{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T06:43:37Z","timestamp":1790664217158,"version":"4.1.0"},"reference-count":54,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2016,7,22]],"date-time":"2016-07-22T00:00:00Z","timestamp":1469145600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis Care &amp; Research"],"published-print":{"date-parts":[[2016,8]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To systematically compare the risk of adverse events (AEs) for 13 targeted immunomodulators (TIMs) indicated for ankylosing spondylitis (AS), inflammatory bowel diseases, juvenile idiopathic arthritis, plaque psoriasis, psoriatic arthritis (PsA), or rheumatoid arthritis (RA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We searched electronic databases through July 2015 to retrieve randomized controlled trials (RCTs) and observational studies comparing AEs between 2 or more TIMs head\u2010to\u2010head. We reported on the following outcomes: number of AEs, discontinuation due to AEs, serious AEs, mortality, serious infections, tuberculosis, herpes zoster, and malignancies. We qualitatively synthesized the literature and conducted random\u2010effects meta\u2010analyses if 3 or more studies provided data for an outcome.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Ten head\u2010to\u2010head RCTs and 51 observational studies were included in this systematic review. A majority of the studies (70%) were conducted in RA patients. Risk of treatment discontinuation due to AEs was higher with infliximab than with adalimumab or etanercept in RA, PsA, and AS. A higher risk for serious infections was noted with infliximab than with abatacept, adalimumab, or etanercept in RA. Risk for treatment discontinuation due to AEs, serious infections, and tuberculosis was lower with etanercept than with adalimumab in RA. Limited evidence suggested no comparative differences in risk for mortality, malignancies, and herpes zoster for adalimumab, etanercept, and infliximab in RA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Important differences were noted in the safety profile of TIMs in RA, generally favoring abatacept, adalimumab, and etanercept over infliximab. Head\u2010to\u2010head comparative evidence for other TIMs and non\u2010RA populations was insufficient to draw conclusions for most of the safety outcomes.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acr.22815","type":"journal-article","created":{"date-parts":[[2015,12,14]],"date-time":"2015-12-14T10:55:33Z","timestamp":1450090533000},"page":"1078-1088","source":"Crossref","is-referenced-by-count":27,"title":["Comparative Risk of Harm Associated With the Use of Targeted Immunomodulators: A Systematic Review"],"prefix":"10.1002","volume":"68","author":[{"given":"Rishi J.","family":"Desai","sequence":"first","affiliation":[{"name":"Brigham and Women's Hospital and Harvard Medical School Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kylie J.","family":"Thaler","sequence":"additional","affiliation":[{"name":"Danube University Krems Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Mahlknecht","sequence":"additional","affiliation":[{"name":"Danube University Krems Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald","family":"Gartlehner","sequence":"additional","affiliation":[{"name":"Danube University, Krems, Austria, and RTI International, Research Triangle Park  North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marian S.","family":"McDonagh","sequence":"additional","affiliation":[{"name":"Pacific Northwest Evidence\u2010Based Practice Center, Oregon Health &amp; Science University Portland Oregon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bita","family":"Mesgarpour","sequence":"additional","affiliation":[{"name":"Digestive Diseases Research Institute, Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alireza","family":"Mazinanian","sequence":"additional","affiliation":[{"name":"Danube University Krems Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Glechner","sequence":"additional","affiliation":[{"name":"Danube University Krems Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandrasekar","family":"Gopalakrishnan","sequence":"additional","affiliation":[{"name":"Brigham and Women's Hospital and Harvard Medical School Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Hansen","sequence":"additional","affiliation":[{"name":"Harrison School of Pharmacy Auburn University Auburn Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,7,22]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/1741-7015-11-88"},{"key":"e_1_2_6_3_1","first-page":"387","article-title":"2009 drug utilization and cost trends: tumor necrosis factor inhibitors","volume":"2","author":"Theodorou AA","year":"2010","journal-title":"Am J Pharm Benefits"},{"key":"e_1_2_6_4_1","volume-title":"Drug therapy for rheumatoid arthritis in adults: an update","author":"Donahue K","year":"2012"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2014.10.011"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2474-15-26"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.12663"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.295.19.2275"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1503\/cmaj.091391"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1185\/03007995.2013.813839"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1345\/aph.1R203"},{"key":"e_1_2_6_12_1","first-page":"CD008794","article-title":"Adverse effects of biologics: a network meta\u2010analysis and Cochrane overview","volume":"2","author":"Singh JA","year":"2011","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0749-3797(01)00261-6"},{"key":"e_1_2_6_14_1","unstructured":"KhanKS ter RietG PopayJ NixonJ KleijnenJ.Undertaking systematic reviews of research on effectiveness CRD's guidance for those carrying out or commissioning reviews. 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