{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T22:10:14Z","timestamp":1794003014282,"version":"4.8.0"},"reference-count":49,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T00:00:00Z","timestamp":1733011200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T00:00:00Z","timestamp":1733011200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2024,10,31]],"date-time":"2024-10-31T00:00:00Z","timestamp":1730332800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["clinicalkey.fr","clinicalkey.jp","clinicalkey.es","clinicalkey.com.au","clinicalkey.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Autoimmunity"],"published-print":{"date-parts":[[2024,12]]},"DOI":"10.1016\/j.jaut.2024.103331","type":"journal-article","created":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T10:34:43Z","timestamp":1730889283000},"page":"103331","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":27,"special_numbering":"C","title":["Efficacy and safety of Advanced Combination Treatment in immune-mediated inflammatory disease: A systematic review and meta-analysis of randomized controlled trials"],"prefix":"10.1016","volume":"149","author":[{"given":"Virginia","family":"Solitano","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhong","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siddharth","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga Maria","family":"Nardone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gionata","family":"Fiorino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Laura","family":"Acosta Felquer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lillian","family":"Barra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria-Antonietta","family":"D'Agostino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet","family":"Pope","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Peyrin-Biroulet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvio","family":"Danese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vipul","family":"Jairath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"5","key":"10.1016\/j.jaut.2024.103331_bib1","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1053\/j.gastro.2021.09.078","article-title":"Breaking through the therapeutic ceiling: what will it take?","volume":"162","author":"Raine","year":"2022","journal-title":"Gastroenterology"},{"issue":"1","key":"10.1016\/j.jaut.2024.103331_bib2","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1053\/j.gastro.2006.11.041","article-title":"Adalimumab for maintenance of clinical response and remission in patients with Crohn's disease: the CHARM trial","volume":"132","author":"Colombel","year":"2007","journal-title":"Gastroenterology"},{"issue":"9317","key":"10.1016\/j.jaut.2024.103331_bib3","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1016\/S0140-6736(02)08512-4","article-title":"Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial","volume":"359","author":"Hanauer","year":"2002","journal-title":"Lancet"},{"issue":"2","key":"10.1016\/j.jaut.2024.103331_bib4","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1111\/apt.13243","article-title":"Population pharmacokinetics-pharmacodynamics of vedolizumab in patients with ulcerative colitis and Crohn's disease","volume":"42","author":"Rosario","year":"2015","journal-title":"Aliment. Pharmacol. Ther."},{"issue":"7","key":"10.1016\/j.jaut.2024.103331_bib5","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/S2468-1253(21)00065-0","article-title":"Breaking the therapeutic ceiling in drug development in ulcerative colitis","volume":"6","author":"Alsoud","year":"2021","journal-title":"Lancet Gastroenterol Hepatol"},{"issue":"10","key":"10.1016\/j.jaut.2024.103331_bib6","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1038\/s41577-021-00603-1","article-title":"Immune-mediated inflammatory disease therapeutics: past, present and future","volume":"21","author":"McInnes","year":"2021","journal-title":"Nat. Rev. Immunol."},{"issue":"7","key":"10.1016\/j.jaut.2024.103331_bib7","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1056\/NEJMra1909094","article-title":"Reframing immune-mediated inflammatory diseases through signature cytokine hubs","volume":"385","author":"Schett","year":"2021","journal-title":"N. Engl. J. Med."},{"issue":"12","key":"10.1016\/j.jaut.2024.103331_bib8","doi-asserted-by":"crossref","first-page":"2380","DOI":"10.1136\/gutjnl-2022-327025","article-title":"The future of drug development for inflammatory bowel disease: the need to ACT (advanced combination treatment)","volume":"71","author":"Danese","year":"2022","journal-title":"Gut"},{"issue":"5","key":"10.1016\/j.jaut.2024.103331_bib9","first-page":"251","article-title":"Advanced combination treatment with biologic agents and novel small molecule drugs for inflammatory bowel disease","volume":"19","author":"Solitano","year":"2023","journal-title":"Gastroenterol. Hepatol."