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. 2023 Dec 12;101(24):e2560-e2570.
doi: 10.1212/WNL.0000000000207964. Epub 2023 Nov 22.

Simultaneous Comparisons of 25 Acute Migraine Medications Based on 10 Million Users' Self-Reported Records From a Smartphone Application

Chia-Chun Chiang  1 , Xuemin Fang  1 , Zsolt Horvath  1 , Francois Cadiou  1 , Alexandre Urani  1 , Weijie Poh  1 , Hiroto Narimatsu  1 , Yu Cheng  1 , David W Dodick  1
Affiliations

Simultaneous Comparisons of 25 Acute Migraine Medications Based on 10 Million Users' Self-Reported Records From a Smartphone Application

Chia-Chun Chiang et al. Neurology. .

Erratum in

  • Corrections to Received Date Information.
    [No authors listed] [No authors listed] Neurology. 2024 Jul 9;103(1):e209596. doi: 10.1212/WNL.0000000000209596. Epub 2024 Jun 3. Neurology. 2024. PMID: 38830175 Free PMC article. No abstract available.

Abstract

Background and objectives: Many acute treatment options exist for migraine. However, large-scale, head-to-head comparisons of treatment effectiveness from real-world patient experience reports are lacking.

Methods: This is a retrospective analysis of 10,842,795 migraine attack records extracted from an e-diary smartphone application between June 30, 2014, and July 2, 2020. We analyzed 25 acute medications among 7 classes-acetaminophen, nonsteroid anti-inflammatory drugs (NSAIDs), triptans, combination analgesics, ergots, antiemetics, and opioids. Gepants and ditan were not included in this analysis. Different doses and formulations of each medication, according to the generic names, were combined in this analysis. We used a 2-level nested logistic regression model to analyze the odds ratio (OR) of treatment effectiveness of each medication by adjusting concurrent medications and the covariance within the same user. Subgroup analyses were conducted for users in the United States, the United Kingdom, and Canada.

Results: Our final analysis included 4,777,524 medication-outcome pairs from 3,119,517 migraine attacks among 278,006 users. Triptans (mean OR 4.8), ergots (mean OR 3.02), and antiemetics (mean OR 2.67) were the top 3 classes of medications with the highest effectiveness, followed by opioids (mean OR 2.49), NSAIDs (other than ibuprofen, mean OR 1.94), combination analgesics (acetaminophen/acetylsalicylic acid/caffeine) (OR 1.69, 95% CI 1.67-1.71), others (OR 1.49, 95% CI 1.47-1.50), and acetaminophen (OR 0.83, 95% CI 0.83-0.84), using ibuprofen as the reference. Individual medications with the highest ORs were eletriptan (OR 6.1, 95% CI 6.0-6.3), zolmitriptan (OR 5.7, 95% CI 5.6-5.8), and sumatriptan (OR 5.2, 95% CI 5.2-5.3). The ORs of acetaminophen, NSAIDS, combination analgesics, and opioids were mostly around or less than 1, suggesting similar or lower reported effectiveness compared with ibuprofen. The ORs for 24 medications, except that of acetylsalicylic acid, achieved statistical significance with p < 0.0001, and our nested logistic regression model achieved an area under the curve (AUC) of 0.849. Country-specific subgroup analyses revealed similar ORs of each medication and AUC (United States 0.849, United Kingdom 0.864, and Canada 0.842), demonstrating the robustness of our analysis.

Discussion: Using a big data approach, we analyzed patient-generated real-time records of 10 million migraine attacks and conducted simultaneous head-to-head comparisons of 25 acute migraine medications. Our findings that triptans, ergots, and antiemetics are the most effective classes of medications align with the guideline recommendations and offer generalizable insights to complement clinical practice.

Classification of evidence: This study provides Class IV evidence that for patients with migraine, selected acute medications (e.g., triptans, ergots, antiemetics) are associated with higher odds of user-rated positive response than ibuprofen.

