No evidence suggests migraine prevention treatment, including monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) pathway or onabotulinumtoxinA (Botox) injections, should be delayed if migraine patients are scheduled to receive a COVID-19 vaccine, experts said.
The established risks of COVID-19 infection and the efficacy of migraine preventive therapies "underscore the importance of not delaying either of these interventions," wrote Amy Gelfand, MD, of the University of California San Francisco, and Gregory Poland, MD, director of the Mayo Clinic Vaccine Research Group in Rochester, Minnesota, in an editorial published in .
"We have no data that suggests interference with the COVID-19 response by any of the drugs used in treatment for migraine and other headache disorders," said Poland, the editor-in-chief of Vaccine, in an interview with 51˶.
"It's not necessary to re-time your migraine preventive treatments with regards to timing of your COVID-19 vaccine doses," added Gelfand, the editor of Headache. "If you experience headache or fever after the vaccine and want to take something to treat those symptoms, taking NSAIDs or acetaminophen will not harm your ability to make an immune response to the vaccine," she told 51˶.
In January, Gelfand asked the Twitter headache community: "Headache providers: What questions are your patients asking you about the COVID vaccine? What information do you wish you had to be able to counsel them better?"
The Headache editorial was a response to queries that emerged from that tweet. Clinical questions fell into two broad categories: whether migraine treatment affected the efficacy or safety of COVID-19 vaccines, and whether the vaccine impaired the effectiveness of migraine treatment.
"These questions seem to have focused most on onabotulinumtoxinA and the CGRP pathway monoclonal antibodies, perhaps because they are delivered by injection," Gelfand and Poland observed.
A frequent question was whether to defer monthly or quarterly CGRP pathway monoclonal antibody treatment by 2 weeks from the vaccine. Monoclonal antibodies targeting the CGRP pathway include erenumab (Aimovig), fremanezumab (Ajovy), galcanezumab (Emgality), and eptinezumab (Vyepti).
Currently, only mRNA, adenovirus-vectored, and purified protein COVID-19 vaccines are or are likely to soon be available, Gelfand and Poland noted. "In each of these vaccine platforms, the only SARS-CoV-2 virally-derived immunologic target present is the SARS-CoV-2 full-length S (spike) protein encoded either in mRNA (Pfizer and Moderna vaccines), DNA (adenovirus-vectored vaccines; AstraZeneca or Johnson & Johnson), or the purified S protein with a proprietary adjuvant (Novavax)," they wrote.
Vaccine-induced protective immune responses are confined to the spike protein and its epitopes, and there's no reason to think antibodies to the SARS-CoV-2 spike protein would neutralize onabotulinumtoxinA or antibodies to CGRP or its receptor, Poland pointed out.
"Remember that with monoclonal antibodies, you are giving precision therapy. You're giving a key that fits into a lock and other keys don't fit that lock," he said. "As far as I can even imagine, none of the CGRP monoclonal antibodies are going to impact the immune response to a COVID vaccine because they're different biologies and different mechanisms of action and they don't overlap. The same with onabotulinumtoxinA."
Headache patients who use NSAIDs or acetaminophen should continue if needed, Poland added. "There's been a concern over a mild decrease in antibody level, seen primarily with first doses of standard infant vaccines and not so much with adult vaccines in general," he said. "No one has studied this precisely with COVID vaccines. However, in the AstraZeneca trial, several of the clinical trial sites pre-dosed with acetaminophen."
"Like everything in life, you're balancing risk and benefit," Poland continued. "If an important part of your headache treatment of prevention regimen is the use of acetaminophen or a non-steroidal drug, I would not stop that in the face of a COVID vaccine."
While many patients with migraine and other headache disorders likely entered the COVID-19 vaccine clinical trials, specific data about them have not been reported. Because there's no published data about headache patients and the vaccine, the Headache editorial is based on expert opinion, Gelfand and Poland noted.
"As always, individual patients should make treatment decisions in concert with their treating healthcare professionals, taking into account their individual circumstances," they wrote.
Disclosures
Gelfand has received honoraria from UpToDate (for authorship) and JAMA Neurology. She receives payment from the American Headache Society for her role as editor of Headache. She receives grant support from Amgen and the Duke Clinical Research Institute.
Poland reported relationships with Merck, Medicago, GlaxoSmithKline, Sanofi Pasteur, Emergent BioSolutions, Dynavax, Genentech, Eli Lilly and Company, Janssen Global Services LLC, Kentucky BioProcessing, AstraZeneca, and Genevant Sciences, Inc. He holds patents related to vaccinia and measles peptide vaccines, and has received grant funding from ICW Ventures for preclinical studies on a peptide-based COVID-19 vaccine.
Primary Source
Headache
Gelfand AA, Poland G "Migraine treatment and COVID-19 vaccines: no cause for concern" Headache 2021; DOI: 10.1111/head.14086.