{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T12:45:51Z","timestamp":1770468351624,"version":"3.49.0"},"reference-count":49,"publisher":"Elsevier BV","issue":"3","license":[{"start":{"date-parts":[[2025,3,1]],"date-time":"2025-03-01T00:00:00Z","timestamp":1740787200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,3,1]],"date-time":"2025-03-01T00:00:00Z","timestamp":1740787200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/501100006356","name":"Syddansk Universitet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006356","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001275","name":"Oak Foundation","doi-asserted-by":"publisher","award":["OCAY-18-774-OFIL"],"award-info":[{"award-number":["OCAY-18-774-OFIL"]}],"id":[{"id":"10.13039\/100001275","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ard.eular.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Annals of the Rheumatic Diseases"],"published-print":{"date-parts":[[2025,3]]},"DOI":"10.1136\/ard-2024-226129","type":"journal-article","created":{"date-parts":[[2024,11,9]],"date-time":"2024-11-09T06:25:15Z","timestamp":1731133515000},"page":"398-408","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":2,"title":["Influence of study characteristics on harm estimates from randomised controlled trials in patients with inflammatory arthritis receiving biological or synthetic antirheumatic drugs: a meta-epidemiological study"],"prefix":"10.1016","volume":"84","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-5411-1496","authenticated-orcid":false,"given":"Johannes Iuel","family":"Berg","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2857-2484","authenticated-orcid":false,"given":"Sabrina Mai","family":"Nielsen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Esben","family":"Malm","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John P.A.","family":"Ioannidis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel E.","family":"Furst","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\/0000-0001-7766-6167","authenticated-orcid":false,"given":"Peter C.","family":"Taylor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lars Erik","family":"Kristensen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon","family":"Tarp","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0426-4962","authenticated-orcid":false,"given":"Torkell","family":"Ellingsen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6600-0631","authenticated-orcid":false,"given":"Robin","family":"Christensen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1136\/ard-2024-226129_bib1","article-title":"Diagnosis and early management of inflammatory arthritis","volume":"358","author":"Ledingham","year":"2017","journal-title":"BMJ"},{"key":"10.1136\/ard-2024-226129_bib2","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.jaut.2014.01.015","article-title":"The classification and diagnostic criteria of ankylosing spondylitis","volume":"48\u201349","author":"Raychaudhuri","year":"2014","journal-title":"J Autoimmun"},{"key":"10.1136\/ard-2024-226129_bib3","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.smim.2017.09.009","article-title":"LTB 4 and BLT1 in inflammatory arthritis","volume":"33","author":"Miyabe","year":"2017","journal-title":"Semin Immunol"},{"key":"10.1136\/ard-2024-226129_bib4","doi-asserted-by":"crossref","first-page":"2205","DOI":"10.1056\/NEJMra1004965","article-title":"The pathogenesis of rheumatoid arthritis","volume":"365","author":"McInnes","year":"2011","journal-title":"N Engl J Med"},{"key":"10.1136\/ard-2024-226129_bib5","article-title":"Comparative effectiveness of biological medicines in rheumatoid arthritis: systematic review and network meta-analysis including aggregate results from reanalysed individual patient data","volume":"370","author":"Janke","year":"2020","journal-title":"BMJ"},{"key":"10.1136\/ard-2024-226129_bib6","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2019-032552","article-title":"Cost-effectiveness analysis of ixekizumab versus secukinumab in patients with psoriatic arthritis and concomitant moderate-to-severe psoriasis in Spain","volume":"10","author":"Schweikert","year":"2020","journal-title":"BMJ Open"},{"key":"10.1136\/ard-2024-226129_bib7","first-page":"2460","article-title":"Total incidence and distribution of inflammatory joint diseases in a defined population: results from the Kuopio 2000 arthritis survey","volume":"30","author":"Savolainen","year":"2003","journal-title":"J Rheumatol"},{"key":"10.1136\/ard-2024-226129_bib8","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1186\/s13063-017-2396-3","article-title":"Harm, benefit and costs associated with low-dose