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An episodic and chronic migraine affects approx 12% and 1% of the general population respectively.
The present study
concluded that the number of headache-free days’ increases with regular
functional performance in the patients with an episodic and chronic migraine
treated with fremanezumab.
An episodic and
chronic migraine affects approx 12% and 1% of the general population
respectively. A chronic migraine can be
defined as headaches occurring on at least 15 d/mo, with at least eight days of
a migraine per month. Migraine is ranked as seventh highest among medical
causes of disability worldwide. In a
recent study examining 2,959 patients with EM, 14.8% reported avoidance and
lifestyle compromise, 10.6% reported interictal anxiety, and 26% reported
interictal symptoms. Migraine should be best defined as a chronic neurologic
disorder with persistent interparoxysmal physiologic compromise rather than the
conventional view which illustrates migraine as an episodic or paroxysmal
headache disorder with attacks divided into discrete phases in between patients
which are symptom-free. It can be demonstrated as persistent symptoms
punctuated by continuous headache attacks and other attack-related symptoms
such as overlapping phases of prodrome (commonly referred to as premonitory),
aura, headache, and postdrome. Postdrome and prodrome symptoms are common and
affect around 80% of the migraine population. Phase related and interictal
non-headache symptom in addition to signs of frequent comorbid conditions is
essential in fully describing the burden of disease.
Fremanezumab,
formerly known as TEV-48125, is a humanised immunoglobulin G2a monoclonal
antibody that selectively binds to calcitonin gene-related peptide (CGRP) and
preventing its binding to receptors. Phase 2 and phase 3 trials assessing the
safety and efficacy have been completed for chronic and episodic migraines. In
the trials, a daily headache calendar was formed and completed. On headache
free days they were asked to answer questions focused on functional performance
for the day. The study was organised to evaluate the effect of fremanezumab on
functional performance on headache-free days.
Objective:
The purpose of this post hoc analysis was to determine the effect of
fremanezumab on the functional status on headache-free days in phase 2 an
episodic migraine (EM) and chronic migraine (CM) studies.
Study outcomes:
Time Points: 3 months
Outcomes
Baseline: There were no
significant differences observed at baseline
Study outcomes:
In both HFEM and
CM trials, patients with fremanezumab indicated an increase in the number of
headache-free days with regular functional performance in domains of work,
school, household chores, as well as energy and ability to concentrate when
compared to placebo. An increase in the headache-free days with the regular
performance was observed in HFEM trial with 225- and 675-mg doses of
fremanezumab and in CM trial with a 900-mg dose of fremanezumab. With an
increase in headache-free days, patients experienced a reduction in interictal
anxiety, avoidance behaviour and lifestyle compromise with normal functioning.
It is an important observation because all other preventive migraine therapies
lead to a variety of side effects (e.g., cognitive difficulties) contributing
to the burden of interictal symptom and reduction in medication adherence &
persistence.
Acute
medications for management of migraine are often administered at the onset of a
headache, but it can also be taken as the form of anticipatory treatment on
headache-free days in a subset of patients especially if prodromal symptoms are
experienced, in an attempt to preempt the headache phase. Additionally,
patients may also use acute treatment in the absence of a headache as an
anxiety response of fear of having a headache (cephalalgiaphobia). An increase
in headache-free days also reduces the intake of acute treatments resulting in
the decrease in any associated side effects that may contribute to impaired
functional performance on headache-free days. Overall, administration of
fremanezumab reduces the use of acute medications by 5 and 6.5 days/month
compared to the reduction of 3 and four days/month for those taking placebo
during the HFEM and CM studies.
Another
possibility is that there might be an effect on the prodrome, postdrome-, or
interictal-phase symptoms along with the headache phase of the attack on
headache-free days. The prodrome phase of migraine is thought to be centrally
mediated at the level of the hypothalamus. It is believed that fremanezumab
might have a direct effect on central networks because other CGRP-monoclonal
antibodies are not supposed to cross blood-brain barrier due to their high
molecular weight. Fremanzumab may also reduce the CGRP-mediated transmission in
the trigeminovascular system, and this reduction in peripheral afferent
activity can modulate the central networks that generated the migraine attack.
Modulation of CGRP also affects comorbid conditions such as depression,
anxiety, irritable bowel syndrome, and other chronic pain disorders that were
not assessed. Evaluation of the effect of CGRP-modulating therapies on
functional performance during headache-free days and on non-headache symptoms
helps to provide insight into potential pathophysiologic mechanisms of
migraine. It can also aid in illustrating the role of CGRP monoclonal
antibodies such as fremanezumab in the blockade on migraine-related
comorbidities and pathophysiology of migraine. Further prospective research is
warranted for the effect of CGRP monoclonal antibodies on headache-free days.
The present study introduces a novel and potentially
clinically meaningful endpoint that facilitates the measurement of more general
outcomes for patients about the mechanism of action of this class of biologics
and the mechanism of disease in migraine.
American Academy of Neurology
Fremanezumab for preventive treatment of migraine
Juliana VanderPluym et al.
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