{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T21:47:42Z","timestamp":1773784062105,"version":"3.50.1"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:00:00Z","timestamp":1769040000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"},{"start":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:00:00Z","timestamp":1769040000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Rheumatol Ther"],"published-print":{"date-parts":[[2026,4]]},"DOI":"10.1007\/s40744-025-00823-0","type":"journal-article","created":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T02:41:13Z","timestamp":1769049673000},"page":"423-434","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy and Safety of Tofacitinib and Adalimumab in Rheumatoid Arthritis by Body Mass Index-Normalized Methotrexate Dose: A Post Hoc Analysis"],"prefix":"10.1007","volume":"13","clinical-trial-number":[{"clinical-trial-number":"nct02187055","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Tsutomu","family":"Takeuchi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0807-7139","authenticated-orcid":false,"given":"Yoshiya","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8453-6731","authenticated-orcid":false,"given":"Hisashi","family":"Yamanaka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kunihiro","family":"Yamaoka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5008-0665","authenticated-orcid":false,"given":"Naonobu","family":"Sugiyama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noriko","family":"Iikuni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7011-5263","authenticated-orcid":false,"given":"Shigeyuki","family":"Toyoizumi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth","family":"Kwok","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen-Chan","family":"Tsai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eduardo","family":"Mysler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert J.","family":"Moots","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josef S.","family":"Smolen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6630-1477","authenticated-orcid":false,"given":"Roy","family":"Fleischmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,1,22]]},"reference":[{"key":"823_CR1","doi-asserted-by":"publisher","first-page":"2569","DOI":"10.1002\/art.27584","volume":"62","author":"D Aletaha","year":"2010","unstructured":"Aletaha D, Neogi T, Silman AJ, et al. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology\/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010;62:2569\u201381.","journal-title":"Arthritis Rheum"},{"key":"823_CR2","doi-asserted-by":"publisher","first-page":"1094","DOI":"10.1016\/S0140-6736(10)60826-4","volume":"376","author":"DL Scott","year":"2010","unstructured":"Scott DL, Wolfe F, Huizinga TW. Rheumatoid arthritis. Lancet. 2010;376:1094\u2013108.","journal-title":"Lancet"},{"key":"823_CR3","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1186\/1477-7525-7-25","volume":"7","author":"F Salaffi","year":"2009","unstructured":"Salaffi F, Carotti M, Gasparini S, Intorcia M, Grassi W. The health-related quality of life in rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis: a comparison with a selected sample of healthy people. Health Qual Life Outcomes. 2009;7:25.","journal-title":"Health Qual Life Outcomes"},{"key":"823_CR4","doi-asserted-by":"publisher","first-page":"1108","DOI":"10.1002\/art.41752","volume":"73","author":"L Fraenkel","year":"2021","unstructured":"Fraenkel L, Bathon JM, England BR, et al. 2021 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Rheumatol. 2021;73:1108\u201323.","journal-title":"Arthritis Rheumatol"},{"key":"823_CR5","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1093\/mr\/roac017","volume":"33","author":"Y Kawahito","year":"2022","unstructured":"Kawahito Y, Morinobu A, Kaneko Y, et al. Drug treatment algorithm and recommendations from the 2020 update of the Japan College of Rheumatology clinical practice guidelines for the management of rheumatoid arthritis-secondary publication. Mod Rheumatol. 