Fremanezumab for the preventive treatment of chronic migraine

Stephen D. Silberstein, David William Dodick, Marcelo E. Bigal, Paul P. Yeung, Peter J. Goadsby, Tricia Blankenbiller, Melissa Grozinski-Wolff, Ronghua Yang, Yuju Ma, Ernesto Aycardi

Research output: Contribution to journalArticle

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Abstract

BACKGROUND Fremanezumab, a humanized monoclonal antibody targeting calcitonin gene-related peptide (CGRP), is being investigated as a preventive treatment for migraine. We compared two fremanezumab dose regimens with placebo for the prevention of chronic migraine. METHODS In this phase 3 trial, we randomly assigned patients with chronic migraine (defined as headache of any duration or severity on ≥15 days per month and migraine on≥8 days per month) in a 1:1:1 ratio to receive fremanezumab quarterly (a single dose of 675 mg at baseline and placebo at weeks 4 and 8), fremanezumab monthly (675 mg at baseline and 225 mg at weeks 4 and 8), or matching placebo. Both fremanezumab and placebo were administered by means of subcutaneous injection. The primary end point was the mean change from baseline in the average number of headache days (defined as days in which headache pain lasted ≥4 consecutive hours and had a peak severity of at least a moderate level or days in which acute migraine-specific medication [triptans or ergots] was used to treat a headache of any severity or duration) per month during the 12 weeks after the first dose. RESULTS Of 1130 patients enrolled, 376 were randomly assigned to fremanezumab quarterly, 379 to fremanezumab monthly, and 375 to placebo. The mean number of baseline headache days (as defined above) per month was 13.2, 12.8, and 13.3, respectively. The least-squares mean (□}SE) reduction in the average number of headache days per month was 4.3□}0.3 with fremanezumab quarterly, 4.6□}0.3 ith fremanezumab monthly, and 2.5□}0.3 with placebo (P<0.001 for both comparisons with placebo). The percentage of patients with a reduction of at least 50% in the average number of headache days per month was 38% in the fremanezumab- quarterly group, 41% in the fremanezumab- monthly group, and 18% in the placebo group (P<0.001 for both comparisons with placebo). Abnormalities of hepatic function occurred in 5 patients in each fremanezumab group (1%) and 3 patients in the placebo group (<1%). CONCLUSIONS Fremanezumab as a preventive treatment for chronic migraine resulted in a lower frequency of headache than placebo in this 12-week trial. Injection-site reactions to the drug were common. The long-term durability and safety of fremanezumab require further study.

Original languageEnglish (US)
Pages (from-to)2113-2122
Number of pages10
JournalNew England Journal of Medicine
Volume377
Issue number22
DOIs
StatePublished - Nov 30 2017

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Migraine Disorders
Placebos
Headache
Therapeutics
Tryptamines
Antibodies, Monoclonal, Humanized
Calcitonin Gene-Related Peptide
Subcutaneous Injections
Least-Squares Analysis
Safety
Pain
Injections
Liver

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Silberstein, S. D., Dodick, D. W., Bigal, M. E., Yeung, P. P., Goadsby, P. J., Blankenbiller, T., ... Aycardi, E. (2017). Fremanezumab for the preventive treatment of chronic migraine. New England Journal of Medicine, 377(22), 2113-2122. https://doi.org/10.1056/NEJMoa1709038

Fremanezumab for the preventive treatment of chronic migraine. / Silberstein, Stephen D.; Dodick, David William; Bigal, Marcelo E.; Yeung, Paul P.; Goadsby, Peter J.; Blankenbiller, Tricia; Grozinski-Wolff, Melissa; Yang, Ronghua; Ma, Yuju; Aycardi, Ernesto.

In: New England Journal of Medicine, Vol. 377, No. 22, 30.11.2017, p. 2113-2122.