glucocorticoids added to the treatment strategies for rheumatoid arthritis in elderly patients (GLORIA trial): study protocol for a randomised controlled trial","volume":"19","author":"Hartman","year":"2018","journal-title":"Trials"},{"key":"10.1136\/ard-2024-226129_bib9","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1136\/annrheumdis-2012-202641","article-title":"Effect of tumour necrosis factor blockers on radiographic progression of psoriatic arthritis: a systematic review and meta-analysis of randomised controlled trials","volume":"73","author":"Goulabchand","year":"2014","journal-title":"Ann Rheum Dis"},{"key":"10.1136\/ard-2024-226129_bib10","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0136982","article-title":"Most Trial Eligibility Criteria and Patient Baseline Characteristics Do Not Modify Treatment Effect in Trials Using Targeted Therapies for Rheumatoid Arthritis: A Meta-Epidemiological Study","volume":"10","author":"Christensen","year":"2015","journal-title":"PLoS One"},{"key":"10.1136\/ard-2024-226129_bib11","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1136\/annrheumdis-2014-205322","article-title":"Efficacy of TNF\u03b1 blockers in patients with ankylosing spondylitis and non-radiographic axial spondyloarthritis: a meta-analysis","volume":"74","author":"Callhoff","year":"2015","journal-title":"Ann Rheum Dis"},{"key":"10.1136\/ard-2024-226129_bib12","doi-asserted-by":"crossref","first-page":"781","DOI":"10.7326\/0003-4819-141-10-200411160-00009","article-title":"Better reporting of harms in randomized trials: an extension of the CONSORT statement","volume":"141","author":"Ioannidis","year":"2004","journal-title":"Ann Intern Med"},{"key":"10.1136\/ard-2024-226129_bib13","doi-asserted-by":"crossref","first-page":"2275","DOI":"10.1001\/jama.295.19.2275","article-title":"Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials","volume":"295","author":"Bongartz","year":"2006","journal-title":"JAMA"},{"key":"10.1136\/ard-2024-226129_bib14","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"},{"key":"10.1136\/ard-2024-226129_bib15","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"},{"key":"10.1136\/ard-2024-226129_bib16","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/S0140-6736(14)61704-9","article-title":"Risk of serious infection in biological treatment of patients with rheumatoid arthritis: a systematic review and meta-analysis","volume":"386","author":"Singh","year":"2015","journal-title":"The Lancet"},{"key":"10.1136\/ard-2024-226129_bib17","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1038\/s41584-022-00767-7","article-title":"Oral surveillance and JAK inhibitor safety: the theory of relativity","volume":"18","author":"Winthrop","year":"2022","journal-title":"Nat Rev Rheumatol"},{"key":"10.1136\/ard-2024-226129_bib18","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1136\/annrheumdis-2019-216653","article-title":"Safety of synthetic and biological DMARDs: a systematic literature review informing the 2019 update of the EULAR recommendations for the management of rheumatoid arthritis","volume":"79","author":"Sepriano","year":"2020","journal-title":"Ann Rheum Dis"},{"key":"10.1136\/ard-2024-226129_bib19","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1136\/annrheumdis-2019-216761","article-title":"Incidence of venous and arterial thromboembolic events reported in the tofacitinib rheumatoid arthritis, psoriasis and psoriatic arthritis development programmes and from real-world data","volume":"79","author":"Mease","year":"2020","journal-title":"Ann Rheum Dis"},{"key":"10.1136\/ard-2024-226129_bib20","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1136\/annrheumdis-2012-203116","article-title":"Safety profile of protein kinase inhibitors in rheumatoid arthritis: systematic review and meta-analysis","volume":"73","author":"Salgado","year":"2014","journal-title":"Ann Rheum Dis"},{"key":"10.1136\/ard-2024-226129_bib21","article-title":"ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions","volume":"355","author":"Sterne","year":"2016","journal-title":"BMJ"},{"key":"10.1136\/ard-2024-226129_bib22","article-title":"RoB 2: a revised tool for assessing risk of bias in randomised trials","volume":"366","author":"Sterne","year":"2019","journal-title":"BMJ"},{"key":"10.1136\/ard-2024-226129_bib23","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1136\/bmj.39465.451748.AD","article-title":"Empirical evidence of bias in treatment effect estimates in controlled trials with different interventions and outcomes: meta-epidemiological