{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T17:41:05Z","timestamp":1788716465509,"version":"build-2803163510"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,1,11]],"date-time":"2021-01-11T00:00:00Z","timestamp":1610323200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,1,11]],"date-time":"2021-01-11T00:00:00Z","timestamp":1610323200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100002491","name":"Bristol-Myers Squibb","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100002491","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arthritis Res Ther"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>To evaluate incidence of opportunistic infections (OIs) in patients with rheumatoid arthritis (RA) treated with abatacept in clinical trials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This pooled analysis of 16 randomized, double-blind\/open-label trials, with \u2265\u20091 abatacept (intravenous or subcutaneous) arm, and with\/without placebo control covered cumulative (controlled short-term and open-label long-term) abatacept exposure periods. OIs were analyzed separately in controlled (abatacept and placebo individually) and cumulative periods. OIs were identified using a prespecified list; events were independently adjudicated. Unadjusted incidence rates (IRs; per 100 patient-years) with 95% confidence intervals (CIs) were calculated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In cumulative periods, 7044 patients received abatacept, with a mean (standard deviation) duration of exposure of 36.9 (26.2) months (21,274 patient-years of exposure). IRs (95% CIs) of OIs were 0.17 (0.05\u20130.43) for abatacept and 0.56 (0.22\u20131.15) for placebo during the controlled periods and 0.21 (0.15\u20130.28) for abatacept during the cumulative periods. There was 1 case of tuberculosis in both the abatacept (IR [95% CI] 0.04 [0.00\u20130.24]) and placebo (IR [95% CI] 0.08 [0.00\u20130.44]) groups during the controlled periods; 13 verified tuberculosis cases (IR [95% CI] 0.06 [0.03\u20130.10]) were reported in the cumulative period. Herpes zoster was reported numerically more often with abatacept (IR 1.9 [1.4\u20132.5]), versus placebo (1.7 [1.1\u20132.6]) in the controlled periods; within the cumulative period, herpes zoster IR (95% CI) was 1.53 (1.36\u20131.71) for abatacept-treated patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In controlled periods of the clinical trials, abatacept-treated patients had similarly low rates of OIs compared with placebo-treated patients. Overall, OI rates were similar among abatacept-treated patients in the controlled and cumulative periods and consistent with the ranges reported in the literature.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13075-020-02399-2","type":"journal-article","created":{"date-parts":[[2021,1,11]],"date-time":"2021-01-11T07:19:19Z","timestamp":1610349559000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Risk of opportunistic infections in patients with rheumatoid arthritis initiating abatacept: cumulative clinical trial data"],"prefix":"10.1186","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4042-0715","authenticated-orcid":false,"given":"Teresa A.","family":"Simon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixian","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin L.","family":"Winthrop","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,1,11]]},"reference":[{"key":"2399_CR1","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1002\/acr.22470","volume":"67","author":"H Yun","year":"2015","unstructured":"Yun H, Xie F, Delzell E, Chen L, Levitan EB, Lewis JD, et al. Risks of herpes zoster in patients with rheumatoid arthritis according to biologic disease-modifying therapy. Arthritis Care Res (Hoboken). 