Fremanezumab for preventive treatment of migraine

VanderPluym, Juliana; Dodick, David W.; Lipton, Richard B.; Ma, Yuju; Loupe, Pippa S.; Bigal, Marcelo E.

doi:10.1212/01.wnl.0000544321.19316.40

Cited by 42 publications

(40 citation statements)

References 37 publications

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“…The results presented here demonstrate that fremanezumab quarterly or monthly improved migraine-specific quality of life, overall health status, patients' global impression of change, and productivity in patients with CM. Taken in combination with the reduction in number of headache days demonstrated in the HALO CM trial 22 and an increase in number of headache-free days with normal functional performance observed in an analysis of a preceding phase 2 trial, 29 these results demonstrate that fremanezumab quarterly or monthly is an effective and well-tolerated treatment for patients with CM. Convergence of evidence from both patient-reported outcomes and more traditional efficacy measures of headache-free days supports the efficacy of fremanezumab in the treatment of CM.…”

Section: Discussionmentioning

confidence: 63%

Effect of fremanezumab on quality of life and productivity in patients with chronic migraine

et al. 2020

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Objective:To evaluate fremanezumab quarterly or monthly vs placebo on health-related quality of life, health status, patients’ global impression of change, and productivity in patients with chronic migraine (CM).Methods:HALO CM was a double-blind, placebo-controlled trial in patients with CM. Patients were randomized 1:1:1 to treatment with fremanezumab quarterly (675 mg at baseline, placebo at weeks 4 and 8), fremanezumab monthly (225 mg at baseline, weeks 4 and 8), or placebo. This manuscript assessed the effect of treatment with fremanezumab on health-related quality of life and productivity using the following prespecified assessments: the Migraine-Specific Quality of Life (MSQoL) questionnaire at baseline, weeks 4, 8, 12; Patient Global Impression of Change (PGIC) questionnaire at weeks 4, 8, 12; EuroQoL 5-dimension, 5-response level (EQ-5D-5L) questionnaire and Work Productivity and Activity Impairment: General Health (WPAI:GH) questionnaire at baseline and week 12.Results:The full analysis set included 1121 patients: 375 patients with quarterly dosing, 375 with monthly dosing, and 371 with placebo. Fremanezumab quarterly and monthly was associated with significant improvements over placebo in change from baseline mean scores in MSQoL domains (all, p < 0.05) to week 12. At week 12, fremanezumab also showed significant improvements in EQ-5D-5L visual analog scale (p < 0.05) and PGIC scores (p < 0.0001); as well as significant reductions from baseline in WPAI:GH scores (p < 0.01) and presenteeism (impairment while working; p < 0.05) vs placebo.Conclusions:Fremanezumab quarterly or monthly was associated with improvement over placebo in migraine-specific quality of life, overall health status, patients’ global impression of change with treatment, and productivity in patients with CM.

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Section: Discussionmentioning

confidence: 63%

Effect of fremanezumab on quality of life and productivity in patients with chronic migraine

et al. 2020

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“…The findings shown here may raise questions regarding the efficacy of CGRP/CGRP receptor monoclonal antibodies for migraine in males. Patient demographics from published clinical trials on erenumab, fremanezumab, galcanezumab, and eptinezumab all show patient populations that are Ͼ80% female, so it may not be clear whether these therapeutics are efficacious in a smaller percentage of males or whether higher doses may be required to achieve the same efficacy in males (Dodick et al, 2014b;Reuter et al, 2018;Rosen et al, 2018;VanderPluym et al, 2018). Alternatively, because we show that substantially lower doses of CGRP cause behavioral responses in females, the minimum concentration of CGRP necessary to contribute to migraine may be much lower in females, which may also be a contributing factor to why females are more susceptible to attacks.…”

Section: Discussionmentioning

confidence: 99%

Dural Calcitonin Gene-Related Peptide Produces Female-Specific Responses in Rodent Migraine Models

et al. 2019

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Migraine is the second leading cause for disability worldwide and the most common neurological disorder. It is also three times more common in women; reasons for this sex difference are not known. Using preclinical behavioral models of migraine, we show that application of calcitonin gene-related peptide (CGRP) to the rat dura mater produces cutaneous periorbital hypersensitivity. Surprisingly, this response was observed only in females; dural CGRP at doses from 1 pg to 3.8 g produce no responses in males. In females, dural CGRP causes priming to a pH 7.0 solution after animals recover from the initial CGRP-induced allodynia. Dural application of interleukin-6 causes acute responses in males and females but only causes priming to subthreshold dural CGRP (0.1 pg) in females. Intracisternal application of BDNF also causes similar acute hypersensitivity responses in males and females but only priming to subthreshold dural CGRP (0.1 pg) in females. Females were additionally primed to a subthreshold dose of the NO-donor sodium nitroprusside (0.1 mg/kg) following dural CGRP. Finally, the sexually dimorphic responses to dural CGRP were not specific to rats as similar female-specific hypersensitivity responses were seen in mice, where increased grimace responses were also observed. These data are the first to demonstrate that CGRP-induced headache-like behavioral responses at doses up to 3.8 g are female-specific both acutely and following central and peripheral priming. These data further implicate dural CGRP signaling in the pathophysiology of migraine and propose a model where dural CGRP-based mechanisms contribute to the sexual disparity of this female-biased disorder.Calcitonin gene-related peptide (CGRP) has long been implicated in the pathophysiology of migraine, and CGRP-based therapeutics are efficacious for the treatment of migraine in humans. However, the location of action for CGRP in migraine remains unclear. We show here that application of CGRP to the cranial meninges causes behavioral responses consistent with headache in preclinical rodent models. Surprisingly, however, these responses are only observed in females. Acute responses to meningeal CGRP are female-specific and sensitization to CGRP after two distinct stimuli are also female-specific. These data implicate the dura mater as a primary location of action for CGRP in migraine and suggest that female-specific mechanisms downstream of CGRP receptor activation contribute to the higher prevalence of migraine in women.

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“…VanderPluym et al [112] performed a post hoc analysis of the two phase 2b RCTs conducted by Teva Pharmaceuticals described above [81,82,112]. Participants were asked whether they had a headache of any severity on that day, and questions assessing impairment in their physical performance, concentration, and mental fatigue.…”

Section: Clinical Studies: Safety and Efficacymentioning

confidence: 99%

An Evidence-Based Review of Fremanezumab for the Treatment of Migraine

Urits

Clark

et al. 2020

Pain Ther

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Migraine headache is a common, chronic, debilitating disease with a complex etiology. Current therapy for migraine headache comprises either treatments targeting acute migraine pain or prophylactic therapy aimed at increasing the length of time between migraine episodes. Recent evidence suggests that calcium gene-related peptide (CGRP) is a critical component in the pathogenesis of migraines. Fremanezumab, a monoclonal antibody against CGRP, was recently approved by the Food and

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Fremanezumab for preventive treatment of migraine

Cited by 42 publications

References 37 publications

Effect of fremanezumab on quality of life and productivity in patients with chronic migraine

Effect of fremanezumab on quality of life and productivity in patients with chronic migraine

Dural Calcitonin Gene-Related Peptide Produces Female-Specific Responses in Rodent Migraine Models

An Evidence-Based Review of Fremanezumab for the Treatment of Migraine

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