To determine the number needed to treat (NNT) and number needed to harm (NNH) for atogepant for the preventive treatment of episodic migraine (EM).
Background:
Atogepant is an oral calcitonin gene–related peptide receptor antagonist approved for the preventive treatment of EM in adults. NNT and NNH are clinically relevant assessments of effect size that can inform management. The Migraine-Specific Quality of Life Questionnaire (MSQ v2.1) Role Function-Restrictive (RFR) domain assesses impacts of migraine on daily functioning that are important to people with migraine.
Design/Methods:
The ADVANCE trial (NCT02848326) was a 12-week, randomized, double-blind, placebo-controlled trial that evaluated the efficacy and safety of atogepant for the preventive treatment of EM. The NNT was calculated based on achievement of a ≥50% decrease in mean monthly migraine days (MMDs) (NNT≥50%) across 12 weeks. A second NNT was calculated based on achievement of a ≥10.9-point clinically relevant improvement from baseline in MSQ-RFR score (NNTMSQ-RFR) at week 12. NNH was calculated using the proportion of participants reporting a treatment-emergent adverse event (TEAE) leading to discontinuation.
Results:
A 50% reduction of MMDs from baseline was achieved by 56%–61% of atogepant participants versus 29% of placebo participants. The calculated NNTs≥50% for atogepant 10 mg, 30 mg, and 60 mg were 3.8, 3.4, and 3.1, respectively. The NNTsMSQ-RFR for the atogepant dose groups were 5.9, 5.7, and 6.3, respectively. TEAEs leading to discontinuation in participants treated with atogepant 10 mg, 30 mg, and 60 mg were reported by 4.1%, 1.8%, and 2.6% of participants, respectively, versus 2.7% of placebo-treated participants. The NNH was 73.0 for atogepant 10 mg. In the atogepant 30 mg and 60 mg dose groups, a lower percentage of participants discontinued versus placebo, resulting in negative NNT calculations (−105.5 and −949.7, respectively).
Conclusions:
These findings show a positive benefit-risk profile with atogepant for the preventive treatment of EM. Disclosure: Dr. Nahas has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for AbbVie. Dr. Nahas has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biohaven. Dr. Nahas has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Eli Lilly. Dr. Nahas has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Lundbeck. Dr. Nahas has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Teva. Dr. Nahas has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Theranica. Dr. Nahas has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for BioDelivery Sciences. Dr. Nahas has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Axsome. Dr. Nahas has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for AbbVie. Dr. Nahas has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Teva. Dr. Nahas has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Eli Lilly. Dr. Nahas has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Amgen. Dr. Nahas has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurology Learning Network. Dr. Nahas has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer. Dr. Nahas has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Jackson & Campbell. Dr. Nahas has received publishing royalties from a publication relating to health care. Dr. Nahas has received publishing royalties from a publication relating to health care. Dr. Nahas has received personal compensation in the range of $500-$4,999 for serving as a expert/talent for CME event with Medscape/WebMD. Dr. Ailani has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Allergan/Abbvie. Dr. Ailani has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Amgen. Dr. Ailani has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Eli Lilly. Dr. Ailani has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Lundbeck/Alder. Dr. Ailani has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Teva. Dr. Ailani has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Impel. Dr. Ailani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Satsuma. Dr. Ailani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Nesos. Dr. Ailani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GlaxoSmithKline. Dr. Ailani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BiodeliveryScienceIndustry. Dr. Ailani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Miravo. Dr. Ailani has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Pfizer. Dr. Ailani has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Impel. Dr. Ailani has received personal compensation in the range of $50,000-$99,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Allergan/Abbvie. Dr. Ailani has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biohaven. Dr. Ailani has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Theranica. Dr. Ailani has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Satsuma. Dr. Ailani has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Aeon. Dr. Ailani has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Axsome. Dr. Ailani has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eli Lilly. Dr. Ailani has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lindpharma. Dr. Ailani has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Current Pain and Headache Report. Dr. Ailani has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurology Live. Dr. Ailani has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Medscape. Dr. Ailani has stock in Ctrl M. The institution of Dr. Ailani has received research support from Allergan/Abbvie. The institution of Dr. Ailani has received research support from Eli Lilly. The institution of Dr. Ailani has received research support from Zosano. Dr. Ailani has received research support from Satsuma. Dr. Ailani has received personal compensation in the range of $500-$4,999 for serving as a Advisory Panel with Medscape. Dr. Ailani has received personal compensation in the range of $500-$4,999 for serving as a Medical Advisor with SELF. Dr. McAllister has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Aeon. Dr. McAllister has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for lilly. Dr. McAllister has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for teva. Dr. McAllister has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for abbvie. Dr. McAllister has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for biohaven. Dr. McAllister has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for lundbeck. Dr. McAllister has stock in Percept. Dr. Halker Singh has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Impel. Dr. Halker Singh has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Supernus. Dr. Halker Singh has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biohaven. Dr. Halker Singh has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Teva. Dr. Halker Singh has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Current Neurology & Neuroscience Reports. Dr. Halker Singh has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Headache Journal. Dr. Halker Singh has received publishing royalties from a publication relating to health care. Dr. Halker Singh has received publishing royalties from a publication relating to health care. Dr. Halker Singh has received personal compensation in the range of $5,000-$9,999 for serving as a CME speaker with Pri-med. Dr. Halker Singh has received personal compensation in the range of $5,000-$9,999 for serving as a CME speaker with Medscape. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Allergan/Abbvie. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Amgen. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biohaven. Dr. Lipton has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Eli Lilly. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Lundbeck. Dr. Lipton has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for GlaxoSmithKline. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Teva. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Vedanta. Dr. Lipton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Lipton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Satsuma. Dr. Lipton has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Eli Lilly. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Grifols. Dr. Lipton has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Allergan/Abbvie. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biohaven. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eli Lilly. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lundbeck. Dr. Lipton has stock in Biohaven. Dr. Lipton has stock in Manistee. The institution of Dr. Lipton has received research support from Teva. The institution of Dr. Lipton has received research support from Amgen. The institution of Dr. Lipton has received research support from Allergan/Abbvie. The institution of Dr. Lipton has received research support from Gammacore. The institution of Dr. Lipton has received research support from Axsome. The institution of Dr. Lipton has received research support from Charleston Labs. The institution of Dr. Lipton has received research support from Eli Lilly. The institution of Dr. Lipton has received research support from Satsuma. The institution of Dr. Lipton has received research support from NIH . The institution of Dr. Lipton has received research support from NIH. The institution of Dr. Lipton has received research support from NINDS. The institution of Dr. Lipton has received research support from NIH. The institution of Dr. Lipton has received research support from NIA. The institution of Dr. Lipton has received research support from NIH. The institution of Dr. Lipton has received research support from NIA. The institution of Dr. Lipton has received research support from NIH. The institution of Dr. Lipton has received research support from Veterans Administration. The institution of Dr. Lipton has received research support from NIH. Dr. Lipton has received publishing royalties from a publication relating to health care. Dr. Ma has received personal compensation for serving as an employee of AbbVie. Dr. Ma has received stock or an ownership interest from AbbVie. Pranav Gandhi has received personal compensation for serving as an employee of AbbVie. Pranav Gandhi has stock in AbbVie Inc. Dr. Smith has received personal compensation for serving as an employee of AbbVie. Dr. Smith has stock in AbbVie. Dr. Smith has received publishing royalties from a publication relating to health care. Dr. Liu has nothing to disclose. Dr. Chalermpalanupap has received personal compensation for serving as an employee of AbbVie. Dr. Chalermpalanupap has stock in AbbVie. Dr. Dabruzzo has received personal compensation for serving as an employee of AbbVie. Dr. Dabruzzo has stock in AbbVie.
Acute treatments for migraine and cluster headache are necessary to abort attacks, relieve pain and associated symptoms, and restore an individual's ability to function. Acute headache treatments consist of a variety of medication and nonmedication options. In this article, we discuss the approach to acute treatment of migraine and cluster headache. We summarize the level of evidence to support each acute medication class according to recent systematic reviews and meta-analyses, as well as guideline recommendations from the American Headache Society, American Academy of Neurology, and European Federation of Neurological Society.
Abstract This chapter discusses recurring headaches in medication-averse patients. When patients are averse to pharmaceutical intervention, it is worthwhile exploring their reasons, many of which are quite valid, including previous intolerable adverse effects. Overaggressive attempts to alter their preferences might be counterproductive, leading to a lack of trust and poor compliance. On the other hand, listening to their specific concerns and addressing them when possible might set the stage for introducing low-risk and well-tolerated medication, perhaps starting with very low dosages, in conjunction with nonpharmaceutical measures. These options include nutriceuticals, behavioral treatments, electrical and magnetic stimulation, and physical techniques such as massage.
Abstract This chapter discusses chronic headache in adolescents. Chronic migraine is disabling and has a significant impact on the adolescent’s self-esteem, quality of life (QOL), family and social functioning, and scholastic success. Yet, chronic migraine in this age group remains underdiagnosed, undertreated, and inadequately studied. The goals of migraine prevention are primarily to reduce the frequency and severity of individual attacks and to improve QOL. Typically, preventive treatments are initiated when attacks occur 4 or more days monthly or when migraine is disabling or negatively impacts QOL. In general, choosing migraine prevention is often based on the presence or absence of other comorbidities or co-occurring conditions. Migraine prevention encompasses lifestyle modifications as well as nonpharmacologic and pharmacological therapies. Lifestyle modifications include regular sleep patterns, eating habits, exercise routines, hydration, and stress reduction. Currently, only one preventive therapy (topiramate) is specifically approved for the prevention of migraine in adolescents, yet several are often used off-label.
Abstract Headache recurrence refers to the return of an episodic headache during the same migraine attack (within 24 hours) following the use of an acute treatment. This chapter on the acute treatment of migraine provides tips on questions to ask patients during the history to help clarify migraine attack frequency, headache frequency, and acute medication use to truly capture the complete clinical picture. The chapter provides a summary of traditional acute treatment options for migraine, specifically the triptans, and also summarizes the new acute options for migraine, including gepants and lasmiditan. In addition, the chapter provides commentary to help choose between these new options for a given patient who might not have found triptans helpful or has contraindications to using them.
Abstract This chapter investigates new daily persistent headache (NDPH), which is a rare primary headache disorder characterized by persistent headache with a particular profile because it starts one day with a clearly remembered onset and continues in a daily pattern. NDPH can have either chronic migraine or chronic tension-type headache features. Only a sudden onset and persistence are required for the diagnosis of NDPH. The most important first step in these cases is to exclude secondary causes; a number of occult mimics must be ruled out. However, treatment of NDPH is generally never fully effective. In clinical practice, most headache specialists treat NDPH based on the prominent headache phenotype, whether migrainous or tension-type. Medication overuse is frequently a problem, for obvious reasons, and must be dealt with in order to have a chance at successful outcome.