2015;67:731\u20136.","journal-title":"Arthritis Care Res (Hoboken)"},{"key":"2399_CR2","doi-asserted-by":"crossref","unstructured":"Winthrop KL, Novosad SA, Baddley JW, Calabrese L, Chiller T, Polgreen P, et al. Opportunistic infections and biologic therapies in immune-mediated inflammatory diseases: consensus recommendations for infection reporting during clinical trials and postmarketing surveillance. Ann Rheum Dis. 2015;74:2107\u201316.","DOI":"10.1136\/annrheumdis-2015-207841"},{"key":"2399_CR3","doi-asserted-by":"publisher","first-page":"1843","DOI":"10.1136\/annrheumdis-2016-209131","volume":"75","author":"JR Curtis","year":"2016","unstructured":"Curtis JR, Xie F, Yun H, Bernatsky S, Winthrop KL. Real-world comparative risks of herpes virus infections in tofacitinib and biologic-treated patients with rheumatoid arthritis. Ann Rheum Dis. 2016;75:1843\u20137.","journal-title":"Ann Rheum Dis"},{"key":"2399_CR4","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/s13075-017-1496-5","volume":"20","author":"LR Harrold","year":"2018","unstructured":"Harrold LR, Litman HJ, Saunders KC, Dandreo KJ, Gershenson B, Greenberg JD, et al. One-year risk of serious infection in patients treated with certolizumab pegol as compared with other TNF inhibitors in a real-world setting: data from a national U.S. rheumatoid arthritis registry. Arthritis Res Ther. 2018;20:2.","journal-title":"Arthritis Res Ther."},{"key":"2399_CR5","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1007\/s40744-018-0097-3","volume":"5","author":"S Cohen","year":"2018","unstructured":"Cohen S, Curtis JR, DeMasi R, Chen Y, Fan H, Soonasra A, et al. Worldwide, 3-year, post-marketing surveillance experience with tofacitinib in rheumatoid arthritis. Rheumatol Ther. 2018;5:283\u201391.","journal-title":"Rheumatol Ther"},{"key":"2399_CR6","doi-asserted-by":"publisher","first-page":"1719","DOI":"10.1007\/s00296-017-3772-8","volume":"37","author":"BE Tan","year":"2017","unstructured":"Tan BE, Lim AL, Kan SL, Lim CH, Tsang EEL, Ch'ng SS, et al. Real-world clinical experience of biological disease modifying anti-rheumatic drugs in Malaysia rheumatoid arthritis patients. Rheumatol Int. 2017;37:1719\u201325.","journal-title":"Rheumatol Int"},{"key":"2399_CR7","doi-asserted-by":"publisher","first-page":"1888","DOI":"10.1002\/acr.22912","volume":"68","author":"LR Harrold","year":"2016","unstructured":"Harrold LR, Reed GW, Karki C, Magner R, Shewade A, John A, et al. Risk of infection associated with subsequent biologic agent use after rituximab: results from a national rheumatoid arthritis patient registry. Arthritis Care Res (Hoboken). 2016;68:1888\u201393.","journal-title":"Arthritis Care Res (Hoboken)"},{"key":"2399_CR8","doi-asserted-by":"crossref","unstructured":"Simon TA,\u00a0Boers M, Hochberg M, Baker N, Skovron ML, Ray N, et al.\u00a0Comparative risk of malignancies and infections in patients with rheumatoid arthritis initiating abatacept versus other biologics: a multi-database real-world study. Arthritis Res Ther. 2019;21:228.","DOI":"10.1186\/s13075-019-1992-x"},{"key":"2399_CR9","doi-asserted-by":"publisher","first-page":"758","DOI":"10.1016\/j.autrev.2013.01.001","volume":"12","author":"M Cutolo","year":"2013","unstructured":"Cutolo M, Nadler S. Advances in CTLA-4-Ig-mediated modulation of inflammatory cell and immune response activation in rheumatoid arthritis. Autoimmun Rev. 2013;12:758\u201367.","journal-title":"Autoimmun Rev"},{"key":"2399_CR10","doi-asserted-by":"publisher","first-page":"1907","DOI":"10.1056\/NEJMoa035075","volume":"349","author":"JM Kremer","year":"2003","unstructured":"Kremer JM, Westhovens R, Leon M, Di Giorgio E, Alten R, Steinfeld S, et al. Treatment of rheumatoid arthritis by selective inhibition of T-cell activation with fusion protein CTLA4Ig. N Engl J Med. 2003;349:1907\u201315.","journal-title":"N Engl J Med"},{"key":"2399_CR11","doi-asserted-by":"publisher","first-page":"865","DOI":"10.7326\/0003-4819-144-12-200606200-00003","volume":"144","author":"JM Kremer","year":"2006","unstructured":"Kremer JM, Genant HK, Moreland LW, Russell AS, Emery P, Abud-Mendoza C, et al. Effects of abatacept in patients with methotrexate-resistant active rheumatoid arthritis: a randomized trial. Ann Intern Med. 2006;144:865\u201376.","journal-title":"Ann Intern Med"},{"key":"2399_CR12","doi-asserted-by":"publisher","first-page":"1084","DOI":"10.1136\/ard.2007.085084","volume":"67","author":"HK Genant","year":"2008","unstructured":"Genant HK, Peterfy