Comparative Analysis of Real–World Acute Prescription Migraine Therapy Outcomes: Insights from the HeAD–US Study

Comparative Analysis of Real World Acute Prescription Migraine Therapy Outcomes: Insights from the HeAD US Study | medRxiv /* */ /* */ <!-- <!-- /*! * yepnope1.5.4 * (c) WTFPL, GPLv2 */ (function(a,b,c){function d(a){return"[object Function]"==o.call(a)}function e(a){return"string"==typeof a}function f(){}function g(a){return!a||"loaded"==a||"complete"==a||"uninitialized"==a}function h(){var a=p.shift();q=1,a?a.t?m(function(){("c"==a.t?B.injectCss:B.injectJs)(a.s,0,a.a,a.x,a.e,1)},0):(a(),h()):q=0}function i(a,c,d,e,f,i,j){function k(b){if(!o&&g(l.readyState)&&(u.r=o=1,!q&&h(),l.onload=l.onreadystatechange=null,b)){"img"!=a&&m(function(){t.removeChild(l)},50);for(var d in y[c])y[c].hasOwnProperty(d)&&y[c][d].onload()}}var j=j||B.errorTimeout,l=b.createElement(a),o=0,r=0,u={t:d,s:c,e:f,a:i,x:j};1===y[c]&&(r=1,y[c]=[]),"object"==a?l.data=c:(l.src=c,l.type=a),l.width=l.height="0",l.onerror=l.onload=l.onreadystatechange=function(){k.call(this,r)},p.splice(e,0,u),"img"!=a&&(r||2===y[c]?(t.insertBefore(l,s?null:n),m(k,j)):y[c].push(l))}function j(a,b,c,d,f){return q=0,b=b||"j",e(a)?i("c"==b?v:u,a,b,this.i++,c,d,f):(p.splice(this.i++,0,a),1==p.length&&h()),this}function k(){var a=B;return a.loader={load:j,i:0},a}var l=b.documentElement,m=a.setTimeout,n=b.getElementsByTagName("script")[0],o={}.toString,p=[],q=0,r="MozAppearance"in l.style,s=r&&!!b.createRange().compareNode,t=s?l:n.parentNode,l=a.opera&&"[object Opera]"==o.call(a.opera),l=!!b.attachEvent&&!l,u=r?"object":l?"script":"img",v=l?"script":u,w=Array.isArray||function(a){return"[object Array]"==o.call(a)},x=[],y={},z={timeout:function(a,b){return b.length&&(a.timeout=b[0]),a}},A,B;B=function(a){function b(a){var a=a.split("!"),b=x.length,c=a.pop(),d=a.length,c={url:c,origUrl:c,prefixes:a},e,f,g;for(f=0;f<d;f++)g=a[f].split("="),(e=z[g.shift()])&&(c=e(c,g));for(f=0;f<b;f++)c=x[f](c);return c}function g(a,e,f,g,h){var i=b(a),j=i.autoCallback;i.url.split(".").pop().split("?").shift(),i.bypass||(e&&(e=d(e)?e:e[a]||e[g]||e[a.split("/").pop().split("?")[0]]),i.instead?i.instead(a,e,f,g,h):(y[i.url]?i.noexec=!0:y[i.url]=1,f.load(i.url,i.forceCSS||!i.forceJS&&"css"==i.url.split(".").pop().split("?").shift()?"c":c,i.noexec,i.attrs,i.timeout),(d(e)||d(j))&&f.load(function(){k(),e&&e(i.origUrl,h,g),j&&j(i.origUrl,h,g),y[i.url]=2})))}function h(a,b){function c(a,c){if(a){if(e(a))c||(j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}),g(a,j,b,0,h);else if(Object(a)===a)for(n in m=function(){var b=0,c;for(c in a)a.hasOwnProperty(c)&&b++;return b}(),a)a.hasOwnProperty(n)&&(!c&&!--m&&(d(j)?j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}:j[n]=function(a){return function(){var b=[].slice.call(arguments);a&&a.apply(this,b),l()}}(k[n])),g(a[n],j,b,n,h))}else!c&&l()}var h=!!a.test,i=a.load||a.both,j=a.callback||f,k=j,l=a.complete||f,m,n;c(h?a.yep:a.nope,!!i),i&&c(i)}var i,j,l=this.yepnope.loader;if(e(a))g(a,0,l,0);else if(w(a))for(i=0;i (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0];var j=d.createElement(s);var dl=l!='dataLayer'?'&l='+l:'';j.src='//www.googletagmanager.com/gtm.js?id='+i+dl;j.type='text/javascript';j.async=true;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-P4HH5NV'); Skip to main content Home About Submit ALERTS / RSS Search for this keyword Advanced Search Comparative Analysis of Real World Acute Prescription Migraine Therapy Outcomes: Insights from the HeAD US Study Devin Teichrow , View ORCID Profile Babak Khorsand , Kristina M Fanning , Alexandre Urani , François Cadiou , Richard B Lipton , Ali Ezzati doi: https://doi.org/10.1101/2025.09.18.25336093 Devin Teichrow 1 Department of Neurology, University of California, Irvine (UCI), Irvine, USA.; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Babak Khorsand 2 University of California, Irvine; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Babak Khorsand Kristina M Fanning 3 MIST Research; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Alexandre Urani 4 APTAR LLC, USA; Find this author on Google Scholar Find this author on PubMed Search for this author on this site François Cadiou 4 APTAR