2022;33:21\u201335.","journal-title":"Mod Rheumatol"},{"key":"823_CR6","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1136\/ard-2022-223356","volume":"82","author":"JS Smolen","year":"2023","unstructured":"Smolen JS, Landew\u00e9 RBM, Bergstra SA, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update. Ann Rheum Dis. 2023;82:3\u201318.","journal-title":"Ann Rheum Dis"},{"key":"823_CR7","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1016\/S0140-6736(12)61424-X","volume":"381","author":"GR Burmester","year":"2013","unstructured":"Burmester GR, Blanco R, Charles-Schoeman C, et al. Tofacitinib (CP-690,550) in combination with methotrexate in patients with active rheumatoid arthritis with an inadequate response to tumour necrosis factor inhibitors: a randomised phase 3 trial. Lancet. 2013;381:451\u201360.","journal-title":"Lancet"},{"key":"823_CR8","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1056\/NEJMoa1109071","volume":"367","author":"R Fleischmann","year":"2012","unstructured":"Fleischmann R, Kremer J, Cush J, et al. Placebo-controlled trial of tofacitinib monotherapy in rheumatoid arthritis. N Engl J Med. 2012;367:495\u2013507.","journal-title":"N Engl J Med"},{"key":"823_CR9","doi-asserted-by":"publisher","first-page":"2377","DOI":"10.1056\/NEJMoa1310476","volume":"370","author":"EB Lee","year":"2014","unstructured":"Lee EB, Fleischmann R, Hall S, et al. Tofacitinib versus methotrexate in rheumatoid arthritis. N Engl J Med. 2014;370:2377\u201386.","journal-title":"N Engl J Med"},{"key":"823_CR10","doi-asserted-by":"publisher","first-page":"253","DOI":"10.7326\/0003-4819-159-4-201308200-00006","volume":"159","author":"J Kremer","year":"2013","unstructured":"Kremer J, Li Z-G, Hall S, et al. Tofacitinib in combination with nonbiologic disease-modifying antirheumatic drugs in patients with active rheumatoid arthritis: a randomized trial. Ann Intern Med. 2013;159:253\u201361.","journal-title":"Ann Intern Med"},{"key":"823_CR11","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1002\/art.37816","volume":"65","author":"D van der Heijde","year":"2013","unstructured":"van der Heijde D, Tanaka Y, Fleischmann R, et al. Tofacitinib (CP-690,550) in patients with rheumatoid arthritis receiving methotrexate: twelve-month data from a twenty-four-month phase III randomized radiographic study. Arthritis Rheum. 2013;65:559\u201370.","journal-title":"Arthritis Rheum"},{"key":"823_CR12","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1056\/NEJMoa1112072","volume":"367","author":"RF van Vollenhoven","year":"2012","unstructured":"van Vollenhoven RF, Fleischmann R, Cohen S, et al. Tofacitinib or adalimumab versus placebo in rheumatoid arthritis. N Engl J Med. 2012;367:508\u201319.","journal-title":"N Engl J Med"},{"key":"823_CR13","doi-asserted-by":"publisher","first-page":"878","DOI":"10.1002\/art.40803","volume":"71","author":"D van der Heijde","year":"2019","unstructured":"van der Heijde D, Strand V, Tanaka Y, et al. Tofacitinib in combination with methotrexate in patients with rheumatoid arthritis: clinical efficacy, radiographic, and safety outcomes from a twenty-four-month, phase III study. Arthritis Rheumatol. 2019;71:878\u201391.","journal-title":"Arthritis Rheumatol"},{"key":"823_CR14","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1016\/S0140-6736(17)31618-5","volume":"390","author":"R Fleischmann","year":"2017","unstructured":"Fleischmann R, Mysler E, Hall S, et al. Efficacy and safety of tofacitinib monotherapy, tofacitinib with methotrexate, and adalimumab with methotrexate in patients with rheumatoid arthritis (ORAL Strategy): a phase 3b\/4, double-blind, head-to-head, randomised controlled trial. Lancet. 2017;390:457\u201368.","journal-title":"Lancet"},{"key":"823_CR15","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1056\/NEJMoa2109927","volume":"386","author":"SR Ytterberg","year":"2022","unstructured":"Ytterberg SR, Bhatt DL, Mikuls TR, et al. Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis. N Engl J Med. 2022;386:316\u201326.","journal-title":"N Engl J Med"},{"key":"823_CR16","doi-asserted-by":"publisher","first-page":"1037","DOI":"10.1136\/annrheumdis-2013-204769","volume":"74","author":"GR Burmester","year":"2015","unstructured":"Burmester GR, Kivitz AJ, Kupper H, et al. Efficacy and safety of ascending methotrexate dose in combination with adalimumab: the randomised CONCERTO trial. Ann Rheum Dis. 2015;74:1037\u201344.","journal-title":"Ann Rheum Dis"},{"key":"823_CR17","doi-asserted-by":"publisher","first-page":"1086","DOI":"10.1136\/ard.2008.094474","volume":"68","author":"K Visser","year":"2009","unstructured":"Visser K, Katchamart W, Loza E, et al. Multinational evidence-based recommendations for the use of methotrexate in rheumatic disorders with a focus on rheumatoid arthritis: integrating systematic literature research and expert opinion of a broad international panel of rheumatologists in the 3E Initiative. Ann Rheum Dis. 2009;68:1086\u201393.","journal-title":"Ann Rheum Dis"},{"key":"823_CR18","first-page":"313","volume":"16","author":"DE Furst","year":"1989","unstructured":"Furst DE, Koehnke R, Burmeister LF, Kohler J, Cargill I. Increasing methotrexate effect with increasing dose in the treatment of resistant rheumatoid arthritis. J Rheumatol. 