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      Real-world persistence and costs among patients with chronic migraine treated with onabotulinumtoxinA or calcitonin gene-related peptide monoclonal antibodies

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          Abstract

          BACKGROUND: Chronic migraine (CM) is a common neurologic disorder that imposes substantial burden on payers, patients, and society. Low rates of persistence to oral migraine preventive medications have been previously documented; however, less is known about persistence and costs associated with innovative nonoral migraine preventive medications. OBJECTIVE: To evaluate real-world persistence and costs among adults with CM treated with onabotulinumtoxinA (onabotA) or calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs). METHODS: This was a retrospective, longitudinal, observational study analyzing the IBM MarketScan Commercial and Medicare databases. The study sample included adults with CM initiating treatment with either onabotA or a CGRP mAb on or after January 1, 2018. Persistence and costs over 12 months after treatment initiation were evaluated using chi-square and Student's t-tests. Persistence to onabotA was compared with CGRP mAbs as a weighted average of the class and by individual CGRP mAbs. Mean pharmacy (acute and preventive), medical (inpatient, emergency department, and outpatient), and total costs are reported. Multivariate regression analyses were conducted to generate adjusted estimates of persistence and costs after controlling for potential confounders (age, sex, region, insurance type, number of baseline comorbidities, Charlson Comorbidity Index, and number of previously used oral migraine preventive medications). RESULTS: Of 66,303 individuals with onabotA or CGRP mAb claims, 2,697 with CM met the inclusion/exclusion criteria. In the total population, individuals were primarily female (85.5%), lived in the South (48.5%), and had a mean (SD) age of 44 (12) years, which was consistent across the onabotA and CGRP mAb cohorts. Common comorbid conditions included anxiety (23.9%), depression (18.2%), hypertension (16.5%), and sleep disorders (16.9%). After adjusting for potential confounding variables, persistence to onabotA during the 12-month follow-up period was 40.7% vs 27.8% for CGRP mAbs (odds ratio [OR] = 0.683; 95% CI = 0.604-0.768; P < 0.0001). Persistence to erenumab, fremanezumab, and galcanezumab was 25.5% (OR = 0.627; 95% CI = 0.541-0.722; P < 0.0001), 30.3% (OR = 0.746; 95% CI = 0.598-0.912; P = 0.0033), and 33.7% (OR = 0.828; 95% CI = 0.667-1.006; P = 0.058). All-cause ($18,292 vs $18,275; P = 0.9739) and migraine-related ($8,990 vs $9,341; P = 0.1374) costs were comparable between the onabotA and CGRP mAb groups. CONCLUSIONS: Among adults with CM receiving onabotA and CGRP mAbs, individuals initiating onabotA treatment had higher persistence compared with those receiving CGRP mAbs. Total all-cause and migraine-related costs over 12 months were comparable between those receiving onabotA and CGRP mAbs. DISCLOSURES: This study was sponsored by Allergan (prior to its acquisition by AbbVie), they contributed to the design and interpretation of data and the writing, reviewing, and approval of final version. Writing and editorial assistance was provided to the authors by Dennis Stancavish, MS, of Peloton Advantage, LLC, an OPEN Health company, Parsippany, NJ, and was funded by AbbVie. The opinions expressed in this article are those of the authors. The authors received no honorarium/fee or other form of financial support related to the development of this article. Dr Schwedt serves on the Board of Directors for the American Headache Society and the American Migraine Foundation. Within the prior 12 months he has received research support from Amgen, Henry Jackson Foundation, Mayo Clinic, National Institutes of Health, Patient-Centered Outcomes Research Institute, SPARK Neuro, and US Department of Defense. Within the past 12 months, he has received personal compensation for serving as a consultant or advisory board member for AbbVie, Allergan, Axsome, BioDelivery Science, Biohaven, Collegium, Eli Lilly, Ipsen, Linpharma, Lundbeck, and Satsuma. He holds stock options in Aural Analytics and Nocira. He has received royalties from UpToDate. Dr Lee and Ms Shah are employees of AbbVie and may hold AbbVie stock. Dr Gillard was an employee of AbbVie and may hold AbbVie stock. Dr Knievel has served as a consultant for AbbVie, Amgen, Eli Lilly, and Biohaven; conducted research for AbbVie, Amgen, and Eli Lilly; and is on speaker programs for AbbVie and Amgen. Dr McVige has served as a speaker and/or received research support from Allergan (now AbbVie Inc.), Alder, Amgen/Novartis, Avanir, Biohaven, Eli Lilly, Lundbeck, and Teva. Ms Wang and Ms Wu are employees of Genesis Research, which provides consulting services to AbbVie. Dr Blumenfeld, within the past 12 months, has served on advisory boards for Allergan, AbbVie, Aeon, Alder, Amgen, Axsome, BDSI, Biohaven, Impel, Lundbeck, Lilly, Novartis, Revance, Teva, Theranica, and Zosano; as a speaker for Allergan, AbbVie, Amgen, BDSI, Biohaven, Lundbeck, Lilly, and Teva; as a consultant for Allergan, AbbVie, Alder, Amgen, Biohaven, Lilly, Lundbeck, Novartis, Teva, and Theranica; and as a contributing author for Allergan, AbbVie, Amgen, Biohaven, Novartis, Lilly, and Teva. He has received grant support from AbbVie and Amgen. AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual, and trial-level data (analysis data sets), as well as other information (eg, protocols, clinical study reports, or analysis plans), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications. These clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan and execution of a Data Sharing Agreement. Data requests can be submitted at any time after approval in the United States and Europe and after acceptance of this manuscript for publication. The data will be accessible for 12 months, with possible extensions considered. For more information on the process, or to submit a request, visit the following link: https://www.abbvieclinicaltrials.com/hcp/data-sharing/.

