Efficacy, safety, and tolerability of rimegepant orally disintegrating tablet for the acute treatment of migraine: a randomised, phase 3, double-blind, placebo-controlled trial

Croop, Robert; Goadsby, PJ; Stock, David A.; Conway, Charles M.; Forshaw, Micaela; Stock, E.; Coric, Vladimir; Lipton, Richard B.

doi:10.1016/s0140-6736(19)31606-x

Cited by 264 publications

(330 citation statements)

References 24 publications

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“…[5][6][7][8][9][10][11][12][13][14][15][16][17] It should be noted that clinical trials have taken 2 approaches to determining MBS; some determine MBS during a clinic visit, 6,14,15 while others determine MBS immediately prior to taking study medication. 7,9,10,12,13,16 The MAST survey used a recallbased question about MBS with headache attacks over the last 3 months. When study respondents report their MBS prior to treatment, several factors may influence their response.…”

Section: Discussionmentioning

confidence: 99%

“…Missed and reduced productivity days items were summed and grouped to identify disability by 4 grades: little or none (score of 0-5), mild (score of 6-10), moderate (score of [11][12][13][14][15][16][17][18][19][20], and severe (score of ≥21). Migraine-related disability was assessed with the Migraine Disability Assessment (MIDAS) questionnaire, a 5-item scale assessing missed and reduced productivity days at work, school, or home during the previous 3 months due to headache.…”

Section: Studymentioning

confidence: 99%

“…Migraine-related disability was assessed with the Migraine Disability Assessment (MIDAS) questionnaire, a 5-item scale assessing missed and reduced productivity days at work, school, or home during the previous 3 months due to headache. Missed and reduced productivity days items were summed and grouped to identify disability by 4 grades: little or none (score of 0-5), mild (score of 6-10), moderate (score of [11][12][13][14][15][16][17][18][19][20], and severe (score of ≥21).…”

Section: Studymentioning

confidence: 99%

“…By removing the need to show significant differences from placebo on 4 coprimary endpoints, the new approach also reduces sample size requirements and increases power to detect change relative to trials conducted under the older guidance. 3,4 Though multiple acute treatment studies have been conducted using 2-hour MBS freedom as a coprimary endpoint, [5][6][7][8][9][10][11][12][13][14][15][16][17] we are not aware of data on MBS in nationally representative samples of people with migraine. The Migraine in America Symptoms and Treatment (MAST) Study was designed to assess current patterns of consultation, diagnosis, and treatment in a large representative sample of people with migraine in the United States.…”

Section: Introductionmentioning

confidence: 99%

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Most Bothersome Symptom in Persons With Migraine: Results From the Migraine in America Symptoms and Treatment (MAST) Study

Munjal¹,

Singh²,

Reed³

et al. 2019

Headache

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Objectives.-The objectives of this study were to determine the rates of nausea, phonophobia, and photophobia reported overall and as the most bothersome symptom (MBS) in individuals with migraine and to identify individual characteristics associated with each of the 3 candidate MBSs.Background.-The MBS has emerged as an important coprimary efficacy endpoint in clinical trials of acute treatments for migraine, as recommended by the Food and Drug Administration. The current understanding of how persons with migraine designate an associated symptom as the most bothersome has been assessed primarily in the context of randomized trials. Methods.-Respondents (n = 95,821) in the cross-sectional, observational Migraine in America Symptoms and Treatment (MAST) study were adults (aged ≥18 years) recruited from a US nationwide online research panel. A validated diagnostic screener identified 15,133 individuals who met modified International Classification of Headache Disorders (ICHD)-3 betacriteria for migraine and reported at least 1 monthly headache day (MHD) over the previous 3 months. The survey ascertained sociodemographic variables, headache-related disability, MHDs, cutaneous allodynia, medication overuse, a migraine symptom severity score, pain interference, noncephalic pain, anxiety and depression symptoms, visual aura over the previous year, and acute treatment optimization. The current analysis is based on respondents who also completed a 6-month follow-up assessment that included questions about their most bothersome headache symptom.Results.-A total of 7518 respondents completed the 6-month follow-up, and 6045 met inclusion criteria and were included in the analysis. The mean age of respondents was 47 (SD 13.4) years, 76.0% (4596/6045) were women, and 84.8% (5103/6017) were white. Among all respondents, 64.9% reported all 3 migraine symptoms. The MBS was photophobia in 49.1% (2967/6045), nausea in 28.1% (1697/6045), and phonophobia in 22.8% (1381/6045). Respondents reporting photophobia as the MBS were more likely to be men, to be obese, and to report visual aura. Those reporting nausea as the MBS were more likely to be women, to have lower incomes, and to report lower levels of treatment optimization. Respondents reporting phonophobia as the MBS were more likely to have cutaneous allodynia and less likely to have visual aura.Conclusion.-Most people with migraine in the MAST observational study reported all 3 cardinal symptoms of nausea, photophobia, and phonophobia. As in clinical trials, the most common MBS was photophobia. Patient profiles differed among the groups defined by their MBS.

