{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T22:15:20Z","timestamp":1790115320855,"version":"4.0.1"},"reference-count":51,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,2,9]],"date-time":"2020-02-09T00:00:00Z","timestamp":1581206400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007819","name":"Allergan","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007819","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["headachejournal.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Headache"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>As a post\u2010approval commitment, this dose\u2010ranging study was undertaken to evaluate efficacy and safety of onabotulinumtoxinA in adolescents.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>In adolescents, migraine is often undiagnosed or misdiagnosed and can present unique management challenges. OnabotulinumtoxinA was approved for prevention of chronic migraine (CM) in adults in 2010.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This multicenter, double\u2010blind, parallel\u2010group, randomized trial assessed a single treatment of onabotulinumtoxinA (155\u00a0U or 74\u00a0U) vs placebo (intramuscular saline) administered via the recommended fixed\u2010dose fixed site paradigm in adolescents with CM aged 12 to &lt;18\u00a0years. The primary efficacy measure was change in frequency of headache days from baseline at week 12; other measures included change in frequency of headache days at weeks 4 and 8 and change in frequency of severe headache days. Safety and tolerability were assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of 125 randomized patients (onabotulinumtoxinA 155\u00a0U, n\u00a0=\u00a045; onabotulinumtoxinA 74\u00a0U, n\u00a0=\u00a043; placebo, n\u00a0=\u00a037), all were included in the primary efficacy analysis, and\u00a0115 (92.0%) completed the study. Lack of efficacy was the primary reason for discontinuing (n\u00a0=\u00a04; 3.2%); no patients discontinued because of adverse events. All treatments reduced frequency of headache days at week 12, with no significant differences between treatments. The mean (95% confidence interval) changes from baseline in the frequency of headache days during the 28\u2010day period ending at week 12 (primary endpoint) were \u22126.3 (\u22128.5, \u22124.2), \u22126.4 (\u22128.8, \u22124.0), and \u22126.8 (\u22129.6, \u22124.1) days in the onabotulinumtoxinA 155\u00a0U, onabotulinumtoxinA 74\u00a0U, and placebo groups, respectively (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0\u2265\u00a0.474). All treatments reduced frequency of severe headache days and were well\u2010tolerated; serious adverse events (n\u00a0=\u00a03) were considered unrelated to treatment and resolved without sequelae. The most commonly reported treatment\u2010emergent adverse events were neck pain (n\u00a0=\u00a08), upper respiratory tract infection (n\u00a0=\u00a07), migraine, and nasopharyngitis (n\u00a0=\u00a05 each).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Although this study did not meet its efficacy endpoints, onabotulinumtoxinA was well tolerated in this adolescent population. Given previous data demonstrating the benefits of onabotulinumtoxinA in adults with CM, additional studies with design modifications, including adequate statistical power, to assess the efficacy of multiple treatment cycles of onabotulinumtoxinA for CM prevention in adolescents may be informative.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/head.13754","type":"journal-article","created":{"date-parts":[[2020,2,9]],"date-time":"2020-02-09T23:03:12Z","timestamp":1581289392000},"page":"564-575","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["A Randomized Trial to Evaluate OnabotulinumtoxinA for Prevention of Headaches in Adolescents With Chronic Migraine"],"prefix":"10.1111","volume":"60","author":[{"given":"Paul K.","family":"Winner","sequence":"first","affiliation":[{"name":"Palm Beach Headache Center Premiere Research Institute@Palm Beach Neurology West Palm Beach FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marielle","family":"Kabbouche","sequence":"additional","affiliation":[{"name":"Cincinnati Children\u2019s Hospital Medical Centre Cincinnati OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcy","family":"Yonker","sequence":"additional","affiliation":[{"name":"University of Colorado School of Medicine\/Children\u2019s Hospital Aurora CO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Wangsadipura","sequence":"additional","affiliation":[{"name":"Allergan plc Irvine CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arlene","family":"Lum","sequence":"additional","affiliation":[{"name":"Allergan plc Irvine CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitchell F.","family":"Brin","sequence":"additional","affiliation":[{"name":"Allergan plc Irvine CA USA"},{"name":"University of California Irvine CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,2,9]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-8749.2010.03793.x"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)32154-2"},{"key":"e_1_2_9_4_1","first-page":"2S","article-title":"Pediatric migraine: Recognition and treatment","volume":"105","author":"Hershey AD","year":"2005","journal-title":"J Am Osteopath Assoc"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0035-3787(05)85119-7"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/0333102417738202"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11916-016-0538-z"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1526-4610.2011.01885.x"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1526-4610.2012.02223.x"},{"key":"e_1_2_9_10_1","first-page":"326","article-title":"Treatment of pediatric migraine","volume":"17","author":"O'Brien HL","year":"2015","journal-title":"Curr Treat Options Neurol"},{"key":"e_1_2_9_11_1","volume-title":"Trokendi XR [Package Insert]","year":"2018"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1526-4610.2010.01678.x"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1526-4610.2011.01990.x"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/JNN.0b013e3181aaa98f"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11910-012-0251-1"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2010.06.001"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1526-4610.2010.01766.x"},{"key":"e_1_2_9_18_1","volume-title":"Botox [Package Insert]","year":"2019"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.57.11.2034"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0032-1329612"},{"key":"e_1_2_9_21_1","first-page":"39","article-title":"Botulinum toxin injections for chronic migraine in adolescents \u2013 An early therapeutic option in the transition from neuropaediatrics to neurology","volume":"82","author":"Bernhard MK","year":"2014","journal-title":"Fortschr Neurol Psychiatr"},{"key":"e_1_2_9_22_1","first-page":"17","volume-title":"5th European Headache and Migraine Trust International Congress","author":"Choi Y","year":"2016"},{"key":"e_1_2_9_23_1","unstructured":"M\u2010D Calderon W Wu M Ma A longitudinal evaluation of the effectiveness of Botox\u00ae in pediatric patients experiencing migraines: A five\u2010year retrospective study"},{"key":"e_1_2_9_24_1","first-page":"S299","article-title":"Is less more? 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