Andrew M. Blumenfeld . Benjamin M. Frishberg . Jack D. Schim .
Ashley Iannone . Gary Schneider . Larisa Yedigarova .
Aubrey Manack Adams
Received: December 18, 2020 / Accepted: April 1, 2021
The Author(s) 2021


Introduction: Combination use of onabo tulinumtoxinA and calcitonin gene–related peptide (CGRP) monoclonal antibodies (mAbs) has the potential to be more effective than either therapy alone for migraine prevention. 

Methods: This retrospective, longitudinal chart review included adults with chronic migraine treated at one clinical site with C 2 consecutive cycles of onabotulinumtoxinA and C 1 month of subsequent combination treatment with CGRP mAbs. Charts at time of mAb prescription (baseline) and up to four vis its * 3, 6, 9, and 12 months post-baseline were reviewed for safety, tolerability, and outcome measures (monthly headache days [MHDs], 


Why carry out this study?
A multimodal treatment approach that layers treatments targeting different physiological pathways involved in migraine may improve outcomes in patients with chronic migraine. OnabotulinumtoxinA and calcitonin gene–related peptide monoclonal antibodies (CGRP mAbs) act through different physiological mechanisms and are both effective and well tolerated when administered individually for the preventive treatment of migraine. We collected real-world data from chronic
migraine patients who received CGRP mAb treatment added to
onabotulinumtoxinA treatment to investigate the safety, tolerability, and potential benefits of this combination

What was learned from the study?
Adding a CGRP mAb to onabotulinumtoxinA was safe and well tolerated, with no new safety signals identified. Combination treatment significantly decreased monthly headache frequency and migraine-related disability compared with onabotulinumtoxinA alone.


This article is published with digital features, including a summary slide, to facilitate under standing of the article. To view digital features for this article go to https://doi.org/10.6084/ m9.figshare.14322125.
Individuals with chronic migraine (CM; C 15 monthly headache days [MHDs]) experience greater severity of migraine-associated disability  and greater prevalence of comorbid condi tions (e.g., other chronic pain disorders, anxi ety, depression) than those with less frequent migraine attacks (\ 15 MHDs). CM can greatly impair daily activities and quality of life, leading to substantial burden to the family and society. Given the high burden of CM, a multimodal management approach layering treatments that target different pathways involved in migraine pathophysiology may improve outcomes.
OnabotulinumtoxinA has been approved for CM prevention since 2010 and is well tolerated, with proven efficacy across multiple clinical and real-world studies. For CM, onabo tulinumtoxinA is injected into specific head and neck muscles containing sensory neuron endings with cell bodies located in trigeminal and cervical ganglia. By inhibiting activa tion of these sensory inputs, onabotulinum toxinA reduces the magnitude of pain signaling in the brain and prevents activation and sensi tization of central neurons thought to be involved in migraine chronification. A key mechanism of action of onabotulinumtoxinA is the attenuation of the release of neuropeptides and neurotransmitters into the synapse, and the insertion of receptors and ion channels into the nerve terminal membrane, which modulates the activation of receptors implicated in migraine pathophysiology, including gluta mate, substance P, and calcitonin gene–related peptide (CGRP). Attenuation of CGRP release from peripheral nerve terminals of meningeal and trigeminal nociceptors plays a key role in the effect of onabotulinumtoxinA on migraine.

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