Sustained reductions in migraine days, moderate-to-severe headache days and days with acute medication use for HFEM and CM patients taking fremanezumab: Post-hoc analyses from phase 2 trials

Rashmi B Halker Singh, Ernesto Aycardi, Marcelo E. Bigal, Pippa S. Loupe, Mirna McDonald, David William Dodick

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Background: In phase 2 and 3 studies, fremanezumab, a monoclonal CGRP antibody, was an effective preventive treatment for high-frequency episodic migraine (HFEM) and chronic migraine (CM). Objective: Post-hoc analyses evaluated population-wise 50%, 75% and 100% responder rates, and the extent to which individual responders sustained a 50%, 75% and 100% reduction in migraine days, moderate-to-severe (M/S) headache days and days of acute medication use during all three treatment months of the fremanezumab phase 2 studies. Design/methods: HFEM patients received either placebo or three once-monthly injections of 225 mg or 675 mg. CM patients received either placebo or three once-monthly injections of 900 mg, or an initial loading dose of 675 mg and subsequent injections of 225 mg. Patients reported headache-related data daily using an electronic diary. Results: In the HFEM study, the percent of patients on fremanezumab doses 225 mg and 675 mg were greater compared to the percent of placebo patients with sustained 50% reduction in migraine days (39% and 35% vs. 10% for placebo, both p < 0.0001), M/S headache days (36% and 38% vs. 16% placebo, p = 0.0017 and p = 0.0007 respectively), and acute medication use days (36% and 27% vs. 8% placebo, p < 0.0001 and p = 0.0003). Likewise, although there were fewer patients with sustained 75% reduction, there were increases in the percent of patients on fremanezumab 225 mg and 675 mg in the HFEM study relative to placebo patients in migraine days (19% and 11% vs. 3% placebo, p = 0.0002 and p = 0.0176), M/S headache days (19% and 15% vs. 2% placebo, p = 0.0001 and p = 0.0011) and days of acute medication use (16% and 8% vs. 2% placebo, p = 0.0005 and p = 0.0377). In the CM study, there were increases in the percent of patients on fremanezumab 675/225 mg and 900 mg with 50% sustained reduction in M/S headache days (32% and 40% vs. 15% placebo, p = 0.0058 and p = 0.0002) and days of acute medication use (26% and 22% vs. 11% placebo, p = 0.0098 and p = 0.0492). There were also increases in the percent of patients on fremanezumab 675/225 mg and 900 mg compared to patients on placebo with 75% sustained reduction in M/S headache days (10% and 13% vs. 3%, p = 0.0665 and p = 0.0203). Few patients had 100% sustained reductions in these parameters in either study. Conclusions: Post-hoc results must be interpreted with caution; nonetheless, a statistically significant percentage of patients who initially responded to fremanezumab within 1 month sustained this response over the subsequent 2 months. Sustained reduction in individual patients may provide a novel patient-centric, clinically meaningful endpoint for future trials assessing the effectiveness of preventive migraine treatments. Trials are registered as http://clinical trials.gov as NCT02025556 and NCT02021773.

Original languageEnglish (US)
Pages (from-to)52-60
Number of pages9
JournalCephalalgia
Volume39
Issue number1
DOIs
StatePublished - Jan 1 2019

Fingerprint

Migraine Disorders
Headache
Placebos
Injections
Therapeutics

Keywords

  • 100% responder rates
  • 50% responder rates
  • 75% responder rates
  • Fremanezumab
  • monoclonal CGRP antibody
  • preventive migraine treatment
  • TEV-48125

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Sustained reductions in migraine days, moderate-to-severe headache days and days with acute medication use for HFEM and CM patients taking fremanezumab : Post-hoc analyses from phase 2 trials. / Halker Singh, Rashmi B; Aycardi, Ernesto; Bigal, Marcelo E.; Loupe, Pippa S.; McDonald, Mirna; Dodick, David William.

In: Cephalalgia, Vol. 39, No. 1, 01.01.2019, p. 52-60.

