{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T08:00:19Z","timestamp":1790150419616,"version":"4.0.1"},"reference-count":46,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J of Rheum Dis"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Knee osteoarthritis causes major pain and disability, yet disease\u2010modifying drugs remain limited. Tofacitinib, an oral Janus kinase (JAK) inhibitor, suppresses pro\u2010inflammatory cytokine signaling implicated in osteoarthritis but is unexplored in the knee; we evaluated it versus placebo in early\u2010grade disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this single\u2010center, randomized, double\u2010blind, placebo\u2010controlled trial, 100 patients with Kellgren\u2013Lawrence Grades 1 and 2 knee osteoarthritis were randomized to tofacitinib 11\u2009mg extended\u2010release once daily (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200949) or placebo (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200951) for 12\u2009weeks. The primary outcome was change in VAS pain to Week 12; secondary outcomes were WOMAC, Oxford Knee Score, EQ\u20105D\u20105L, and analgesic use, assessed to Week 12 and a Month\u20106 follow\u2010up, and analyzed by intention\u2010to\u2010treat with a mixed model for repeated measures.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Baseline characteristics were balanced. Both groups improved within\u2010group during treatment (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), but between\u2010group differences were not significant; the Week\u201012 VAS effect (tofacitinib minus placebo) was +0.02 (95% CI \u22120.84 to 0.89), with WOMAC, Oxford Knee Score, and EQ\u20105D\u20105L likewise excluding their minimal clinically important differences. Improvements rebounded toward baseline by Month 6. Drug\u2010related adverse events were more frequent with tofacitinib (14.3% vs. 0%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.005) but were gastrointestinal and self\u2010limiting.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Tofacitinib was not superior to placebo in early\u2010grade knee osteoarthritis, and the large within\u2010group improvement rebounded toward baseline by 6\u2009months, consistent with a predominantly non\u2010specific (contextual) response. Because participants were selected radiographically without inflammatory phenotyping, these findings do not support tofacitinib in unselected early\u2010grade disease but cannot exclude benefit in an inflammatory phenotype; future trials should stratify accordingly, with longer follow\u2010up and structural outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>Clinical Trials Registry of India: CTRI\/2025\/07\/090567<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/1756-185x.70877","type":"journal-article","created":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T03:54:27Z","timestamp":1789790067000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy and Safety of Tofacitinib Versus Placebo in Patients With Early\u2010Grade Knee Osteoarthritis: A Randomized, Double\u2010Blind, Placebo\u2010Controlled Trial"],"prefix":"10.1111","volume":"29","author":[{"given":"Rini","family":"Fasni","sequence":"first","affiliation":[{"name":"Department of Pharmacology All India Institute of Medical Sciences (AIIMS)  Bhubaneswar Odisha India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sujit Kumar","family":"Tripathy","sequence":"additional","affiliation":[{"name":"Department of Orthopedics All India Institute of Medical Sciences (AIIMS)  Bhubaneswar Odisha India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8837-299X","authenticated-orcid":false,"given":"Archana","family":"Mishra","sequence":"additional","affiliation":[{"name":"Department of Pharmacology All India Institute of Medical Sciences (AIIMS)  Bhubaneswar Odisha India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2772-7707","authenticated-orcid":false,"given":"Shahnawaz","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Orthopedics All India Institute of Medical Sciences (AIIMS)  Bhubaneswar Odisha India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachita","family":"Meher","sequence":"additional","affiliation":[{"name":"Department of Pharmacology All India Institute of Medical Sciences (AIIMS)  Bhubaneswar Odisha India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jagat","family":"Panda","sequence":"additional","affiliation":[{"name":"Department of Orthopedics All India Institute of Medical Sciences (AIIMS)  Bhubaneswar Odisha India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7339-1773","authenticated-orcid":false,"given":"Debasish","family":"Hota","sequence":"additional","affiliation":[{"name":"Department of Pharmacology All India Institute of Medical Sciences (AIIMS)  Bhubaneswar Odisha India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0663-0922","authenticated-orcid":false,"given":"Anand","family":"Srinivasan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology All India Institute of Medical Sciences (AIIMS)  Bhubaneswar Odisha India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,18]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(19)30417\u20109"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis\u20102019\u2010216515"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.4103\/0019\u20105413.189608"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2012.11.012"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2016.136"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2012.02.012"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2010.159"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2010.01.013"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2019.06.011"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr.24131"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(17)31744\u20100"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2017.5283"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis\u20102012\u2010202576"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2017.201"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1112072"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1109071"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1606910"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2013.44"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780290816"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.16.4.494"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr.20543"},{"issue":"12","key":"e_1_2_13_23_1","first-page":"1833","article-title":"Validation Study of WOMAC: A Health Status Instrument for Measuring Clinically Important Patient\u2010Relevant Outcomes to Antirheumatic Drug Therapy in Patients With Osteoarthritis of the Hip or Knee","volume":"15","author":"Bellamy N.","year":"1988","journal-title":"Journal of Rheumatology"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1302\/0301\u2010620X.80B1.7859"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11136\u2010011\u20109903\u2010x"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jval.2021.11.1370"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0000000000000353"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2020.01.007"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.pmbts.2017.03.003"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2021.07.003"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10753\u2010023\u201001840\u20103"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202410795"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2018.08.002"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2008.092015"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis\u20102015\u2010208387"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.30471"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.191291"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.21258"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10195\u2010017\u20100473\u20108"},{"issue":"1","key":"e_1_2_13_40_1","first-page":"126","article-title":"Correlation of Anxiety and Chronic Pain to Grade of Synovitis in Patients With Knee Osteoarthritis","volume":"31","author":"Ostojic M.","year":"2019","journal-title":"Psychiatria Danubina"},{"key":"e_1_2_13_41_1","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0000000000000467"},{"key":"e_1_2_13_42_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2004.022905"},{"key":"e_1_2_13_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr.22538"},{"key":"e_1_2_13_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2004.02.001"},{"key":"e_1_2_13_45_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2109927"},{"key":"e_1_2_13_46_1","volume-title":"FDA Requires Warnings About Increased Risk of Serious Heart\u2010Related Events, Cancer, Blood Clots, and Death for JAK Inhibitors That Treat Certain Chronic Inflammatory Conditions","author":"US Food and Drug Administration","year":"2021"},{"key":"e_1_2_13_47_1","volume-title":"Janus Kinase Inhibitors (JAKi)\u2014Referral","author":"European Medicines Agency","year":"2023"}],"container-title":["International Journal of Rheumatic Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1756-185x.70877","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/1756-185x.70877","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1756-185x.70877","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T07:05:52Z","timestamp":1790147152000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/1756-185x.70877"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":46,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1111\/1756-185x.70877"],"URL":"https:\/\/doi.org\/10.1111\/1756-185x.70877","archive":["Portico"],"relation":{},"ISSN":["1756-1841","1756-185X"],"issn-type":[{"value":"1756-1841","type":"print"},{"value":"1756-185X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9]]},"assertion":[{"value":"2026-07-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70877"}}