},{"issue":"5","key":"10.1016\/j.jaut.2024.103331_bib10","doi-asserted-by":"crossref","DOI":"10.1016\/j.jbspin.2023.105578","article-title":"Rationale, current state and opportunities in combining biologic disease modifying antirheumatic drugs in rheumatoid and psoriatic arthritis","volume":"90","author":"Mutlu","year":"2023","journal-title":"Joint Bone Spine"},{"issue":"9","key":"10.1016\/j.jaut.2024.103331_bib11","doi-asserted-by":"crossref","first-page":"637","DOI":"10.7326\/M16-2575","article-title":"Oral direct-acting agent therapy for hepatitis C virus infection: a systematic review","volume":"166","author":"Falade-Nwulia","year":"2017","journal-title":"Ann. Intern. Med."},{"issue":"7","key":"10.1016\/j.jaut.2024.103331_bib12","doi-asserted-by":"crossref","first-page":"468","DOI":"10.7326\/M13-2526","article-title":"Effectiveness of combination therapy with statin and another lipid-modifying agent compared with intensified statin monotherapy: a systematic review","volume":"160","author":"Gudzune","year":"2014","journal-title":"Ann. Intern. Med."},{"issue":"8","key":"10.1016\/j.jaut.2024.103331_bib13","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1001\/jamaneurol.2014.808","article-title":"Effectiveness of antiepileptic drug combination therapy for partial-onset seizures based on mechanisms of action","volume":"71","author":"Margolis","year":"2014","journal-title":"JAMA Neurol."},{"issue":"9","key":"10.1016\/j.jaut.2024.103331_bib14","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1016\/j.cgh.2018.02.024","article-title":"Combining biologics in inflammatory bowel disease and other immune mediated inflammatory disorders","volume":"16","author":"Hirten","year":"2018","journal-title":"Clin. Gastroenterol. Hepatol."},{"issue":"3","key":"10.1016\/j.jaut.2024.103331_bib15","doi-asserted-by":"crossref","first-page":"e361","DOI":"10.1016\/j.cgh.2021.03.034","article-title":"Dual biologic or small molecule therapy for treatment of inflammatory bowel disease: a systematic review and meta-analysis","volume":"20","author":"Ahmed","year":"2022","journal-title":"Clin. Gastroenterol. Hepatol."},{"issue":"1","key":"10.1016\/j.jaut.2024.103331_bib16","article-title":"Systematic review with meta-analysis: safety and effectiveness of combining biologics and small molecules in inflammatory bowel disease","volume":"4","author":"Alayo","year":"2022","journal-title":"Crohns Colitis"},{"issue":"1","key":"10.1016\/j.jaut.2024.103331_bib17","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.semarthrit.2018.12.003","article-title":"Safety of combination therapy with two bDMARDs in patients with rheumatoid arthritis: a systematic review and meta-analysis","volume":"49","author":"Boleto","year":"2019","journal-title":"Semin. Arthritis Rheum."},{"issue":"7650","key":"10.1016\/j.jaut.2024.103331_bib18","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1136\/bmj.39489.470347.AD","article-title":"GRADE: an emerging consensus on rating quality of evidence and strength of recommendations","volume":"336","author":"Guyatt","year":"2008","journal-title":"BMJ"},{"key":"10.1016\/j.jaut.2024.103331_bib19","article-title":"The PRISMA 2020 statement: an updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"10.1016\/j.jaut.2024.103331_bib20","article-title":"RoB 2: a revised tool for assessing risk of bias in randomised trials","volume":"366","author":"Sterne","year":"2019","journal-title":"BMJ"},{"issue":"3","key":"10.1016\/j.jaut.2024.103331_bib21","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/0197-2456(86)90046-2","article-title":"Meta-analysis in clinical trials","volume":"7","author":"DerSimonian","year":"1986","journal-title":"Contr. Clin. Trials"},{"issue":"7414","key":"10.1016\/j.jaut.2024.103331_bib22","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1136\/bmj.327.7414.557","article-title":"Measuring inconsistency in meta-analyses","volume":"327","author":"Higgins","year":"2003","journal-title":"BMJ"},{"issue":"7304","key":"10.1016\/j.jaut.2024.103331_bib23","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1136\/bmj.323.7304.101","article-title":"Systematic reviews in health care: investigating and dealing with publication and other biases in meta-analysis","volume":"323","author":"Sterne","year":"2001","journal-title":"BMJ"},{"issue":"4","key":"10.1016\/j.jaut.2024.103331_bib24","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.jclinepi.2010.07.015","article-title":"GRADE guidelines: 3. Rating the quality of evidence","volume":"64","author":"Balshem","year":"2011","journal-title":"J. Clin. Epidemiol."},{"issue":"10","key":"10.1016\/j.jaut.2024.103331_bib25","doi-asserted-by":"crossref","first-page":"2633","DOI":"10.1007\/s10067-018-4164-5","article-title":"Niclosamide as an adjuvant to etanercept in treatment patients with active rheumatoid arthritis: an 8-week randomized controlled pilot study","volume":"37","author":"Al-Gareeb","year":"2018","journal-title":"Clin. Rheumatol."