1989;16:313\u201320.","journal-title":"J Rheumatol"},{"key":"823_CR19","doi-asserted-by":"publisher","first-page":"98","DOI":"10.3109\/s10165-006-0546-7","volume":"17","author":"H Yamanaka","year":"2007","unstructured":"Yamanaka H, Inoue E, Tanaka E, et al. Influence of methotrexate dose on its efficacy and safety in rheumatoid arthritis patients: evidence based on the variety of prescribing approaches among practicing Japanese rheumatologists in a single institute-based large observational cohort (IORRA). Mod Rheumatol. 2007;17:98\u2013105.","journal-title":"Mod Rheumatol"},{"key":"823_CR20","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1136\/annrheumdis-2012-202433","volume":"73","author":"T Takeuchi","year":"2014","unstructured":"Takeuchi T, Yamanaka H, Ishiguro N, et al. Adalimumab, a human anti-TNF monoclonal antibody, outcome study for the prevention of joint damage in Japanese patients with early rheumatoid arthritis: the HOPEFUL 1 study. Ann Rheum Dis. 2014;73:536\u201343.","journal-title":"Ann Rheum Dis"},{"key":"823_CR21","volume":"2013","author":"B Shea","year":"2013","unstructured":"Shea B, Swinden MV, Tanjong Ghogomu E, et al. Folic acid and folinic acid for reducing side effects in patients receiving methotrexate for rheumatoid arthritis. Cochrane Database Syst Rev. 2013;2013:CD000951.","journal-title":"Cochrane Database Syst Rev"},{"key":"823_CR22","doi-asserted-by":"publisher","first-page":"1552","DOI":"10.1002\/1529-0131(199809)41:9<1552::AID-ART5>3.0.CO;2-W","volume":"41","author":"RN Maini","year":"1998","unstructured":"Maini RN, Breedveld FC, Kalden JR, et al. Therapeutic efficacy of multiple intravenous infusions of anti-tumor necrosis factor alpha monoclonal antibody combined with low-dose weekly methotrexate in rheumatoid arthritis. Arthritis Rheum. 1998;41:1552\u201363.","journal-title":"Arthritis Rheum"},{"key":"823_CR23","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1007\/s10067-016-3436-1","volume":"36","author":"R Fleischmann","year":"2017","unstructured":"Fleischmann R, Mease PJ, Schwartzman S, et al. Efficacy of tofacitinib in patients with rheumatoid arthritis stratified by background methotrexate dose group. Clin Rheumatol. 2017;36:15\u201324.","journal-title":"Clin Rheumatol"},{"key":"823_CR24","doi-asserted-by":"publisher","DOI":"10.1136\/rmdopen-2016-000363","volume":"3","author":"C Takahashi","year":"2017","unstructured":"Takahashi C, Kaneko Y, Okano Y, et al. Association of erythrocyte methotrexate-polyglutamate levels with the efficacy and hepatotoxicity of methotrexate in patients with rheumatoid arthritis: a 76-week prospective study. RMD Open. 2017;3:e000363.","journal-title":"RMD Open"},{"key":"823_CR25","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1080\/14397595.2018.1472358","volume":"29","author":"H Kameda","year":"2019","unstructured":"Kameda H, Fujii T, Nakajima A, et al. Japan College of Rheumatology guideline for the use of methotrexate in patients with rheumatoid arthritis. Mod Rheumatol. 2019;29:31\u201340.","journal-title":"Mod Rheumatol"},{"key":"823_CR26","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1080\/14397595.2018.1553489","volume":"29","author":"T Takeuchi","year":"2019","unstructured":"Takeuchi T, Yamanaka H, Yamaoka K, et al. Efficacy and safety of tofacitinib in Japanese patients with rheumatoid arthritis by background methotrexate dose: a post hoc analysis of clinical trial data. Mod Rheumatol. 