Research output: Contribution to journalArticle

Silberstein, SD, Dodick, DW, Bigal, ME, Yeung, PP, Goadsby, PJ, Blankenbiller, T, Grozinski-Wolff, M, Yang, R, Ma, Y & Aycardi, E 2017, 'Fremanezumab for the preventive treatment of chronic migraine', New England Journal of Medicine, vol. 377, no. 22, pp. 2113-2122. https://doi.org/10.1056/NEJMoa1709038
Silberstein SD, Dodick DW, Bigal ME, Yeung PP, Goadsby PJ, Blankenbiller T et al. Fremanezumab for the preventive treatment of chronic migraine. New England Journal of Medicine. 2017 Nov 30;377(22):2113-2122. https://doi.org/10.1056/NEJMoa1709038
Silberstein, Stephen D. ; Dodick, David William ; Bigal, Marcelo E. ; Yeung, Paul P. ; Goadsby, Peter J. ; Blankenbiller, Tricia ; Grozinski-Wolff, Melissa ; Yang, Ronghua ; Ma, Yuju ; Aycardi, Ernesto. / Fremanezumab for the preventive treatment of chronic migraine. In: New England Journal of Medicine. 2017 ; Vol. 377, No. 22. pp. 2113-2122.
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abstract = "BACKGROUND Fremanezumab, a humanized monoclonal antibody targeting calcitonin gene-related peptide (CGRP), is being investigated as a preventive treatment for migraine. We compared two fremanezumab dose regimens with placebo for the prevention of chronic migraine. METHODS In this phase 3 trial, we randomly assigned patients with chronic migraine (defined as headache of any duration or severity on ≥15 days per month and migraine on≥8 days per month) in a 1:1:1 ratio to receive fremanezumab quarterly (a single dose of 675 mg at baseline and placebo at weeks 4 and 8), fremanezumab monthly (675 mg at baseline and 225 mg at weeks 4 and 8), or matching placebo. Both fremanezumab and placebo were administered by means of subcutaneous injection. The primary end point was the mean change from baseline in the average number of headache days (defined as days in which headache pain lasted ≥4 consecutive hours and had a peak severity of at least a moderate level or days in which acute migraine-specific medication [triptans or ergots] was used to treat a headache of any severity or duration) per month during the 12 weeks after the first dose. RESULTS Of 1130 patients enrolled, 376 were randomly assigned to fremanezumab quarterly, 379 to fremanezumab monthly, and 375 to placebo. The mean number of baseline headache days (as defined above) per month was 13.2, 12.8, and 13.3, respectively. The least-squares mean (□}SE) reduction in the average number of headache days per month was 4.3□}0.3 with fremanezumab quarterly, 4.6□}0.3 ith fremanezumab monthly, and 2.5□}0.3 with placebo (P<0.001 for both comparisons with placebo). The percentage of patients with a reduction of at least 50{\%} in the average number of headache days per month was 38{\%} in the fremanezumab- quarterly group, 41{\%} in the fremanezumab- monthly group, and 18{\%} in the placebo group (P<0.001 for both comparisons with placebo). Abnormalities of hepatic function occurred in 5 patients in each fremanezumab group (1{\%}) and 3 patients in the placebo group (<1{\%}). CONCLUSIONS Fremanezumab as a preventive treatment for chronic migraine resulted in a lower frequency of headache than placebo in this 12-week trial. Injection-site reactions to the drug were common. The long-term durability and safety of fremanezumab require further study.",
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AU - Dodick, David William

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AU - Goadsby, Peter J.