CG, Westhovens R, Becker JC, Aranda R, Vratsanos G, et al. Abatacept inhibits progression of structural damage in rheumatoid arthritis: results from the long-term extension of the AIM trial. Ann Rheum Dis. 2008;67:1084\u20139.","journal-title":"Ann Rheum Dis"},{"key":"2399_CR13","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1136\/ard.2007.074773","volume":"67","author":"MC Genovese","year":"2008","unstructured":"Genovese MC, Schiff M, Luggen M, Becker JC, Aranda R, Teng J, et al. Efficacy and safety of the selective co-stimulation modulator abatacept following 2 years of treatment in patients with rheumatoid arthritis and an inadequate response to anti-tumour necrosis factor therapy. Ann Rheum Dis. 2008;67:547\u201354.","journal-title":"Ann Rheum Dis"},{"key":"2399_CR14","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1136\/annrheumdis-2013-203843","volume":"73","author":"M Schiff","year":"2014","unstructured":"Schiff M, Weinblatt ME, Valente R, van der Heijde D, Citera G, Elegbe A, et al. Head-to-head comparison of subcutaneous abatacept versus adalimumab for rheumatoid arthritis: two-year efficacy and safety findings from AMPLE trial. Ann Rheum Dis. 2014;73:86\u201394.","journal-title":"Ann Rheum Dis"},{"key":"2399_CR15","doi-asserted-by":"publisher","first-page":"1096","DOI":"10.1136\/ard.2007.080002","volume":"67","author":"M Schiff","year":"2008","unstructured":"Schiff M, Keiserman M, Codding C, Songcharoen S, Berman A, Nayiager S, et al. Efficacy and safety of abatacept or infliximab vs placebo in ATTEST: a phase III, multi-centre, randomised, double-blind, placebo-controlled study in patients with rheumatoid arthritis and an inadequate response to methotrexate. Ann Rheum Dis. 2008;67:1096\u2013103.","journal-title":"Ann Rheum Dis"},{"key":"2399_CR16","doi-asserted-by":"publisher","first-page":"R67","DOI":"10.1186\/ar2984","volume":"12","author":"TA Simon","year":"2010","unstructured":"Simon TA, Askling J, Lacaille D, Franklin J, Wolfe F, Covucci A, et al. Infections requiring hospitalization in the abatacept clinical development program: an epidemiological assessment. Arthritis Res Ther. 2010;12:R67.","journal-title":"Arthritis Res Ther."},{"key":"2399_CR17","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1002\/acr2.1034","volume":"1","author":"T Simon","year":"2019","unstructured":"Simon T, Soule B, Hochberg M, Fleming D, Torbeyns A, Banerjee S, et al. Safety of abatacept versus placebo in rheumatoid arthritis: integrated data analysis of nine clinical trials. ACR Open Rheumatol. 2019;1:251\u20137.","journal-title":"ACR Open Rheumatol"},{"key":"2399_CR18","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1002\/art.1780310302","volume":"31","author":"FC Arnett","year":"1988","unstructured":"Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheumatol. 1988;31:315\u201324.","journal-title":"Arthritis Rheumatol"},{"key":"2399_CR19","first-page":"199","volume":"47","author":"ICH Harmonised Tripartite Guideline","year":"2001","unstructured":"ICH Harmonised Tripartite Guideline. Guideline for good clinical practice. J Postgrad Med. 2001;47:199\u2013203.","journal-title":"J Postgrad Med"},{"key":"2399_CR20","doi-asserted-by":"publisher","first-page":"1942","DOI":"10.1136\/annrheumdis-2013-203407","volume":"73","author":"JW Baddley","year":"2014","unstructured":"Baddley JW, Winthrop KL, Chen L, Liu L, Grijalva CG, Delzell E, et al. Non-viral opportunistic infections in new users of TNF inhibitor therapy: results of the SAfety assessment of biologic thERapy (SABER) study. Ann Rheum Dis. 2014;73:1942.","journal-title":"Ann Rheum Dis"},{"key":"2399_CR21","doi-asserted-by":"publisher","first-page":"1133","DOI":"10.1136\/annrheumdis-2015-207319","volume":"75","author":"KL Winthrop","year":"2016","unstructured":"Winthrop KL, Park SH, Gul A, Cardiel MH, Gomez-Reino JJ, Tanaka Y, et al. Tuberculosis and other opportunistic infections in tofacitinib-treated patients with rheumatoid arthritis. Ann Rheum Dis. 2016;75:1133\u20138.","journal-title":"Ann Rheum Dis"},{"key":"2399_CR22","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1007\/s00535-012-0686-9","volume":"48","author":"M Naganuma","year":"2013","unstructured":"Naganuma M, Kunisaki R, Yoshimura N, Takeuchi Y, Watanabe M. A prospective analysis of the incidence of and risk factors for opportunistic infections in patients with inflammatory bowel disease. J Gastroenterol. 