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Conflict of interest statement

The following authors have no financial disclosure: X. Fang, H. Narimatsu, and Y. Cheng. C.-C. Chiang reports the following disclosures—consulting: Satsuma, eNeura. Z. Horvath, F. Cadiou, A. Urani, W. Poh were employees of Healint Pte. Ltd. D.W. Dodick reports the following disclosures—consulting: Amgen, Atria, Cerecin, Cooltech, Ctrl M, Allergan, Abbvie, Biohaven, GSK, Lundbeck, Eli Lilly, Novartis, Impel, Satsuma, Theranica, WL Gore, Genentech, Nocira, Perfood, Praxis, Pfizer, AYYA Biosciences, Revance. Honoraria: American Academy of Neurology, Headache Cooperative of the Pacific, MF Med Ed Research, Biopharm Communications, CEA Group Holding Company (Clinical Education Alliance LLC), Teva (speaking), Amgen (speaking), Eli Lilly (speaking), Lundbeck (speaking), Vector psychometric Group, Clinical Care Solutions, CME Outfitters, Curry Rockefeller Group, DeepBench, Global Access Meetings, KLJ Associates, Academy for Continued Healthcare Learning, Majallin LLC, Medlogix Communications, Medica Communications LLC, MJH Lifesciences, Miller Medical Communications, Synapse, WebMD Health/Medscape, Wolters Kluwer, Oxford University Press, Cambridge University Press. Nonprofit board membership: American Brain Foundation, American Migraine Foundation, ONE Neurology, Precon Health Foundation, International Headache Society Global Patient Advocacy Coalition, Atria Health Collaborative, Domestic Violence HOPE Foundation/Panfila. Research Support: Department of Defense, NIH, Henry Jackson Foundation, Sperling Foundation, American Migraine Foundation, Patient-Centered Outcomes Research Institute (PCORI). Stock Options/Shareholder/Patents/Board of Directors: Ctrl M (options), Aural analytics (options), ExSano (options), Palion (options), Healint (options), Theranica (options), Second Opinion/Mobile Health (options), Epien (options/board), Nocira (options), Matterhorn (shares/board), Ontologics (shares/board), King-Devick Technologies (options/board), Precon Health (options/board), AYYA Biosciences (options), Axon Therapeutics (options/board), Cephalgia Group (options/board), Atria Health (options/employee). Patent 17189376.1-1466:vTitle: Botulinum Toxin Dosage Regimen for Chronic Migraine Prophylaxis. Go to Neurology.org/N for full disclosures.

Figures

Figure 1
Figure 1. Flow Diagram of Migraine Attack Records Analyzed According to the Inclusion and Exclusion Criteria
A total of 10,842,795 migraine attack records were extracted from the database. Our final analysis included 4,777,524 unique medication-outcome pairs from 3,119,517 migraine attacks recorded from 278,006 users.
Figure 2
Figure 2. Ratio of Positive Treatment Outcomes (% of Helpful) Among All Reported Outcomes per Medication
Figure 3
Figure 3. Forest Plot of the ORs Representing Comparison of Patient-Reported Treatment Effectiveness of 25 Acute Migraine Medications
NSAID = nonsteroid anti-inflammatory drug; OR = odds ratio; OTC = over-the-counter.
Figure 4
Figure 4. Odds Ratios Correlation and ROC Analysis of Regression Model
(A) The odds ratios obtained from the nested logistic regression model were highly correlated with the percentages of “Helpful” reported by users with an R2 of 90%. (B) The ROC curve of the logistic regression model has an AUC of 0.849, suggesting a good fit for the model. AUC = area under the curve; NSAID = nonsteroid anti-inflammatory drug; OTC = over-the-counter; ROC = receiver operating characteristic.
Figure 5
Figure 5. Forest Plot of the Odds Ratios and 95% CI of Medications From Canada (CA), the United Kingdom (UK), and the United States (USA) in Country-Specific Analysis
See this image and copyright information in PMC

Comment in

References

    1. GBD 2016 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet. 2017;390(10100):1211-1259. doi:10.1016/s0140-6736(17)32154-2 - DOI - PMC - PubMed
    1. GBD 2016 Neurology Collaborators. Global, regional, and national burden of neurological disorders, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2019;18(5):459-480. doi:10.1016/s1474-4422(18)30499-x - DOI - PMC - PubMed
    1. Ashina M, Buse DC, Ashina H, et al. . Migraine: integrated approaches to clinical management and emerging treatments. Lancet. 2021;397(10283):1505-1518. doi:10.1016/s0140-6736(20)32342-4 - DOI - PubMed
    1. VanderPluym JH, Halker Singh RB, Urtecho M, et al. . Acute treatments for episodic migraine in adults: a systematic review and meta-analysis. JAMA. 2021;325(23):2357-2369. doi:10.1001/jama.2021.7939 - DOI - PMC - PubMed
    1. Ailani J, Burch RC, Robbins MS; Board of Directors of the American Headache Society. The American Headache Society consensus statement: update on integrating new migraine treatments into clinical practice. Headache. 2021;61(7):1021-1039. doi:10.1111/head.14153 - DOI - PubMed

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