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Section: Discussionmentioning

confidence: 99%

Section: Studymentioning

confidence: 99%

Section: Studymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Most Bothersome Symptom in Persons With Migraine: Results From the Migraine in America Symptoms and Treatment (MAST) Study

Munjal¹,

Singh²,

Reed³

et al. 2019

Headache

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“…Recent studies have inconsistent results regarding the efficacy and tolerability of rimegepant. (Loder and Tfelt-Hansen, 2019); Our meta-analysis included four RCTs c (Marcus et al, 2014;60th Annual Scientific Meeting American Headache Society, 2018;Lipton et al, 2019;Croop et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Efficacy and Safety of Rimegepant for the Acute Treatment of Migraine: Evidence From Randomized Controlled Trials

et al. 2020

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Background: As one of the novel therapeutic drugs that targets Calcitonin gene-related peptide (CGRP), 75 mg rimegepant has been used for the acute management of migraine, which is one of the most common neurological diseases worldwide. Several clinical trials have been conducted to investigate the efficacy and safety of rimegepant for the acute management of migraine, but no systematic review of existing literature has been performed. We therefore performed a meta-analysis to investigate the efficacy and safety of rimegepant in treatment of patients with migraine. Method: Pubmed, Embased, and Cochrane Library were searched from January 2001 to August 2019 for randomized controlled trials (RCTs). Four RCTs with 3,827 patients were finally included in our study. Result: We pooled 3,827 patients from four RCTs, and the primary endpoints were freedom from pain, most bothersome symptom, and pain relief at 2 hr post dose. We found that 75 mg rimegepant led to significant freedom from pain (P < 0.001), pain relief (P < 0.001), and freedom from the most bothersome symptom (P < 0.001) at 2 hr post dose compared with the placebo. In addition, there was no statistically significant increase in adverse events compared with the placebo. Conclusions: 75 mg rimegepant had good efficacy and safety for acute treatment of migraine. Further studies are needed to compare the efficacy of rimegepant with traditional drugs for acute management of migraine.

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Effect of Ubrogepant vs Placebo on Pain and the Most Bothersome Associated Symptom in the Acute Treatment of Migraine

Lipton

Dodick

Ailani

et al. 2019

JAMA

203

302

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IMPORTANCE Ubrogepant is an oral calcitonin gene-related peptide receptor antagonist under investigation for acute treatment of migraine. OBJECTIVE To evaluate the efficacy and tolerability of ubrogepant compared with placebo for acute treatment of a single migraine attack. DESIGN, SETTING, AND PARTICIPANTS Phase 3, multicenter, randomized, double-blind, placebo-controlled, single-attack, clinical trial (ACHIEVE II) conducted in the United States (99 primary care and research clinics; August 26, 2016-February 26, 2018). Participants were adults with migraine with or without aura experiencing 2 to 8 migraine attacks per month. INTERVENTIONS Ubrogepant 50 mg (n = 562), ubrogepant 25 mg (n = 561), or placebo (n = 563) for a migraine attack of moderate or severe pain intensity. MAIN OUTCOMES AND MEASURES Co-primary efficacy outcomes were pain freedom and absence of the participant-designated most bothersome migraine-associated symptom (among photophobia, phonophobia, and nausea) at 2 hours after taking the medication. RESULTS Among 1686 randomized participants, 1465 received study treatment (safety population; mean age, 41.5 years; 90% female); 1355 of 1465 (92.5%) were evaluable for efficacy. Pain freedom at 2 hours was reported by 101 of 464 participants (21.8%) in the ubrogepant 50-mg group, 90 of 435 (20.7%) in the ubrogepant 25-mg group, and 65 of 456 (14.3%) in the placebo group (absolute difference for 50 mg vs placebo, 7.5%; 95% CI, 2.6%-12.5%; P = .01; 25 mg vs placebo, 6.4%; 95% CI, 1.5%-11.5%; P = .03). Absence of the most bothersome associated symptom at 2 hours was reported by 180 of 463 participants (38.9%) in the ubrogepant 50-mg group, 148 of 434 (34.1%) in the ubrogepant 25-mg group, and 125 of 456 (27.4%) in the placebo group (absolute difference for 50 mg vs placebo, 11.5%; 95% CI, 5.4%-17.5%; P = .01; 25 mg vs placebo, 6.7%; 95% CI, 0.6%-12.7%; P = .07). The most common adverse events within 48 hours of any dose were nausea (50 mg, 10 of 488 [2.0%]; 25 mg, 12 of 478 [2.5%]; and placebo, 10 of 499 [2.0%]) and dizziness (50 mg, 7 of 488 [1.4%]; 25 mg, 10 of 478 [2.1%]; placebo, 8 of 499 [1.6%]). CONCLUSIONS AND RELEVANCE Among adults with migraine, acute treatment with ubrogepant compared with placebo led to significantly greater rates of pain freedom at 2 hours with 50-mg and 25-mg doses, and absence of the most bothersome migraine-associated symptom at 2 hours only with the 50-mg dose. Further research is needed to assess the effectiveness of ubrogepant against other acute treatments for migraine and to evaluate the long-term safety of ubrogepant among unselected patient populations.

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Efficacy, safety, and tolerability of rimegepant orally disintegrating tablet for the acute treatment of migraine: a randomised, phase 3, double-blind, placebo-controlled trial

Cited by 264 publications

References 24 publications

Most Bothersome Symptom in Persons With Migraine: Results From the Migraine in America Symptoms and Treatment (MAST) Study

Most Bothersome Symptom in Persons With Migraine: Results From the Migraine in America Symptoms and Treatment (MAST) Study

Efficacy and Safety of Rimegepant for the Acute Treatment of Migraine: Evidence From Randomized Controlled Trials

Effect of Ubrogepant vs Placebo on Pain and the Most Bothersome Associated Symptom in the Acute Treatment of Migraine

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