{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T10:52:20Z","timestamp":1790419940937,"version":"4.1.0"},"reference-count":31,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,7,4]],"date-time":"2023-07-04T00:00:00Z","timestamp":1688428800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis Care &amp;amp; Research"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To evaluate the efficacy and safety of TNX\u2010102 SL, a once\u2010nightly sublingual formulation of cyclobenzaprine, in reducing pain in patients with fibromyalgia (FM).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>RELIEF was a double\u2010blind, randomized, placebo\u2010controlled trial. Overall, 503 patients received TNX\u2010102 SL 2.8 mg for 2\u2009weeks, followed by 5.6 mg for 12\u2009weeks (248 patients), or matching placebo (255 patients). The primary end point was change from baseline at week 14 in the weekly average of daily pain scores. Secondary end points included Patient Global Impression of Change (PGIC) scores, Fibromyalgia Impact Questionnaire Revised (FIQR) scores, Patient\u2010Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance and Fatigue scores, and daily sleep quality. Safety was assessed by adverse event (AE) reporting.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Reduction in daily pain from baseline at week 14 was significantly greater with TNX\u2010102 SL (least squares [LS] mean change \u20131.9 [95% confidence interval (95% CI) \u22122.1, \u22121.7]) versus placebo (LS mean change \u22121.5 [95% CI \u22121.7, \u22121.3]; <jats:italic>P<\/jats:italic> =\u20090.01). TNX\u2010102 SL was not associated with significant improvement in PGIC at week 14 but was associated with improvements in FIQR scores, PROMIS scores, and daily sleep quality. Overall, 59.7% of patients receiving TNX\u2010102 SL and 46.3% receiving placebo reported treatment\u2010emergent AEs; the most common were oral hypoesthesia (17.3% with TNX\u2010102 SL versus 0.4% with placebo), oral paresthesia (5.6% versus 0.4%, respectively), and product taste abnormal (4.4% versus 0.4%, respectively).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In this phase III, randomized, controlled trial of patients with FM, treatment with TNX\u2010102 SL was associated with significant reductions in daily pain and was safe and well tolerated.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acr.25142","type":"journal-article","created":{"date-parts":[[2023,5,11]],"date-time":"2023-05-11T05:16:53Z","timestamp":1683782213000},"page":"2359-2368","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Efficacy and Safety of Sublingual Cyclobenzaprine for the Treatment of Fibromyalgia: Results From a Randomized, <scp>Double\u2010Blind, Placebo\u2010Controlled<\/scp> Trial"],"prefix":"10.1002","volume":"75","author":[{"given":"Seth","family":"Lederman","sequence":"first","affiliation":[{"name":"Tonix Pharmaceuticals, Inc.  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Chatham New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,7,4]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr.20140"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semarthrit.2016.08.012"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2018.10.008"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11916-013-0356-5"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr.21896"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780380104"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40520-014-0238-7"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychores.2017.03.011"},{"key":"e_1_2_9_10_1","volume-title":"Treatments for fibromyalgia in adult subgroups [review]","author":"Forte ML","year":"2015"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/1472-6963-10-102"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.psy.41.2.104"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.20076"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2016-209724"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780370106"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780311210"},{"key":"e_1_2_9_17_1","unstructured":"SullivanG KiuR StillwellH et al.Steady\u2010state pharmacokinetic properties of a sublingual formulation of cyclobenzaprine (CBP) HCl (TNX\u2010102 SL*): comparison to simulations of oral immediate release CBP [poster]. Presented at the American Society of Clinical Psychopharmacology; 2019 May 28\u201331; Scottsdale Arizona."},{"key":"e_1_2_9_18_1","unstructured":"DaughertyB GershellL LedermanS.Cyclobenzaprine (CBP) and its major metabolite norcyclobenzaprine (nCBP) are potent antagonists of human serotonin receptor 2a (5HT2a) histamine receptor H\u20101 and alpha\u2010adrenergic receptors: mechanistic and safety implications for treating fibromyalgia syndrome by improving sleep quality [abstract no. 960]. Presented at the ACR\/ARHP Annual Meeting; 2012 November 9\u201314; Washington DC. URL:https:\/\/acrabstracts.org\/abstract\/cyclobenzaprine\u2010cbp\u2010and\u2010its\u2010major\u2010metabolite\u2010norcyclobenzaprine\u2010ncbp\u2010are\u2010potent\u2010antagonists\u2010of\u2010human\u2010serotonin\u2010receptor\u20102a\u20105ht2a\u2010histamine\u2010receptor\u2010h\u20101\u2010and\u2010a\u2010adrenergic\u2010receptors\u2010mechanistic\u2010a\/."},{"key":"e_1_2_9_19_1","unstructured":"DaughertyB SullivanG GershellL et al.Serotonin receptor profiles of bedtime pharmacotherapies targeting posttraumatic stress disorder (PTSD) [abstract no. 728]. Presented at the Society of Biological Psychiatry 70th Annual Scientific Convention; 2015 May 14\u201316; Toronto Ontario Canada."},{"issue":"10","key":"e_1_2_9_20_1","first-page":"1","article-title":"Bedtime, rapidly absorbed sublingual cyclobenzaprine (TNX\u2010102 SL) for the treatment of fibromyalgia: results of a phase 2b randomized, double\u2010blind, placebo\u2010controlled study [abstract no. 2309]. 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