Research output: Contribution to journalArticle

@article{9d0a222721aa4f6683d5147f785053e5,
title = "Sustained reductions in migraine days, moderate-to-severe headache days and days with acute medication use for HFEM and CM patients taking fremanezumab: Post-hoc analyses from phase 2 trials",
abstract = "Background: In phase 2 and 3 studies, fremanezumab, a monoclonal CGRP antibody, was an effective preventive treatment for high-frequency episodic migraine (HFEM) and chronic migraine (CM). Objective: Post-hoc analyses evaluated population-wise 50{\%}, 75{\%} and 100{\%} responder rates, and the extent to which individual responders sustained a 50{\%}, 75{\%} and 100{\%} reduction in migraine days, moderate-to-severe (M/S) headache days and days of acute medication use during all three treatment months of the fremanezumab phase 2 studies. Design/methods: HFEM patients received either placebo or three once-monthly injections of 225 mg or 675 mg. CM patients received either placebo or three once-monthly injections of 900 mg, or an initial loading dose of 675 mg and subsequent injections of 225 mg. Patients reported headache-related data daily using an electronic diary. Results: In the HFEM study, the percent of patients on fremanezumab doses 225 mg and 675 mg were greater compared to the percent of placebo patients with sustained 50{\%} reduction in migraine days (39{\%} and 35{\%} vs. 10{\%} for placebo, both p < 0.0001), M/S headache days (36{\%} and 38{\%} vs. 16{\%} placebo, p = 0.0017 and p = 0.0007 respectively), and acute medication use days (36{\%} and 27{\%} vs. 8{\%} placebo, p < 0.0001 and p = 0.0003). Likewise, although there were fewer patients with sustained 75{\%} reduction, there were increases in the percent of patients on fremanezumab 225 mg and 675 mg in the HFEM study relative to placebo patients in migraine days (19{\%} and 11{\%} vs. 3{\%} placebo, p = 0.0002 and p = 0.0176), M/S headache days (19{\%} and 15{\%} vs. 2{\%} placebo, p = 0.0001 and p = 0.0011) and days of acute medication use (16{\%} and 8{\%} vs. 2{\%} placebo, p = 0.0005 and p = 0.0377). In the CM study, there were increases in the percent of patients on fremanezumab 675/225 mg and 900 mg with 50{\%} sustained reduction in M/S headache days (32{\%} and 40{\%} vs. 15{\%} placebo, p = 0.0058 and p = 0.0002) and days of acute medication use (26{\%} and 22{\%} vs. 11{\%} placebo, p = 0.0098 and p = 0.0492). There were also increases in the percent of patients on fremanezumab 675/225 mg and 900 mg compared to patients on placebo with 75{\%} sustained reduction in M/S headache days (10{\%} and 13{\%} vs. 3{\%}, p = 0.0665 and p = 0.0203). Few patients had 100{\%} sustained reductions in these parameters in either study. Conclusions: Post-hoc results must be interpreted with caution; nonetheless, a statistically significant percentage of patients who initially responded to fremanezumab within 1 month sustained this response over the subsequent 2 months. Sustained reduction in individual patients may provide a novel patient-centric, clinically meaningful endpoint for future trials assessing the effectiveness of preventive migraine treatments. Trials are registered as http://clinical trials.gov as NCT02025556 and NCT02021773.",
keywords = "100{\%} responder rates, 50{\%} responder rates, 75{\%} responder rates, Fremanezumab, monoclonal CGRP antibody, preventive migraine treatment, TEV-48125",
author = "{Halker Singh}, {Rashmi B} and Ernesto Aycardi and Bigal, {Marcelo E.} and Loupe, {Pippa S.} and Mirna McDonald and Dodick, {David William}",
year = "2019",
month = "1",
day = "1",
doi = "10.1177/0333102418772585",
language = "English (US)",
volume = "39",
pages = "52--60",
journal = "Cephalalgia",
issn = "0333-1024",
publisher = "SAGE Publications Ltd",
number = "1",

}

TY - JOUR

T1 - Sustained reductions in migraine days, moderate-to-severe headache days and days with acute medication use for HFEM and CM patients taking fremanezumab

T2 - Post-hoc analyses from phase 2 trials

AU - Halker Singh, Rashmi B

AU - Aycardi, Ernesto

AU - Bigal, Marcelo E.

AU - Loupe, Pippa S.