2013;48:595\u2013600.","journal-title":"J Gastroenterol"},{"key":"2399_CR23","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1007\/s10096-008-0628-x","volume":"28","author":"C Garcia-Vidal","year":"2009","unstructured":"Garcia-Vidal C, Rodriguez-Fernandez S, Teijon S, Esteve M, Rodriguez-Carballeira M, Lacasa JM, et al. Risk factors for opportunistic infections in infliximab-treated patients: the importance of screening in prevention. Eur Clin Microbiol Infectious Dis. 2009;28:331\u20137.","journal-title":"Eur Clin Microbiol Infectious Dis"},{"key":"2399_CR24","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1136\/ard.2010.137422","volume":"70","author":"D Salmon-Ceron","year":"2011","unstructured":"Salmon-Ceron D, Tubach F, Lortholary O, Chosidow O, Bretagne S, Nicolas N, et al. Drug-specific risk of non-tuberculosis opportunistic infections in patients receiving anti-TNF therapy reported to the 3-year prospective French RATIO registry. Ann Rheum Dis. 2011;70:616\u201323.","journal-title":"Ann Rheum Dis"},{"key":"2399_CR25","doi-asserted-by":"publisher","first-page":"1554","DOI":"10.1053\/j.gastro.2020.01.001","volume":"158","author":"PA Olivera","year":"2020","unstructured":"Olivera PA, Lasa JS, Bonovas S, Danese S, Peyrin-Biroulet L. Safety of Janus kinase inhibitors in patients with inflammatory bowel diseases or other immune-mediated diseases: a systematic review and meta-analysis. Gastroenterology. 2020;158:1554\u201373.e12.","journal-title":"Gastroenterology"},{"key":"2399_CR26","doi-asserted-by":"publisher","first-page":"2003","DOI":"10.1136\/annrheumdis-2011-200316","volume":"70","author":"M Schiff","year":"2011","unstructured":"Schiff M, Keiserman M, Codding C, Songcharoen S, Berman A, Nayiager S, et al. Clinical response and tolerability to abatacept in patients with rheumatoid arthritis previously treated with infliximab or abatacept: open-label extension of the ATTEST Study. Ann Rheum Dis. 2011;70:2003\u20137.","journal-title":"Ann Rheum Dis"},{"key":"2399_CR27","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1002\/art.37711","volume":"65","author":"ME Weinblatt","year":"2013","unstructured":"Weinblatt ME, Schiff M, Valente R, van der Heijde D, Citera G, Zhao C, et al. Head-to-head comparison of subcutaneous abatacept versus adalimumab for rheumatoid arthritis: findings of a phase IIIb, multinational, prospective, randomized study. Arthritis Rheum. 2013;65:28\u201338.","journal-title":"Arthritis Rheum"},{"key":"2399_CR28","doi-asserted-by":"publisher","first-page":"1212","DOI":"10.1136\/annrheumdis-2013-204960","volume":"74","author":"EV Arkema","year":"2015","unstructured":"Arkema EV, Jonsson J, Baecklund E, Bruchfeld J, Feltelius N, Askling J. Are patients with rheumatoid arthritis still at an increased risk of tuberculosis and what is the role of biological treatments? Ann Rheum Dis. 2015;74:1212\u20137.","journal-title":"Ann Rheum Dis"},{"key":"2399_CR29","doi-asserted-by":"crossref","unstructured":"Simon TA, Suissa S, Skovron ML, Frisell T, Askling J, Michaud K, et al.\u00a0Infection outcomes in patients with RA treated with abatacept and other DMARDs: results from a 10-year international post-approval study. EULAR Annual European Congress of Rheumatology; Madrid, Spain; 2019. Poster FRI0118.","DOI":"10.1136\/annrheumdis-2019-eular.1725"},{"key":"2399_CR30","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.1136\/annrheumdis-2016-210708","volume":"76","author":"S Ramiro","year":"2017","unstructured":"Ramiro S, Sepriano A, Chatzidionysiou K, Nam JL, Smolen JS, van der Heijde D, et al. Safety of synthetic and biological DMARDs: a systematic literature review informing the 2016 update of the EULAR recommendations for management of rheumatoid arthritis. Ann Rheum Dis. 2017;76:1101\u201336.","journal-title":"Ann Rheum Dis"},{"key":"2399_CR31","unstructured":"Orencia prescribing information. 