study","volume":"336","author":"Wood","year":"2008","journal-title":"BMJ"},{"key":"10.1136\/ard-2024-226129_bib24","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1001\/jama.1995.03520290060030","article-title":"Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials","volume":"273","author":"Schulz","year":"1995","journal-title":"JAMA"},{"key":"10.1136\/ard-2024-226129_bib25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3310\/hta16350","article-title":"Influence of reported study design characteristics on intervention effect estimates from randomised controlled trials: combined analysis of meta-epidemiological studies","volume":"16","author":"Savovi\u0107","year":"2012","journal-title":"Health Technol Assess"},{"key":"10.1136\/ard-2024-226129_bib26","doi-asserted-by":"crossref","first-page":"i157","DOI":"10.1136\/bmj.i157","article-title":"PRISMA harms checklist: improving harms reporting in systematic reviews","volume":"352","author":"Zorzela","year":"2016","journal-title":"BMJ"},{"key":"10.1136\/ard-2024-226129_bib27","doi-asserted-by":"crossref","first-page":"E901","DOI":"10.1503\/cmaj.200077","article-title":"Development of the Instrument to assess the Credibility of Effect Modification Analyses (ICEMAN) in randomized controlled trials and meta-analyses","volume":"192","author":"Schandelmaier","year":"2020","journal-title":"CMAJ"},{"key":"10.1136\/ard-2024-226129_bib28","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.jclinepi.2021.03.009","article-title":"Effect Modifiers and Statistical Tests for Interaction in Randomized Trials","volume":"134","author":"Christensen","year":"2021","journal-title":"J Clin Epidemiol"},{"key":"10.1136\/ard-2024-226129_bib29","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: an updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"10.1136\/ard-2024-226129_bib30","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1136\/ebmed-2017-110713","article-title":"Guidelines for reporting meta-epidemiological methodology research","volume":"22","author":"Murad","year":"2017","journal-title":"Evid Based Med"},{"key":"10.1136\/ard-2024-226129_bib31","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2021-049850","article-title":"Risk of harm in synthetic and biological intervention trials in patients with inflammatory arthritis: protocol for a metaepidemiological study focusing on contextual factors","volume":"11","author":"Malm","year":"2021","journal-title":"BMJ Open"},{"key":"10.1136\/ard-2024-226129_bib32","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1136\/bmj.323.7303.42","article-title":"Systematic reviews in health care: Assessing the quality of controlled clinical trials","volume":"323","author":"J\u00fcni","year":"2001","journal-title":"BMJ"},{"key":"10.1136\/ard-2024-226129_bib33","doi-asserted-by":"crossref","DOI":"10.1136\/bmj.d5928","article-title":"The Cochrane Collaboration's tool for assessing risk of bias in randomised trials","volume":"343","author":"Higgins","year":"2011","journal-title":"BMJ"},{"key":"10.1136\/ard-2024-226129_bib34","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1002\/sim.1761","article-title":"What to add to nothing? Use and avoidance of continuity corrections in meta-analysis of sparse data","volume":"23","author":"Sweeting","year":"2004","journal-title":"Stat Med"},{"key":"10.1136\/ard-2024-226129_bib35","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1002\/(SICI)1097-0258(19990215)18:3<321::AID-SIM28>3.0.CO;2-P","article-title":"Meta-analysis: formulating, evaluating, combining, and reporting","volume":"18","author":"Normand","year":"1999","journal-title":"Stat Med"},{"key":"10.1136\/ard-2024-226129_bib36","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1002\/sim.1040","article-title":"Advanced methods in meta-analysis: multivariate approach and meta-regression","volume":"21","author":"van Houwelingen","year":"2002","journal-title":"Stat Med"},{"key":"10.1136\/ard-2024-226129_bib37","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1002\/sim.1187","article-title":"How should meta-regression analyses be undertaken and interpreted?","volume":"21","author":"Thompson","year":"2002","journal-title":"Stat Med"},{"key":"10.1136\/ard-2024-226129_bib38","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1002\/sim.1184","article-title":"Statistical methods for assessing the influence of study characteristics on treatment effects in \u201cmeta-epidemiological\u201d research","volume":"21","author":"Sterne","year":"2002","journal-title":"Stat Med"},{"key":"10.1136\/ard-2024-226129_bib39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v036.i03","article-title":"Conducting Meta-Analyses in R with the metafor Package","volume":"36","author":"Viechtbauer","year":"2010","journal-title":"J