as telehealth and other remote forms of medical care. We sought to determine whether clinical or demographic factors are predictive of oral sumatriptan dose preference. This was a post hoc analysis of two clinical studies designed to determine preference for 25, 50, or 100mg oral sumatriptan. Patients were aged 18-65years with at least a 1year history of migraine and experienced, on average, between one and six severe or moderately severe migraine attacks per month, with or without aura. Predictive factors were demographic measures, medical history, and migraine characteristics. Possibly predictive factors were identified using three analyses: classification and regression tree analysis, marginal significance (P < 0.1) within a full-model logistic regression, and/or selection within a forward-selection procedure in a logistic regression. A reduced model containing the variables identified in the preliminary analyses was developed. Due to differences in study design, data were not combined. A dose preference was expressed by 167 patients in Study 1 and 222 patients in Study 2. Gender and medical history of urologic and/or psychological conditions in Study 1 and duration of migraine history, height, and medical history of endocrine or neurologic disease and headache severity in Study 2 were identified as possibly predictive. The predictive model showed low positive predictive value (PPV; 23.8%) and low sensitivity (21.7%) for Study 1. For Study 2, the model showed moderate PPV (60.0%) but low sensitivity (10.9%). No clinical or demographic characteristics alone or in combination were consistently or strongly associated with preference for oral sumatriptan dose level. The studies on which this paper is based were conducted before trial registration indexes were introduced.

Medication Preference, Satisfaction, and Clinical Improvement Among Adults Receiving Long-Term Treatment With Rimegepant for Migraine (P10-12.011)

Medication Preference, Satisfaction, and Clinical Improvement Among Adults Receiving Long-Term Treatment With Rimegepant for Migraine (P10-12.011)

Efficacy and Safety of Rimegepant for the Acute Treatment of Migraine in Black and African American Adults: Results From 3 Randomized, Placebo-Controlled Clinical Trials (P9-12.009)

Efficacy and Safety of Rimegepant for the Acute Treatment of Migraine in Black and African American Adults: Results From 3 Randomized, Placebo-Controlled Clinical Trials (P9-12.009)

Long-Term Preventive and Acute Treatment of Migraine With Rimegepant Improves Health Related Quality of Life (P12-12.003)

Long-Term Preventive and Acute Treatment of Migraine With Rimegepant Improves Health Related Quality of Life (P12-12.003)

Rimegepant for the Acute and Preventive Treatment of Migraine in Women: Results From 4 Randomized, Placebo-Controlled Clinical Trials (P9-12.007)

Rimegepant for the Acute and Preventive Treatment of Migraine in Women: Results From 4 Randomized, Placebo-Controlled Clinical Trials (P9-12.007)

Interim Analysis of STS101 Nasal Safety Data From the Phase 3 Open-Label ASCEND Migraine Study (P13-12.006)

<h3>Objective:</h3> To assess the long-term nasal safety and tolerability of STS101 in the acute treatment of migraine. <h3>Background:</h3> STS101 (dihydroergotamine nasal powder) is a novel investigational product with rapid and easy nasal delivery. The ASCEND study assesses the safety and tolerability of STS101 5.2 mg in the acute treatment of migraine with/without aura over 12 months. <h3>Design/Methods:</h3> ASCEND (NCT04406649) is a multi-center, multiple-dose, open-label study in adults (18–65 years) with migraine. Participants self-administered STS101 for ≤2 doses/24 hours and ≤12 doses/month for acute treatment of migraines for 12 months. This interim analysis included participants exclusively using the STS101 incorporating the second-generation nasal delivery device planned for commercialization. Nasal safety assessments included nasal treatment-emergent adverse events (TEAEs), subjective assessments of nasal irritation, and a smell test (SIT). Objective nasal assessments were done by trained study personnel on a 4-point severity scale to document nasal erythema, edema, rhinorrhea, bleeding, and nasal mucosa ulcerations. <h3>Results:</h3> This population included 344 subjects who treated 5,571 attacks with 6,918 doses of STS101 and was 40.4±10.9 years old (mean±SD), 85.8% female, and 87.5% Caucasian. Overall, 97 subjects (28.2%) reported nasal/local TEAEs; 8 of 344 subjects (2.9%) discontinued the study due to nasal/local TEAEs including nasal burning/discomfort (5), nasal bleeding (1), rhinitis (1), and throat tightness (1). Most frequently reported nasal/local related TEAEs were nasal discomfort (38 [11.0%] subjects; 338 [6.1%] attacks), dysgeusia (26 [7.6%]; 154 [2.8%]), and nasal congestion (14 [4.4%]; 198 [3.6%]). At 12 months, 99.5%, 95.4%, 93.5%, and 94.4% of subjects had no nasal bleeding/ulceration, edema, erythema, or rhinorrhea, respectively. No clinically relevant findings were seen from nasal examinations, subjective nasal irritation assessments, or smell tests. <h3>Conclusions:</h3> Nasal safety data from 5,571 treated attacks demonstrate the safety and tolerability of STS101 for the acute treatment of migraine. <b>Disclosure:</b> Dr. Spierings has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Manistee. Dr. Spierings has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Lundbeck. Dr. Spierings has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Lilly. Dr. Spierings has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Abbvie. Detlef Albrecht has received personal compensation for serving as an employee of Satsuma. Detlef Albrecht has stock in Satsuma. Dr. Rapoport has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for AbbVie, Amgen, Biohaven, Cala Health, Satsuma, Teva Pharmaceutical Industries, Theranica, Xoc and Zosano. Dr. Rapoport has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for AbbVie, Amgen, Biohaven, Lundbeck and Teva Pharmaceutical Industries. Dr. Rapoport has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurology Reviews.