},{"issue":"5","key":"10.1016\/j.jaut.2024.103331_bib26","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1002\/art.20221","article-title":"Combination therapy with etanercept and anakinra in the treatment of patients with rheumatoid arthritis who have been treated unsuccessfully with methotrexate","volume":"50","author":"Genovese","year":"2004","journal-title":"Arthritis Rheum."},{"issue":"8","key":"10.1016\/j.jaut.2024.103331_bib27","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1136\/annrheumdis-2018-214943","article-title":"Efficacy and safety of bimekizumab as add-on therapy for rheumatoid arthritis in patients with inadequate response to certolizumab pegol: a proof-of-concept study","volume":"78","author":"Glatt","year":"2019","journal-title":"Ann. Rheum. Dis."},{"issue":"3","key":"10.1016\/j.jaut.2024.103331_bib28","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1002\/art.30194","article-title":"Evaluation of the safety of rituximab in combination with a tumor necrosis factor inhibitor and methotrexate in patients with active rheumatoid arthritis: results from a randomized controlled trial","volume":"63","author":"Greenwald","year":"2011","journal-title":"Arthritis Rheum."},{"issue":"2","key":"10.1016\/j.jaut.2024.103331_bib29","first-page":"470","article-title":"Efficacy and safety of combined etanercept and iguratimod for active rheumatoid arthritis","volume":"27","author":"Yulan Sun","year":"2016","journal-title":"Biomed. Res."},{"issue":"9","key":"10.1016\/j.jaut.2024.103331_bib30","doi-asserted-by":"crossref","first-page":"2807","DOI":"10.1002\/art.22070","article-title":"Safety of the selective costimulation modulator abatacept in rheumatoid arthritis patients receiving background biologic and nonbiologic disease-modifying antirheumatic drugs: a one-year randomized, placebo-controlled study","volume":"54","author":"Weinblatt","year":"2006","journal-title":"Arthritis Rheum."},{"issue":"2","key":"10.1016\/j.jaut.2024.103331_bib31","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1136\/ard.2006.055111","article-title":"Selective costimulation modulation using abatacept in patients with active rheumatoid arthritis while receiving etanercept: a randomised clinical trial","volume":"66","author":"Weinblatt","year":"2007","journal-title":"Ann. Rheum. Dis."},{"issue":"1","key":"10.1016\/j.jaut.2024.103331_bib32","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1002\/art.41466","article-title":"Phase II randomized trial of rituximab plus cyclophosphamide followed by belimumab for the treatment of lupus nephritis","volume":"73","author":"Atisha-Fregoso","year":"2021","journal-title":"Arthritis Rheumatol."},{"issue":"4","key":"10.1016\/j.jaut.2024.103331_bib33","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/S2468-1253(22)00427-7","article-title":"Guselkumab plus golimumab combination therapy versus guselkumab or golimumab monotherapy in patients with ulcerative colitis (VEGA): a randomised, double-blind, controlled, phase 2, proof-of-concept trial","volume":"8","author":"Feagan","year":"2023","journal-title":"Lancet Gastroenterol Hepatol"},{"issue":"1","key":"10.1016\/j.jaut.2024.103331_bib34","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1002\/ibd.20014","article-title":"Safety and tolerability of concurrent natalizumab treatment for patients with Crohn's disease not in remission while receiving infliximab","volume":"13","author":"Sands","year":"2007","journal-title":"Inflamm. Bowel Dis."},{"issue":"5","key":"10.1016\/j.jaut.2024.103331_bib35","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1093\/rheumatology\/keac584","article-title":"Comorbidities and extra-articular manifestations in difficult-to-treat rheumatoid arthritis: different sides of the same coin?","volume":"62","author":"Dey","year":"2023","journal-title":"Rheumatology"},{"issue":"4","key":"10.1016\/j.jaut.2024.103331_bib36","doi-asserted-by":"crossref","DOI":"10.1016\/j.autrev.2021.102776","article-title":"Rheumatoid arthritis: extra-articular manifestations and comorbidities","volume":"20","author":"Figus","year":"2021","journal-title":"Autoimmun. Rev."},{"issue":"6","key":"10.1016\/j.jaut.2024.103331_bib37","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1136\/annrheumdis-2017-212825","article-title":"Serious infection across biologic-treated patients with rheumatoid arthritis: results from the British society for rheumatology biologics register for rheumatoid arthritis","volume":"77","author":"Rutherford","year":"2018","journal-title":"Ann. Rheum. Dis."},{"issue":"2","key":"10.1016\/j.jaut.2024.103331_bib38","first-page":"CD008794","article-title":"Adverse effects of biologics: a network meta-analysis and Cochrane overview","volume":"2011","author":"Singh","year":"2011","journal-title":"Cochrane Database Syst. Rev."