Abstract and Introduction
Abstract
Objective: To incorporate recent research findings, expert consensus, and patient perspectives into updated guidance on the use of new acute and preventive treatments for migraine in adults.
Background: The American Headache Society previously published a Consensus Statement on the use of newly introduced treatments for adults with migraine. This update, which is based on the expanded evidence base and emerging expert consensus concerning postapproval usage, provides practical recommendations in the absence of a formal guideline.
Methods: This update involved four steps: (1) review of data about the efficacy, safety, and clinical use of migraine treatments introduced since the previous Statement was published; (2) incorporation of these data into a proposed update; (3) review and commentary by the Board of Directors of the American Headache Society and patients and advocates associated with the American Migraine Foundation; (4) consideration of these collective insights and integration into an updated Consensus Statement.
Results: Since the last Consensus Statement, no evidence has emerged to alter the established principles of either acute or preventive treatment. Newly introduced acute treatments include two small-molecule calcitonin gene-related peptide (CGRP) receptor antagonists (ubrogepant, rimegepant); a serotonin (5-HT1F) agonist (lasmiditan); a nonsteroidal anti-inflammatory drug (celecoxib oral solution); and a neuromodulatory device (remote electrical neuromodulation). New preventive treatments include an intravenous anti-CGRP ligand monoclonal antibody (eptinezumab). Several modalities, including neuromodulation (electrical trigeminal nerve stimulation, noninvasive vagus nerve stimulation, single-pulse transcranial magnetic stimulation) and biobehavioral therapy (cognitive behavioral therapy, biofeedback, relaxation therapies, mindfulness-based therapies, acceptance and commitment therapy) may be appropriate for either acute and/or preventive treatment; a neuromodulation device may be appropriate for acute migraine treatment only (remote electrical neuromodulation).
Conclusions: The integration of new treatments into clinical practice should be informed by the potential for benefit relative to established therapies, as well as by the characteristics and preferences of individual patients.
Introduction
Migraine is a chronic neurologic disease characterized by attacks of throbbing, often unilateral headache that are exacerbated by physical activity and associated with photophobia, phonophobia, nausea, vomiting,[1] and, frequently, cutaneous allodynia.[2–6] About one third of those with migraine have migraine with aura, and approximately three quarters experience a premonitory phase prior to the onset of headache.[7] Diagnoses of migraine can be refined based on the frequency of monthly migraine days (MMDs) and monthly headache days (MHDs) (Table 1).[1]
Migraine is widespread, and it can have a substantial burden of illness. The one-year period prevalence is 18% in women and 6% in men, and prevalence peaks between the ages of 25 and 55.[8–10] Migraine attacks can significantly impair functional ability at work or school, at home, and in social situations.[11–13] Among neurologic conditions, it ranks second worldwide in terms of years lost to disability.[14,15] Migraine is associated with a considerable financial burden, with annual total costs estimated at $27 billion in the United States,[16,17] and increased risk for a range of common health conditions, including anxiety, depression, asthma, epilepsy, and stroke.[18]
The pain and associated symptoms of migraine, as well as its life consequences, can be addressed with acute treatments, preventive treatments, or both.[19,20] However, because the severity, frequency, and characteristics of migraine vary among persons and, often, within individuals over time,[21] and symptom profiles or biomarkers that predict efficacy and side effects at the individual level have not yet been identified,[22,23] optimizing treatment for particular patients remains challenging. As a result, although the majority of patients with migraine respond to prescribed treatment(s), a process of trial and error is often necessary before a therapeutic plan can be individualized. To account for these challenges while ensuring access to cost-effective medical care, reimbursement decisions concerning migraine treatments must reflect these clinical realities.
The development and introduction of new medications and devices has led to important advances in the acute and preventive treatment of migraine. As a result, the appropriate and cost-effective integration of these new treatments remains a high priority for prescribing clinicians. The American Headache Society, consistent with its mission of improving the lives of individuals impacted by headache, previously established indications for which the initiation and continuation of novel acute and preventive treatments might be appropriate. For this update, the Society convened a task force (the authors JA, RCB, and MSR) to review the literature published since December 2018 and to revise the document based on its findings. The initial literature review was performed by JA, RCB, and MSR in September 2019. Additional relevant information, including subsequently published clinical trials and regulatory updates, was included through February 2021. Commentary on the revision was provided by the Board of Directors of the American Headache Society and patients and patient advocates associated with the American Migraine Foundation. The AHS Board of Directors provided final review of the Consensus Statement in February 2021.
The resulting update to The American Headache Society Position Statement On Integrating New Migraine Treatments Into Clinical Practice is designed to offer prescribing clinicians with guidance in the use of established and recently approved therapies for the acute and preventive treatment of migraine, including the goals of treatment, approved indications for usage, and strategies for developing personalized treatment plans. Like its predecessor, this Statement uses the recommendations of the US Headache Consortium as a starting point,[22,24–28] but it incorporates information that has become available since the first Statement was published, including new recommendations about the use of novel treatments approved for the acute and preventive treatment of migraine and an evidence-based update on the long-term safety of monoclonal antibodies (mAbs) to calcitonin gene-related peptide (CGRP) and its receptor for the preventive treatment of migraine.
As in the first Consensus Statement, the objective of this document is to improve outcomes among patients with migraine who have unmet needs by helping clinicians identify and develop successful, evidence-based treatment plans for those most likely to benefit from a trial of a new therapy. Although it provides timely recommendations to clinicians and their patients with migraine, this Consensus Statement is not intended to be, and should not be understood or applied as, a Clinical Practice Guideline. Expert consensus about optimal sequencing and layering of acute and preventive treatments (e.g., migraine-specific vs. nonspecific), as well as definitive guidance distinguishing the efficacy, tolerability, and safety of new treatments relative to established treatments and each other, await the results of studies designed to answer these important questions. In the meantime, the Society recommends that within migraine-specific acute therapies and preventive treatments, generalized step-care strategies be adjusted to meet the medical needs of individual patients. Individualized treatment plans are more likely to provide appropriate therapy at the initial consultation and spare patients a series of failed therapeutic efforts,[29,30] yielding both better clinical outcomes and lower healthcare costs.
Readers are advised that this Statement has been reorganized. The section on acute treatment now precedes preventive treatment, which more closely aligns with the experience of migraine in clinical practice. The previous subcategory of Patient Identification now appears under the single subcategory of Indications. A new section addresses treatments that provide therapeutic benefits as acute and preventive therapies.