2017. http:\/\/packageinserts.bms.com\/pi\/pi_orencia.pdf. Accessed 3 Mar 2020."},{"key":"2399_CR32","doi-asserted-by":"publisher","first-page":"976","DOI":"10.1136\/ard.2009.126573","volume":"69","author":"JL Nam","year":"2010","unstructured":"Nam JL, Winthrop KL, van Vollenhoven RF, Pavelka K, Valesini G, Hensor EM, et al. Current evidence for the management of rheumatoid arthritis with biological disease-modifying antirheumatic drugs: a systematic literature review informing the EULAR recommendations for the management of RA. Ann Rheum Dis. 2010;69:976\u201386.","journal-title":"Ann Rheum Dis"},{"key":"2399_CR33","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1186\/s13075-019-1992-x","volume":"21","author":"TA Simon","year":"2019","unstructured":"Simon TA, Boers M, Hochberg M, Baker N, Skovron ML, Ray N, et al. Comparative risk of malignancies and infections in patients with rheumatoid arthritis initiating abatacept versus other biologics: a multi-database real-world study. Arthritis Res Ther. 2019;21:228.","journal-title":"Arthritis Res Ther"},{"key":"2399_CR34","doi-asserted-by":"publisher","first-page":"963","DOI":"10.1136\/annrheumdis-2013-204948","volume":"74","author":"MH Buch","year":"2015","unstructured":"Buch MH, Silva-Fernandez L, Carmona L, Aletaha D, Christensen R, Combe B, et al. Development of EULAR recommendations for the reporting of clinical trial extension studies in rheumatology. Ann Rheum Dis. 2015;74:963\u20139.","journal-title":"Ann Rheum Dis"},{"key":"2399_CR35","doi-asserted-by":"publisher","first-page":"S633","DOI":"10.1002\/art.24363","volume":"60","author":"P Nash","year":"2009","unstructured":"Nash P, Nayiager S, Genovese M, Kivitz A, Oelke K, Ludivico C, et al. Immunogenicity is not increased with subcutaneous administration of abatacept with and without methotrexate in patients with rheumatoid arthritis: results from a phase III study. Arthritis Rheum. 2009;60:S633\u20134.","journal-title":"Arthritis Rheum"},{"key":"2399_CR36","first-page":"iii97","volume":"69","author":"P Nash","year":"2010","unstructured":"Nash P, Nayiager S, Genovese M, Rodriguez C, Delaet I, Elegbe A, et al. Low immunogenicity, consistent safety and sustained clinical efficacy over 18 months of subcutaneous administration of abatacept with and without methotrexate in patients with rheumatoid arthritis-results from a phase III study. Ann Rheum Dis. 2010;69:iii97.","journal-title":"Ann Rheum Dis"}],"container-title":["Arthritis Research &amp; Therapy"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13075-020-02399-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s13075-020-02399-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13075-020-02399-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,1,11]],"date-time":"2021-01-11T08:13:00Z","timestamp":1610352780000},"score":1,"resource":{"primary":{"URL":"https:\/\/arthritis-research.biomedcentral.com\/articles\/10.1186\/s13075-020-02399-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,11]]},"references-count":36,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["2399"],"URL":"https:\/\/doi.org\/10.1186\/s13075-020-02399-2","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-16479\/v1","asserted-by":"object"},{"id-type":"doi","id":"10.21203\/rs.3.rs-16479\/v2","asserted-by":"object"},{"id-type":"doi","id":"10.21203\/rs.3.rs-16479\/v3","asserted-by":"object"}]},"ISSN":["1478-6362"],"issn-type":[{"value":"1478-6362","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,11]]},"assertion":[{"value":"3 March 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 December 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 January 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Not applicable","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"TAS: employee and shareholder of Bristol Myers Squibb (at the time of the analysis; a former employee at present); LD: employee and shareholder of Bristol Myers Squibb; KLW: research grants: Bristol Myers Squibb and Pfizer; Consulting fees: AbbVie (>$10,000), Bristol Myers Squibb, Gilead, Lily, Pfizer and UCB.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"17"}}