Stat Softw"},{"key":"10.1136\/ard-2024-226129_bib40","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1038\/s41591-020-0833-4","article-title":"Efficacy outcomes in phase 2 and phase 3 randomized controlled trials in rheumatology","volume":"26","author":"Kerschbaumer","year":"2020","journal-title":"Nat Med"},{"key":"10.1136\/ard-2024-226129_bib41","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1136\/ard-2022-223349","article-title":"Influence of active versus placebo control on treatment responses in randomised controlled trials in rheumatoid arthritis","volume":"82","author":"Kerschbaumer","year":"2023","journal-title":"Ann Rheum Dis"},{"key":"10.1136\/ard-2024-226129_bib42","article-title":"Why most (but perhaps not all) DMARDs work equally well","volume":"64S","author":"Landew\u00e9","year":"2024","journal-title":"Semin Arthritis Rheum"},{"key":"10.1136\/ard-2024-226129_bib43","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1002\/art.10817","article-title":"Eligibility of patients in routine care for major clinical trials of anti\u2013tumor necrosis factor \u03b1 agents in rheumatoid arthritis","volume":"48","author":"Sokka","year":"2003","journal-title":"Arthritis & Rheumatism"},{"key":"10.1136\/ard-2024-226129_bib44","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1186\/s13063-020-4139-0","article-title":"Exclusion rates in randomized controlled trials of treatments for physical conditions: a systematic review","volume":"21","author":"He","year":"2020","journal-title":"Trials"},{"key":"10.1136\/ard-2024-226129_bib45","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1093\/rheumatology\/ket492","article-title":"What drives the comparative effectiveness of biologics vs. methotrexate in rheumatoid arthritis? Meta-regression and graphical inspection of suspected clinical factors","volume":"53","author":"Kanters","year":"2014","journal-title":"Rheumatology (Oxford)"},{"key":"10.1136\/ard-2024-226129_bib46","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1002\/acr.23016","article-title":"Factors Associated With Sustained Remission in Rheumatoid Arthritis in Patients Treated With Anti\u2013Tumor Necrosis Factor","volume":"69","author":"Hamann","year":"2017","journal-title":"Arthritis Care & Research"},{"key":"10.1136\/ard-2024-226129_bib47","doi-asserted-by":"crossref","first-page":"331","DOI":"10.2147\/CLEP.S129728","article-title":"Effect modification, interaction and mediation: an overview of theoretical insights for clinical investigators","volume":"9","author":"Corraini","year":"2017","journal-title":"Clin Epidemiol"},{"key":"10.1136\/ard-2024-226129_bib48","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1136\/ebmed-2017-110715","article-title":"Quality of reporting of harms in randomised controlled trials of pharmacological interventions for rheumatoid arthritis: a systematic review","volume":"22","author":"Hadi","year":"2017","journal-title":"Evid Based Med"},{"key":"10.1136\/ard-2024-226129_bib49","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.jclinepi.2020.03.023","article-title":"Paper 3: Causal inference from meta-epidemiology: a reasonable goal, or wishful thinking","volume":"123","author":"Christensen","year":"2020","journal-title":"J Clin Epidemiol"}],"container-title":["Annals of the Rheumatic Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0003496724148431?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0003496724148431?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/ard-2024-226129","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T00:15:00Z","timestamp":1750896900000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0003496724148431"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3]]},"references-count":49,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,3]]}},"alternative-id":["S0003496724148431"],"URL":"https:\/\/doi.org\/10.1136\/ard-2024-226129","relation":{},"ISSN":["0003-4967"],"issn-type":[{"value":"0003-4967","type":"print"}],"subject":[],"published":{"date-parts":[[2025,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Influence of study characteristics on harm estimates from randomised controlled trials in patients with inflammatory arthritis receiving biological or synthetic antirheumatic drugs: a meta-epidemiological study","name":"articletitle","label":"Article Title"},{"value":"Annals of the Rheumatic Diseases","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1136\/ard-2024-226129","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2024 Published by Elsevier B.V. on behalf of European Alliance of Associations for Rheumatology (EULAR).","name":"copyright","label":"Copyright"}]}}