LLC, USA; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Richard B Lipton 5 Department of Neurology, Albert Einstein College of Medicine and Montefiore Medical center, Bronx, NY, USA Find this author on Google Scholar Find this author on PubMed Search for this author on this site Ali Ezzati 2 University of California, Irvine; Find this author on Google Scholar Find this author on PubMed Search for this author on this site For correspondence: ezzatia{at}hs.uci.edu Abstract Info/History Metrics Data/Code Preview PDF Abstract Background: Triptans have long served as the primary acute migraine treatment, while gepants represent a newer, non vasoconstrictive alternative. Although clinical trials have explored efficacy within each class, head to head studies are lacking, and real world data on optimal treatment response and patient level predictors of outcomes remain limited. We leverage baseline data from the HeAD US study to conduct real world comparisons of triptans and gepants for 2 hour pain freedom (2hPF) and 24 hour pain relief (24hPR), and to identify demographic, clinical, and treatment related predictors of these outcomes. Methods: Head US is a survey conducted among users of the Migraine Buddy application. Eligible participants completed the survey, met ICHD 3 criteria for migraine and reported using acute monotherapy with a gepants (n = 570) or triptan (n = 1018). Primary outcomes, 2hPF and 24hPR post treatment, were assessed using the Migraine Treatment Optimization Questionnaire (mTOQ 6). Potential predictors included demographic factors, clinical measures, and treatment related factors. Logistic regression models were applied to complete case data, with pairwise comparisons estimated via marginal means. Results: Among 1,588 eligible respondents 570 used gepants and 1,018 used a triptan. Mean age was 43.35 years (SD = 13.04), and 94.8% were female. Gepant users demonstrated 39% higher odds of achieving 24hPR compared to triptan users (OR = 1.39, 95% CI: 1.11,1.74) though there were no significant differences the the 2hPF outcome. Reduced odds of adequate 2hPF were associated with higher migraine symptom severity, high-frequency episodic migraine, chronic migraine, severe pain intensity, and severe migraine disability. Odds of achieving 24hPR were reduced in those with higher migraine symptom severity, higher attack frequency, severe migraine disability, and preventive medication use. Predictors of treatment response were similar in the pooled sample and in those using gepants and in those using triptans. Conclusion: In this large, real-world cohort, triptans and gepants showed comparable effectiveness for 2hPF, but gepants demonstrated a significant advantage for 24hPR. Clinical features such as symptom severity, headache frequency, disability, and comorbid treatment burden were important predictors of treatment response. These findings support the need for larger, head to head clinical trials definitively comparing these medication classes for migraine management and may inform personalized selection of acute migraine therapies in clinical practice. Competing Interest Statement Ali Ezzati receives research support from the following sources: National Institute of Health (NIA K23 AG063993; NIA-1R01AG080635-01A1), the Alzheimer's Association (SG-24-988,292), Cure Alzheimer's Fund, and Amgen investigator-initiated studies. Kristina M. Fanning is the managing director of MIST Research, which received grants from the National Headache Foundation in addition to funding from Allergan, Amgen, Dr. Reddy's Laboratories/Promius, and Eli Lilly via collaboration with Vedanta Research. Alexandre Urani and Francois Cadiou are employees of APTAR, which is the parent company of Migraine Buddy. Richard B. Lipton receives research support from the NIH and the FDA as well as the National Headache Foundation and the Marx Foundation. He serves on the editorial board of Neurology, as senior advisor to Headache, and as associate editor to Cephalalgia. He has reviewed for the NIA and NINDS; holds stock options in Axon, Biohaven Holdings, CoolTech, and Manistee; serves as consultant or advisory board member or has received honoraria from Abbvie (Allergan), American Academy of Neurology, American Headache Society, Amgen, Avanir, Biohaven, Biovision, Boston Scientific, CoolTech, Dr. Reddy's (Promius), Electrocore, Eli Lilly, eNeura Therapeutics, GlaxoSmithKline, Grifols, Lundbeck (Alder), Pfizer, Teva, Trigemina, Vector, and Vedanta. He receives royalties from Wolff's Headache 7th and 8th Edition, Oxford Press University, 2009, Wiley and Informa. Devin Teichrow declares no conflicts of interest. Funding Statement This study did not receive any funding. Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: reviewed and approved by the Advarra, Inc. Institutional Review Board (CIRBI Protocol #Pro00072897). The secondary analysis described in the manuscript was reviewed and approved by the Institutional Review Board of the University of California, Irvine (IRB # 5459) I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Footnotes Cleaning up tables 3 and 4 for clarity. Data Availability Data available upon reasonable request. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. View the discussion thread. Back to top Previous Next Posted September 19, 2025. Download PDF Data/Code Email Thank you for your interest in spreading the word about medRxiv. 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Share Comparative Analysis of Real World Acute Prescription Migraine Therapy Outcomes: Insights from the HeAD US Study Devin Teichrow , Babak Khorsand , Kristina M Fanning , Alexandre Urani , François Cadiou , Richard B Lipton , Ali Ezzati medRxiv 2025.09.18.25336093; doi: https://doi.org/10.1101/2025.09.18.25336093 Share This Article: Copy Citation Tools Comparative Analysis of Real World Acute Prescription Migraine Therapy Outcomes: Insights from the HeAD US Study Devin Teichrow , Babak Khorsand , Kristina M Fanning , Alexandre Urani , François Cadiou , Richard B Lipton , Ali Ezzati medRxiv 2025.09.18.25336093; doi: https://doi.org/10.1101/2025.09.18.25336093 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Area Neurology Subject Areas All Articles Addiction Medicine (568) Allergy and Immunology (863) Anesthesia (300) Cardiovascular Medicine (4435) Dentistry and Oral Medicine (444) Dermatology (382) Emergency Medicine (608) Endocrinology (including Diabetes Mellitus and Metabolic Disease) (1509) Epidemiology (15229) Forensic Medicine (30) Gastroenterology (1124) Genetic and Genomic Medicine (6600) Geriatric Medicine (668) Health Economics (997) Health Informatics (4538) Health Policy (1368) Health Systems and Quality Improvement (1613) Hematology (541) HIV/AIDS (1264) Infectious Diseases (except HIV/AIDS) (15916) Intensive Care and Critical Care Medicine (1103) Medical Education (623) Medical Ethics (146) Nephrology (667) Neurology (6599) Nursing (346) Nutrition (998) Obstetrics and Gynecology (1144) Occupational and Environmental Health (957) Oncology (3333) Ophthalmology (974) Orthopedics (369) Otolaryngology (420) Pain Medicine (436) Palliative Medicine (130) Pathology (663) Pediatrics (1693) Pharmacology and Therapeutics (691) Primary Care Research (711) Psychiatry and Clinical Psychology (5447) Public and Global Health (9232) Radiology and Imaging (2198) Rehabilitation Medicine and Physical Therapy (1370) Respiratory Medicine (1196) Rheumatology (593) Sexual and Reproductive Health (712) Sports Medicine (530) Surgery (712) Toxicology (99) Transplantation (289) Urology (265) (function(){function c(){var b=a.contentDocument||a.contentWindow.document;if(b){var d=b.createElement('script');d.innerHTML="window.__CF$cv$params={r:'a00dd3478df9ec04',t:'MTc3OTY0MTY5OA=='};var a=document.createElement('script');a.src='/cdn-cgi/challenge-platform/scripts/jsd/main.js';document.getElementsByTagName('head')[0].appendChild(a);";b.getElementsByTagName('head')[0].appendChild(d)}}if(document.body){var a=document.createElement('iframe');a.height=1;a.width=1;a.style.position='absolute';a.style.top=0;a.style.left=0;a.style.border='none';a.style.visibility='hidden';document.body.appendChild(a);if('loading'!==document.readyState)c();else if(window.addEventListener)document.addEventListener('DOMContentLoaded',c);else{var e=document.onreadystatechange||function(){};document.onreadystatechange=function(b){e(b);'loading'!==document.readyState&&(document.onreadystatechange=e,c())}}}})();