{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T18:08:03Z","timestamp":1780337283633,"version":"3.54.1"},"reference-count":29,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,3,3]],"date-time":"2025-03-03T00:00:00Z","timestamp":1740960000000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>There are several disease\u2010modifying antirheumatic drugs currently available to treat rheumatoid arthritis (RA). However, the optimal combination therapy with methotrexate for treating RA remains unclear. We aimed to identify combination therapies with high\u2010efficacy and safety by employing the Bayesian method in a network meta\u2010analysis. We systematically searched PubMed, Embase, CENTRAL, Ichushi web, and PMDA review reports and application materials through October 2020, and found 86 randomized controlled trials. The primary efficacy outcome was the 50% improvement rate according to the American College of Rheumatology criteria (ACR50), and the primary safety outcome was the incidence of serious adverse events. We calculated odds ratios (ORs) and its 95% credible intervals (CrIs) between each treatment, and the surface under the cumulative ranking curve (SUCRA) score for each treatment to rank disease\u2010modifying antirheumatic drug combinations. Individually, most disease\u2010modifying antirheumatic drugs combined with methotrexate are more likely to achieve ACR50 than methotrexate monotherapy, with significant differences (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05), whereas the incidence of serious adverse events was not significantly different compared with methotrexate monotherapy (<jats:italic>p<\/jats:italic>\u2009&gt;\u20090.05). Infliximab combined with methotrexate had the highest efficacy ranking (OR\u2009=\u200910.53, 95% CrI: [3.20, 42.87], SUCRA score: 0.884), and etanercept combined with methotrexate had the highest safety ranking (OR\u2009=\u20090.29, 95% CrI: [0.03, 2.04], SUCRA score: 0.893). Comprehensive cluster analysis revealed that the combination of etanercept, an Fc\u2010fusion protein targeting tumor necrosis factor \u03b1, with methotrexate demonstrated higher efficacy and safety. These findings could support the selection of combination therapies for the treatment of RA.<\/jats:p>","DOI":"10.1111\/cts.70156","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T06:02:29Z","timestamp":1741759349000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Comparison of the Efficacy and Safety of Disease\u2010Modifying Antirheumatic Drugs Combination Therapies: A Systematic Review and Network Meta\u2010Analysis"],"prefix":"10.1111","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-6802-2615","authenticated-orcid":false,"given":"Linfeng","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Regulatory Science, Graduate School of Pharmaceutical Sciences Nagoya City University  Nagoya Japan"},{"name":"Department of Pharmacognosy, Graduate School of Pharmaceutical Sciences Nagoya City University  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4387-9134","authenticated-orcid":false,"given":"Kaori","family":"Ambe","sequence":"additional","affiliation":[{"name":"Department of Regulatory Science, Graduate School of Pharmaceutical Sciences Nagoya City University  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayu","family":"Onishi","sequence":"additional","affiliation":[{"name":"Department of Regulatory Science, Graduate School of Pharmaceutical Sciences Nagoya City University  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuka","family":"Yoshii","sequence":"additional","affiliation":[{"name":"Department of Regulatory Science, Graduate School of Pharmaceutical Sciences Nagoya City University  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2524-8745","authenticated-orcid":false,"given":"Toshiaki","family":"Makino","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Graduate School of Pharmaceutical Sciences Nagoya City University  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2937-8926","authenticated-orcid":false,"given":"Masahiro","family":"Tohkin","sequence":"additional","affiliation":[{"name":"Department of Regulatory Science, Graduate School of Pharmaceutical Sciences Nagoya City University  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,3]]},"reference":[{"key":"e_1_2_10_2_1","unstructured":"National Institute of Arthritis and Musculoskeletal and Skin Diseases \u201cRheumatoid Arthritis \u201d2022 https:\/\/www.niams.nih.gov\/health\u2010topics\/rheumatoid\u2010arthritis."},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-017-1488-5"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2008.099861"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr.22783"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2016-210602"},{"key":"e_1_2_10_7_1","unstructured":"Japan College of Rheumatology \u201cRheumatoid Arthritis Treatment Guidelines 2020 \u201d2020 https:\/\/www.ryumachi\u2010jp.com\/publish\/guide\/."},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2014-206106"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1159\/000493390"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.2147\/JIR.S219586"},{"key":"e_1_2_10_11_1","unstructured":"H.Jpt \u201cCochrane Handbook for Systematic Reviews of Interventions Version 6.4 (Updated August 2023) \u201d2022 https:\/\/www.training.cochrane.org\/handbook."},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11606-019-05230-0"},{"key":"e_1_2_10_13_1","article-title":"No Impact of Concomitant Methotrexate Use on Serious Adverse Event and Serious Infection Risk in Patients With Rheumatoid Arthritis Treated With bDMARDs: A Systematic Literature Review and Meta\u2010Analysis","volume":"3","author":"Baradat C.","year":"2017","journal-title":"Rheumatology and Drug Monitoring Open"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/1759720X21999564"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.n71"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780380602"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.l4898"},{"key":"e_1_2_10_18_1","unstructured":"R Core Team \u201cR: A Language and Environment for Statistical Computing \u201d2022 https:\/\/www.R\u2010project.org\/."},{"key":"e_1_2_10_19_1","unstructured":"G.vanValkenhoefandJ.Kuiper \u201cgemtc: Network Meta\u2010Analysis Using Bayesian Methods \u201d2021 https:\/\/CRAN.R\u2010project.org\/package=gemtc."},{"key":"e_1_2_10_20_1","unstructured":"M.Plummer \u201crjags: Bayesian Graphical Models Using MCMC \u201d2022 https:\/\/CRAN.R\u2010project.org\/package=rjags."},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13643-017-0473-z"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/jrsm.1037"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/1467-9868.00353"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.315.7109.629"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v036.i03"},{"key":"e_1_2_10_26_1","first-page":"213","article-title":"Predictive P\u2010Score for Treatment Ranking in Bayesian Network Meta\u2010Analysis","volume":"21","author":"Rosenberger K. J.","year":"2021","journal-title":"BioMed Research International"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.i1777"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.2169\/naika.101.2880"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0305621"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr.24596"}],"container-title":["Clinical and Translational Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.70156","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,30]],"date-time":"2025-03-30T06:54:18Z","timestamp":1743317658000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1111\/cts.70156"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3]]},"references-count":29,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,3]]}},"alternative-id":["10.1111\/cts.70156"],"URL":"https:\/\/doi.org\/10.1111\/cts.70156","archive":["Portico"],"relation":{},"ISSN":["1752-8054","1752-8062"],"issn-type":[{"value":"1752-8054","type":"print"},{"value":"1752-8062","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3]]},"assertion":[{"value":"2024-11-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70156"}}