{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T11:26:46Z","timestamp":1793618806777,"version":"4.5.0"},"reference-count":20,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2023,11,9]],"date-time":"2023-11-09T00:00:00Z","timestamp":1699488000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Preliminary evidence suggests that vagus nerve stimulation (VNS) may have some benefit in patients with rheumatoid arthritis (RA); however, prior studies have been small and\/or uncontrolled; this study aimed to address that gap.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This randomized, double\u2010blind, sham\u2010controlled trial enrolled patients aged 18 to 75\u2009years with active RA who had failed conventional synthetic disease\u2010modifying antirheumatic drugs (DMARDs) and were na\u00efve to biologic and\/or targeted synthetic DMARDs. All patients received an auricular vagus nerve stimulator and were randomized 1:1 to active stimulation or sham. The primary endpoint was the proportion of patients achieving 20% improvement in American College of Rheumatology criteria (ACR20) at week 12. Secondary endpoints included mean changes in disease activity score of 28 joints with C\u2010reactive protein (DAS28\u2010CRP) and Health Assessment Questionnaire\u2010Disability Index (HAQ\u2010DI).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 113 patients (mean age 54\u2009years; 82% female) enrolled, and 101 patients (89.4%) completed week 12. ACR20 response at week 12 was 25.0% for active stimulation versus 26.9% for sham (difference vs. sham, \u22121.9; 95% CI, \u221218.8, 14.9, <jats:italic>P<\/jats:italic> =\u20090.823). The least square mean \u00b1 SE change in DAS28\u2010CRP was \u22120.95 \u00b1\u20090.16 for active stimulation and \u22120.66 \u00b1\u20090.16 for sham (<jats:italic>P<\/jats:italic> =\u20090.201); in HAQ\u2010DI it was \u22120.19 \u00b1\u20090.06 for active stimulation and \u22120.02 \u00b1\u20090.06 for sham (<jats:italic>P<\/jats:italic> =\u20090.044). Adverse events occurred in 17 patients (15%); all were mild or moderate.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Auricular VNS did not meaningfully improve RA disease activity. If VNS with other modalities is pursued in the future for the treatment of RA, larger, controlled studies will be needed to understand its utility.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.42637","type":"journal-article","created":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T15:38:07Z","timestamp":1688139487000},"page":"2107-2115","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["A Randomized, <scp>Double\u2010Blind<\/scp>, <scp>Sham\u2010Controlled<\/scp>, Clinical Trial of Auricular Vagus Nerve Stimulation for the Treatment of Active Rheumatoid Arthritis"],"prefix":"10.1002","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0002-1907","authenticated-orcid":false,"given":"Matthew C.","family":"Baker","sequence":"first","affiliation":[{"name":"Stanford University  Stanford California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Kavanagh","sequence":"additional","affiliation":[{"name":"Kavanagh Statistical Consulting LLC  Apex North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9226-979X","authenticated-orcid":false,"given":"Stanley","family":"Cohen","sequence":"additional","affiliation":[{"name":"Metroplex Clinical Research Center  Dallas Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan K.","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Arthritis and Rheumatism Associates PC  Wheaton Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ara","family":"Dikranian","sequence":"additional","affiliation":[{"name":"Cabrillo Center for Rheumatic Disease  San Diego California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Tesser","sequence":"additional","affiliation":[{"name":"Arizona Arthritis &amp; Rheumatology Associates  Phoenix"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Kivitz","sequence":"additional","affiliation":[{"name":"Altoona Center for Clinical Research  Duncansville Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos","family":"Alataris","sequence":"additional","affiliation":[{"name":"N\u0113sos  Redwood City California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5294-4503","authenticated-orcid":false,"given":"Mark C.","family":"Genovese","sequence":"additional","affiliation":[{"name":"Stanford University, Stanford, California, and Gilead Sciences Inc  Foster City California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,11,9]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1004965"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra2103726"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2018.1"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2011.145"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2109927"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1605635113"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2566"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01321"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-020711-075015"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1566-0702(00)00215-0"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ca.1089"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2665-9913(20)30425-2"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2665-9913(20)30172-7"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.27584"},{"key":"e_1_2_8_16_1","volume":"38","author":"Felson DT, Anderson JJ, Boers M","journal-title":"Arthritis Rheum"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0258(19960715)15:13<1421::AID-SIM266>3.0.CO;2-H"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cct.2003.10.016"},{"key":"e_1_2_8_19_1","first-page":"700","article-title":"Interpreting estimates of treatment effects: implications for managed care","volume":"33","author":"Faraone SV","year":"2008","journal-title":"P T"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brs.2014.11.018"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20120571"}],"container-title":["Arthritis &amp; 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