2019;29:756\u201366.","journal-title":"Mod Rheumatol"},{"key":"823_CR27","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2014-207005","volume":"74","author":"SHM Manders","year":"2015","unstructured":"Manders SHM, Kievit W, Adang E, et al. Effectiveness of TNF inhibitor treatment with various methotrexate doses in patients with rheumatoid arthritis: results from clinical practice. Ann Rheum Dis. 2015;74:e24.","journal-title":"Ann Rheum Dis"},{"key":"823_CR28","doi-asserted-by":"publisher","DOI":"10.1136\/rmdopen-2021-002103","volume":"8","author":"AH Dikranian","year":"2022","unstructured":"Dikranian AH, Gonzalez-Gay MA, Wellborne F, et al. Efficacy of tofacitinib in patients with rheumatoid arthritis stratified by baseline body mass index: an analysis of pooled data from phase 3 studies. RMD Open. 2022;8:e002103.","journal-title":"RMD Open"}],"container-title":["Rheumatology and Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40744-025-00823-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s40744-025-00823-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40744-025-00823-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T18:06:02Z","timestamp":1773770762000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s40744-025-00823-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,22]]},"references-count":28,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["823"],"URL":"https:\/\/doi.org\/10.1007\/s40744-025-00823-0","relation":{},"ISSN":["2198-6576","2198-6584"],"issn-type":[{"value":"2198-6576","type":"print"},{"value":"2198-6584","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,22]]},"assertion":[{"value":"6 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 December 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 January 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Tsutomu Takeuchi has received research grants and consultancy fees from AbbVie, Asahi Kasei, Astellas, AstraZeneca, AYUMI, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Eli Lilly Japan, Janssen, Mitsubishi Tanabe, Nippon Kayaku, Novartis, Pfizer Japan Inc, Taiho, Taisho Toyama, Takeda, and Teijin. Yoshiya Tanaka has received research grants from Chugai, Eisai, Mitsubishi Tanabe, and Taisho, and speaker fees and\/or honoraria from AbbVie, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, Eisai, Eli Lilly, Gilead, GlaxoSmithKline, Pfizer Inc, Taiho, and Taisho. Hisashi Yamanaka has received speaker or consultancy fees from AbbVie, Chugai, Teijin Pharma, and YLBio. Kunihiro Yamaoka has received speaker and consultancy fees from Actelion, Astellas, Chugai, Eisai, Eli Lilly, GlaxoSmithKline, Janssen, Mitsubishi Tanabe, Nippon Shinyaku, Pfizer Inc, and Takeda. Naonobu Sugiyama was an employee and shareholder of Pfizer Japan Inc at the time of the study\/analysis and is a current employee of Bristol Myers Squibb K.K. Noriko Iikuni was an employee of Pfizer Inc at the time of the study\/analysis, and is a current employee of Xencor Inc. Shigeyuki Toyoizumi is an employee of Pfizer R&D Japan. Kenneth Kwok is an employee and shareholder of Pfizer Inc. Wen-Chan Tsai has received speaker and consultancy fees from Abbott, AstraZeneca, Bristol Myers Squibb, Chugai, Janssen, Mitsubishi Tanabe, Pfizer Inc, and Roche. Eduardo Mysler has received research grants and consultancy fees from AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen, Pfizer Inc, Roche, and Sanofi. Robert J. Moots has received research grants and speaker and consultancy fees from AbbVie, Bristol Myers Squibb, Chugai, Eli Lilly, Novartis, Pfizer Inc, Roche, Sandoz, and UCB. Josef S. Smolen has received research grants from AbbVie, Eli Lilly, Janssen, MSD, Pfizer Inc, and Roche, and consultancy fees from AbbVie, Amgen, AstraZeneca, Astro, Celgene, Celltrion, Eli Lilly, GlaxoSmithKline, ILTOO, Janssen, Medimmune, MSD, Novartis-Sandoz, Pfizer Inc, Roche, Samsung, Sanofi, and UCB. Roy Fleischmann has received consultancy fees from AbbVie, Almirall, Artiva Biotherapeutics, Atomwise, Biohaven Pharmaceuticals, Bristol Myers Squibb, Cyoxone, Deep Cure, Dren Bio, ECOR, Galvani, Gates Bio, Gilead, GlaxoSmithKline, Halia, Immunovant, ImmuneMed, InventisBio, Istesso, Janssen, Janux, Eli Lilly, Monte Rosa, MSD, Novartis, Overland, Pfizer Inc, Synact, TPG, UCB, VYNE Therapeutics, and Xencor. Roy Fleischmann is the Editor-in-Chief of\n                      Rheumatology and Therapy\n                      . Roy Fleischmann was not involved in the selection of peer reviewers for the manuscript nor any of the subsequent editorial decisions.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}},{"value":"All procedures were conducted in accordance with the Declaration of Helsinki and International Council for Harmonisation Guidelines for Good Clinical Practice, and were approved by the Institutional Review Board\/Ethics Committee at each study center. All patients provided written informed consent.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Approval"}}]}}