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          Most cited references21

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          Safety and efficacy of erenumab for preventive treatment of chronic migraine: a randomised, double-blind, placebo-controlled phase 2 trial.

          The calcitonin gene-related peptide (CGRP) pathway is important in migraine pathophysiology. We assessed the efficacy and safety of erenumab, a fully human monoclonal antibody against the CGRP receptor, in patients with chronic migraine.
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            Migraine prevalence, disease burden, and the need for preventive therapy.

            1) To reassess the prevalence of migraine in the United States; 2) to assess patterns of migraine treatment in the population; and 3) to contrast current patterns of preventive treatment use with recommendations for use from an expert headache panel. A validated self-administered headache questionnaire was mailed to 120,000 US households, representative of the US population. Migraineurs were identified according to the criteria of the second edition of the International Classification of Headache Disorders. Guidelines for preventive medication use were developed by a panel of headache experts. Criteria for consider or offer prevention were based on headache frequency and impairment. We assessed 162,576 individuals aged 12 years or older. The 1-year period prevalence for migraine was 11.7% (17.1% in women and 5.6% in men). Prevalence peaked in middle life and was lower in adolescents and those older than age 60 years. Of all migraineurs, 31.3% had an attack frequency of three or more per month, and 53.7% reported severe impairment or the need for bed rest. In total, 25.7% met criteria for "offer prevention," and in an additional 13.1%, prevention should be considered. Just 13.0% reported current use of daily preventive migraine medication. Compared with previous studies, the epidemiologic profile of migraine has remained stable in the United States during the past 15 years. More than one in four migraineurs are candidates for preventive therapy, and a substantial proportion of those who might benefit from prevention do not receive it.
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              ARISE: A Phase 3 randomized trial of erenumab for episodic migraine.

              Background Calcitonin gene-related peptide plays an important role in migraine pathophysiology. Erenumab, a human monoclonal antibody that inhibits the calcitonin gene-related peptide receptor, is being evaluated for migraine prevention. Methods In this randomized, double-blind, placebo-controlled, phase 3 study, 577 adults with episodic migraine were randomized to placebo or 70 mg erenumab; 570 patients were included in efficacy analyses. Primary endpoint was change in monthly migraine days. Secondary endpoints were ≥50% reduction in monthly migraine days, change in acute migraine-specific medication treatment days, and ≥5-point reduction in Physical Impairment and Impact on Everyday Activities domain scores measured by the Migraine Physical Function Impact Diary. All endpoints assessed change from baseline at month 3. Results Patients receiving erenumab experienced -2.9 days change in monthly migraine days, compared with -1.8 days for placebo, least-squares mean (95% CI) treatment difference of -1.0 (-1.6, -0.5) ( p < 0.001). A ≥ 50% reduction in monthly migraine days was achieved by 39.7% (erenumab) and 29.5% (placebo) of patients (OR:1.59 (95% CI: 1.12, 2.27) ( p = 0.010). Migraine-specific medication treatment days were reduced by -1.2 (erenumab) and -0.6 (placebo) days, a treatment difference of -0.6 (-1.0, -0.2) ( p = 0.002). The ≥5-point reduction rates in Migraine Physical Function Impact Diary - Physical Impairment were 33.0% and 27.1% (OR:1.33 (0.92, 1.90) ( p = 0.13) and in Migraine Physical Function Impact Diary - Everyday Activities were 40.4% and 35.8% (OR:1.22 (0.87, 1.71) ( p = 0.26). Safety and adverse event profiles of erenumab were similar to placebo. Most frequent adverse events were upper respiratory tract infection, injection site pain, and nasopharyngitis. Conclusions As a preventive treatment of episodic migraine, erenumab at a dosage of 70 mg monthly significantly reduced migraine frequency and acute migraine-specific medication use. (Funded by Amgen). Trial registration ClinicalTrials.gov, NCT02483585.
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                Author and article information

                Journal
                Journal of Managed Care & Specialty Pharmacy
                JMCP
                Academy of Managed Care Pharmacy
                2376-0540
                2376-1032
                October 2023
                October 2023
                : 29
                : 10
                : 1119-1128
                Affiliations
                [1 ]Mayo Clinic, Scottsdale, AZ.
                [2 ]AbbVie, Irvine, CA.
                [3 ]Barrow Neurological Institute, Phoenix, AZ.
                [4 ]DENT Neurologic Institute, Amherst, NY.
                [5 ]Genesis Research LLC, Hoboken, NJ.
                [6 ]AbbVie, Madison, NJ.
                [7 ]The Los Angeles Headache Center, CA.
                [8 ]The San Diego Headache Center, CA.
                Article
                10.18553/jmcp.2023.29.10.1119
                10541629
                37776119
                ecb8e1a1-fd9a-4d95-b6d4-2a24a0d2d53a
                © 2023
                History

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