},{"issue":"4","key":"10.1016\/j.jaut.2024.103331_bib39","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1056\/NEJMoa2109927","article-title":"Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis","volume":"386","author":"Ytterberg","year":"2022","journal-title":"N. Engl. J. Med."},{"issue":"3","key":"10.1016\/j.jaut.2024.103331_bib40","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1038\/s41575-022-00722-7","article-title":"Risk minimization of JAK inhibitors in ulcerative colitis following regulatory guidance","volume":"20","author":"Danese","year":"2023","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"issue":"3","key":"10.1016\/j.jaut.2024.103331_bib41","doi-asserted-by":"crossref","DOI":"10.1136\/rmdopen-2020-001395","article-title":"Long-term safety of tofacitinib up to 9.5 years: a comprehensive integrated analysis of the rheumatoid arthritis clinical development programme","volume":"6","author":"Cohen","year":"2020","journal-title":"RMD Open"},{"issue":"4","key":"10.1016\/j.jaut.2024.103331_bib42","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1111\/apt.16712","article-title":"Safety and efficacy of tofacitinib for treatment of ulcerative colitis: final analysis of OCTAVE Open, an open-label, long-term extension study with up to 7.0 years of treatment","volume":"55","author":"Sandborn","year":"2022","journal-title":"Aliment. Pharmacol. Ther."},{"issue":"3","key":"10.1016\/j.jaut.2024.103331_bib43","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.dld.2005.09.020","article-title":"Lessons for inflammatory bowel disease from rheumatology","volume":"38","author":"Rhodes","year":"2006","journal-title":"Dig. Liver Dis."},{"issue":"7","key":"10.1016\/j.jaut.2024.103331_bib44","doi-asserted-by":"crossref","first-page":"1774","DOI":"10.1016\/S0016-5085(03)00382-2","article-title":"Infliximab but not etanercept induces apoptosis in lamina propria T-lymphocytes from patients with Crohn's disease","volume":"124","author":"Van den Brande","year":"2003","journal-title":"Gastroenterology"},{"issue":"8","key":"10.1016\/j.jaut.2024.103331_bib45","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1136\/ard-2022-223757","article-title":"Distinct immune modulatory roles of regulatory T cells in gut versus joint inflammation in TNF-driven spondyloarthritis","volume":"82","author":"Venken","year":"2023","journal-title":"Ann. Rheum. Dis."},{"key":"10.1016\/j.jaut.2024.103331_bib46","doi-asserted-by":"crossref","unstructured":"Desai P BP, Richards D, Vetter M, Cua D, Freeman T. . Differential and combinatorial mechanism of action of golimumab and guselkumab in ulcerative colitis induction therapy: il-23 blockade drives restoration of normal epithelium and mucosal healing. United European Gastroenterol J2022.","DOI":"10.14309\/01.ajg.0000902200.99170.8c"},{"issue":"supplement 8","key":"10.1016\/j.jaut.2024.103331_bib47","first-page":"2022","article-title":"Differential and combinatorial mechanism of action of golimumab and guselkumab in ulcerative colitis induction therapy: il-23 blockade drives restoration of normal epithelium and mucosal healing","volume":"10","author":"Desai","year":"2022","journal-title":"United European Gastroenterol J"},{"issue":"2","key":"10.1016\/j.jaut.2024.103331_bib48","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1053\/j.gastro.2021.04.068","article-title":"Rational combination therapy to overcome the plateau of drug efficacy in inflammatory bowel disease","volume":"161","author":"Stalgis","year":"2021","journal-title":"Gastroenterology"},{"key":"10.1016\/j.jaut.2024.103331_bib49","article-title":"Vedolizumab, adalimumab, and methotrexate combination therapy in Crohn's disease (EXPLORER)","author":"Colombel","year":"2023","journal-title":"Clin. Gastroenterol. Hepatol."}],"container-title":["Journal of Autoimmunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0896841124001653?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0896841124001653?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,2,2]],"date-time":"2025-02-02T06:41:30Z","timestamp":1738478490000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0896841124001653"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12]]},"references-count":49,"alternative-id":["S0896841124001653"],"URL":"https:\/\/doi.org\/10.1016\/j.jaut.2024.103331","relation":{},"ISSN":["0896-8411"],"issn-type":[{"value":"0896-8411","type":"print"}],"subject":[],"published":{"date-parts":[[2024,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Efficacy and safety of Advanced Combination Treatment in immune-mediated inflammatory disease: A systematic review and meta-analysis of randomized controlled trials","name":"articletitle","label":"Article Title"},{"value":"Journal of Autoimmunity","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jaut.2024.103331","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2024 The Authors. Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}],"article-number":"103331"}}