AU - Blankenbiller, Tricia

AU - Grozinski-Wolff, Melissa

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N2 - BACKGROUND Fremanezumab, a humanized monoclonal antibody targeting calcitonin gene-related peptide (CGRP), is being investigated as a preventive treatment for migraine. We compared two fremanezumab dose regimens with placebo for the prevention of chronic migraine. METHODS In this phase 3 trial, we randomly assigned patients with chronic migraine (defined as headache of any duration or severity on ≥15 days per month and migraine on≥8 days per month) in a 1:1:1 ratio to receive fremanezumab quarterly (a single dose of 675 mg at baseline and placebo at weeks 4 and 8), fremanezumab monthly (675 mg at baseline and 225 mg at weeks 4 and 8), or matching placebo. Both fremanezumab and placebo were administered by means of subcutaneous injection. The primary end point was the mean change from baseline in the average number of headache days (defined as days in which headache pain lasted ≥4 consecutive hours and had a peak severity of at least a moderate level or days in which acute migraine-specific medication [triptans or ergots] was used to treat a headache of any severity or duration) per month during the 12 weeks after the first dose. RESULTS Of 1130 patients enrolled, 376 were randomly assigned to fremanezumab quarterly, 379 to fremanezumab monthly, and 375 to placebo. The mean number of baseline headache days (as defined above) per month was 13.2, 12.8, and 13.3, respectively. The least-squares mean (□}SE) reduction in the average number of headache days per month was 4.3□}0.3 with fremanezumab quarterly, 4.6□}0.3 ith fremanezumab monthly, and 2.5□}0.3 with placebo (P<0.001 for both comparisons with placebo). The percentage of patients with a reduction of at least 50% in the average number of headache days per month was 38% in the fremanezumab- quarterly group, 41% in the fremanezumab- monthly group, and 18% in the placebo group (P<0.001 for both comparisons with placebo). Abnormalities of hepatic function occurred in 5 patients in each fremanezumab group (1%) and 3 patients in the placebo group (<1%). CONCLUSIONS Fremanezumab as a preventive treatment for chronic migraine resulted in a lower frequency of headache than placebo in this 12-week trial. Injection-site reactions to the drug were common. The long-term durability and safety of fremanezumab require further study.

AB - BACKGROUND Fremanezumab, a humanized monoclonal antibody targeting calcitonin gene-related peptide (CGRP), is being investigated as a preventive treatment for migraine. We compared two fremanezumab dose regimens with placebo for the prevention of chronic migraine. METHODS In this phase 3 trial, we randomly assigned patients with chronic migraine (defined as headache of any duration or severity on ≥15 days per month and migraine on≥8 days per month) in a 1:1:1 ratio to receive fremanezumab quarterly (a single dose of 675 mg at baseline and placebo at weeks 4 and 8), fremanezumab monthly (675 mg at baseline and 225 mg at weeks 4 and 8), or matching placebo. Both fremanezumab and placebo were administered by means of subcutaneous injection. The primary end point was the mean change from baseline in the average number of headache days (defined as days in which headache pain lasted ≥4 consecutive hours and had a peak severity of at least a moderate level or days in which acute migraine-specific medication [triptans or ergots] was used to treat a headache of any severity or duration) per month during the 12 weeks after the first dose. RESULTS Of 1130 patients enrolled, 376 were randomly assigned to fremanezumab quarterly, 379 to fremanezumab monthly, and 375 to placebo. The mean number of baseline headache days (as defined above) per month was 13.2, 12.8, and 13.3, respectively. The least-squares mean (□}SE) reduction in the average number of headache days per month was 4.3□}0.3 with fremanezumab quarterly, 4.6□}0.3 ith fremanezumab monthly, and 2.5□}0.3 with placebo (P<0.001 for both comparisons with placebo). The percentage of patients with a reduction of at least 50% in the average number of headache days per month was 38% in the fremanezumab- quarterly group, 41% in the fremanezumab- monthly group, and 18% in the placebo group (P<0.001 for both comparisons with placebo). Abnormalities of hepatic function occurred in 5 patients in each fremanezumab group (1%) and 3 patients in the placebo group (<1%). CONCLUSIONS Fremanezumab as a preventive treatment for chronic migraine resulted in a lower frequency of headache than placebo in this 12-week trial. Injection-site reactions to the drug were common. The long-term durability and safety of fremanezumab require further study.

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