AU - McDonald, Mirna

AU - Dodick, David William

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background: In phase 2 and 3 studies, fremanezumab, a monoclonal CGRP antibody, was an effective preventive treatment for high-frequency episodic migraine (HFEM) and chronic migraine (CM). Objective: Post-hoc analyses evaluated population-wise 50%, 75% and 100% responder rates, and the extent to which individual responders sustained a 50%, 75% and 100% reduction in migraine days, moderate-to-severe (M/S) headache days and days of acute medication use during all three treatment months of the fremanezumab phase 2 studies. Design/methods: HFEM patients received either placebo or three once-monthly injections of 225 mg or 675 mg. CM patients received either placebo or three once-monthly injections of 900 mg, or an initial loading dose of 675 mg and subsequent injections of 225 mg. Patients reported headache-related data daily using an electronic diary. Results: In the HFEM study, the percent of patients on fremanezumab doses 225 mg and 675 mg were greater compared to the percent of placebo patients with sustained 50% reduction in migraine days (39% and 35% vs. 10% for placebo, both p < 0.0001), M/S headache days (36% and 38% vs. 16% placebo, p = 0.0017 and p = 0.0007 respectively), and acute medication use days (36% and 27% vs. 8% placebo, p < 0.0001 and p = 0.0003). Likewise, although there were fewer patients with sustained 75% reduction, there were increases in the percent of patients on fremanezumab 225 mg and 675 mg in the HFEM study relative to placebo patients in migraine days (19% and 11% vs. 3% placebo, p = 0.0002 and p = 0.0176), M/S headache days (19% and 15% vs. 2% placebo, p = 0.0001 and p = 0.0011) and days of acute medication use (16% and 8% vs. 2% placebo, p = 0.0005 and p = 0.0377). In the CM study, there were increases in the percent of patients on fremanezumab 675/225 mg and 900 mg with 50% sustained reduction in M/S headache days (32% and 40% vs. 15% placebo, p = 0.0058 and p = 0.0002) and days of acute medication use (26% and 22% vs. 11% placebo, p = 0.0098 and p = 0.0492). There were also increases in the percent of patients on fremanezumab 675/225 mg and 900 mg compared to patients on placebo with 75% sustained reduction in M/S headache days (10% and 13% vs. 3%, p = 0.0665 and p = 0.0203). Few patients had 100% sustained reductions in these parameters in either study. Conclusions: Post-hoc results must be interpreted with caution; nonetheless, a statistically significant percentage of patients who initially responded to fremanezumab within 1 month sustained this response over the subsequent 2 months. Sustained reduction in individual patients may provide a novel patient-centric, clinically meaningful endpoint for future trials assessing the effectiveness of preventive migraine treatments. Trials are registered as http://clinical trials.gov as NCT02025556 and NCT02021773.

AB - Background: In phase 2 and 3 studies, fremanezumab, a monoclonal CGRP antibody, was an effective preventive treatment for high-frequency episodic migraine (HFEM) and chronic migraine (CM). Objective: Post-hoc analyses evaluated population-wise 50%, 75% and 100% responder rates, and the extent to which individual responders sustained a 50%, 75% and 100% reduction in migraine days, moderate-to-severe (M/S) headache days and days of acute medication use during all three treatment months of the fremanezumab phase 2 studies. Design/methods: HFEM patients received either placebo or three once-monthly injections of 225 mg or 675 mg. CM patients received either placebo or three once-monthly injections of 900 mg, or an initial loading dose of 675 mg and subsequent injections of 225 mg. Patients reported headache-related data daily using an electronic diary. Results: In the HFEM study, the percent of patients on fremanezumab doses 225 mg and 675 mg were greater compared to the percent of placebo patients with sustained 50% reduction in migraine days (39% and 35% vs. 10% for placebo, both p < 0.0001), M/S headache days (36% and 38% vs. 16% placebo, p = 0.0017 and p = 0.0007 respectively), and acute medication use days (36% and 27% vs. 8% placebo, p < 0.0001 and p = 0.0003). Likewise, although there were fewer patients with sustained 75% reduction, there were increases in the percent of patients on fremanezumab 225 mg and 675 mg in the HFEM study relative to placebo patients in migraine days (19% and 11% vs. 3% placebo, p = 0.0002 and p = 0.0176), M/S headache days (19% and 15% vs. 2% placebo, p = 0.0001 and p = 0.0011) and days of acute medication use (16% and 8% vs. 2% placebo, p = 0.0005 and p = 0.0377). In the CM study, there were increases in the percent of patients on fremanezumab 675/225 mg and 900 mg with 50% sustained reduction in M/S headache days (32% and 40% vs. 15% placebo, p = 0.0058 and p = 0.0002) and days of acute medication use (26% and 22% vs. 11% placebo, p = 0.0098 and p = 0.0492). There were also increases in the percent of patients on fremanezumab 675/225 mg and 900 mg compared to patients on placebo with 75% sustained reduction in M/S headache days (10% and 13% vs. 3%, p = 0.0665 and p = 0.0203). Few patients had 100% sustained reductions in these parameters in either study. Conclusions: Post-hoc results must be interpreted with caution; nonetheless, a statistically significant percentage of patients who initially responded to fremanezumab within 1 month sustained this response over the subsequent 2 months. Sustained reduction in individual patients may provide a novel patient-centric, clinically meaningful endpoint for future trials assessing the effectiveness of preventive migraine treatments. Trials are registered as http://clinical trials.gov as NCT02025556 and NCT02021773.

KW - 100% responder rates

KW - 50% responder rates

KW - 75% responder rates

KW - Fremanezumab

KW - monoclonal CGRP antibody

KW - preventive migraine treatment

KW - TEV-48125

UR - http://www.scopus.com/inward/record.url?scp=85056058488&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85056058488&partnerID=8YFLogxK

U2 - 10.1177/0333102418772585

DO - 10.1177/0333102418772585

M3 - Article

C2 - 29722276

AN - SCOPUS:85056058488

VL - 39

SP - 52

EP - 60

JO - Cephalalgia

JF - Cephalalgia

SN - 0333-1024

IS - 1

ER -