{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T14:35:52Z","timestamp":1793111752288,"version":"4.5.0"},"reference-count":47,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2006,11,29]],"date-time":"2006-11-29T00:00:00Z","timestamp":1164758400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Headache"],"published-print":{"date-parts":[[2007,4]]},"abstract":"<jats:p>\n                    Objective.\u2014This exploratory trial evaluated the safety and efficacy of multiple treatments of botulinum toxin type A (BoNTA; BOTOX\n                    <jats:sup>\u00ae<\/jats:sup>\n                    , Allergan, Inc., Irvine, CA, USA) as prophylactic treatment of episodic migraine headaches.\n                  <\/jats:p>\n                  <jats:p>Design and Methods.\u2014This was an 11\u2010month randomized, double\u2010blind, placebo\u2010controlled, exploratory study. Patients were screened during a 30\u2010day baseline period, and eligible patients with 4 or more migraine episodes and \u226415 headache days entered a single\u2010blind 30\u2010day placebo run\u2010in period. Patients were classified as placebo nonresponders (PNR) if they had at least 4 moderate\u2010to\u2010severe migraine episodes and did not experience at least a 50% decrease from baseline in the frequency of migraine episodes following their placebo treatment. All other subjects were classified as placebo responders (PR). Patients were randomized within each stratum (PNR, PR) to 3 treatments with BoNTA (110 to 260 U of BoNTA per treatment cycle) or placebo at 90\u2010day intervals using a modified follow\u2010the\u2010pain treatment paradigm. The primary efficacy outcome measure was the mean change from baseline in the frequency of migraine episodes for the 30 days prior to day 180 in the PNR group. Secondary efficacy measures included the proportion of patients with a decrease from baseline of 50% or more migraine episodes per 30\u2010day period. Patients were allowed to take concomitant acute and prophylactic headache medications. Adverse events were reported.<\/jats:p>\n                  <jats:p>\n                    Results.\u2014A total of 809 patients were screened and 369 patients (89.2% female; mean age, 45 years; range, 20 to 65 years) entered the placebo run\u2010in period and were subsequently randomized to BoNTA or placebo. The mean total dose of BoNTA was 190.5 units (U) (range, 110 U to 260 U). The predetermined primary efficacy endpoint was not met. Substantial mean improvements of 2.4 and 2.2 fewer migraine episodes per month at day 180 in the PNR stratum treated with BoNTA and placebo, respectively, were observed (\n                    <jats:italic>P<\/jats:italic>\n                    &gt; .999). From day 180 through the end of the study (day 270) at least 50% of all patients in each treatment group had a decrease from baseline of 50% or more migraine episodes per 30\u2010day period. However, in the group of patients with \u226512 headache days at baseline (and \u226415 headache days), BoNTA patients experienced a mean change from baseline of \u22124.0 headache episodes at day 180 compared with \u22121.9 headache episodes in the placebo group (\n                    <jats:italic>P<\/jats:italic>\n                    = .048). The majority of treatment\u2010related adverse events were transient and mild to moderate in severity. Only 7 patients (1.9%) discontinued the study due to adverse events (6 BoNTA, 1 placebo).\n                  <\/jats:p>\n                  <jats:p>Conclusion.\u2014There were no statistically significant between\u2010group differences in the mean change from baseline in the frequency of migraine episodes per 30\u2010day period. There were substantial, sustained improvements during the course of the study in all groups. Multiple treatments with BoNTA were shown to be safe and well tolerated over an active treatment period lasting 9 months.<\/jats:p>","DOI":"10.1111\/j.1526-4610.2006.00624.x","type":"journal-article","created":{"date-parts":[[2006,11,29]],"date-time":"2006-11-29T08:27:28Z","timestamp":1164788848000},"page":"486-499","source":"Crossref","is-referenced-by-count":96,"title":["Botulinum Toxin Type A Prophylactic Treatment of Episodic Migraine: A Randomized, Double\u2010Blind, Placebo\u2010Controlled Exploratory Study"],"prefix":"10.1111","volume":"47","author":[{"given":"Sheena K.","family":"Aurora","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marek","family":"Gawel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan L.","family":"Brandes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suriani","family":"Pokta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda M.","family":"VanDenburgh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the BOTOX North American Episodic Migraine Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,11,29]]},"reference":[{"key":"e_1_2_8_2_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1526-4610.2001.041007646.x"},{"key":"e_1_2_8_3_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1526-4610.2001.041007646.x"},{"key":"e_1_2_8_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)15440-8"},{"key":"e_1_2_8_5_2","unstructured":"World Health Organization.Headache disorders and public health: Education and management implications. 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