{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T22:17:22Z","timestamp":1768342642897,"version":"3.49.0"},"reference-count":20,"publisher":"BMJ","issue":"2","license":[{"start":{"date-parts":[[2024,5,24]],"date-time":"2024-05-24T00:00:00Z","timestamp":1716508800000},"content-version":"unspecified","delay-in-days":23,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2024,5,6]]},"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>Obesity and age are strongly linked to severe COVID-19 pneumonia where immunomodulatory agents including Janus kinase inhibitors have shown benefits but the efficacy of such therapy in viral pneumonia is not well understood. We evaluated the impact of obesity and age on survival following baricitinib therapy for severe COVID-19.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>A post hoc analysis of the COV-BARRIER multicentre double-blind randomised study of baricitinib versus placebo (PBO) with an assessment of 28-day mortality was performed. All-cause mortality by day 28 was evaluated in a Cox regression analysis (adjusted to age) in three different groups according to body mass index (BMI) (&lt;25\u2009kg\/m<jats:sup>2<\/jats:sup>, 25\u201330\u2009kg\/m<jats:sup>2<\/jats:sup> and &gt;30\u2009kg\/m<jats:sup>2<\/jats:sup>) and age &lt;65 years and \u226565 years.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In the high BMI group (&gt;25\u2009kg\/m<jats:sup>2<\/jats:sup>), baricitinib therapy showed a significant survival advantage compared with PBO (incidence rate ratio (IRR) for mortality by day 28 0.53 (95% CI 0.32 to 0.87)) and 0.66 (95% CI 0.46 to 0.94) for the respective &lt;65 years and \u226565 years, respectively. The 28-day all-cause-mortality rates for BMI over 30 were 5.62% for baricitinib and 9.22% for PBO (HR=0.6, p&lt;0.05). For BMI under 25\u2009kg\/m<jats:sup>2<\/jats:sup>, irrespective of age, baricitinib therapy conferred no survival advantage (IRR of 1.89 (95% CI 0.49 to 7.28) and 0.95 (95% CI 0.46 to 1.99) for &lt;65\u2009years and \u226565\u2009years, respectively) ((mortality 6.6% baricitinib vs 8.1 in PBO), p&gt;0.05).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>The efficacy of baricitinib in COVID-19 pneumonia is linked to obesity suggesting that immunomodulatory therapy benefit is associated with obesity-associated inflammation.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/rmdopen-2023-004045","type":"journal-article","created":{"date-parts":[[2024,5,24]],"date-time":"2024-05-24T23:30:14Z","timestamp":1716593414000},"page":"e004045","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Pronounced benefits of JAK inhibition with baricitinib in COVID-19 pneumonia in obese but not lean subjects"],"prefix":"10.1136","volume":"10","clinical-trial-number":[{"clinical-trial-number":"nct04421027","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct04421027","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0075-5895","authenticated-orcid":false,"given":"Paula","family":"David","sequence":"first","affiliation":[{"name":"Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK"},{"name":"Internal Medicine B, Sheba Medical Center, Tel Hashomer, Israel"},{"name":"Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Or","family":"Hen","sequence":"additional","affiliation":[{"name":"Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK"},{"name":"Internal Medicine C, Shena Medical Center - Tel Hashomer, Ramat Gan, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niv","family":"Ben-Shabbat","sequence":"additional","affiliation":[{"name":"Internal Medicine B, Sheba Medical Center, Tel Hashomer, Israel"},{"name":"Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tom","family":"Macleod","sequence":"additional","affiliation":[{"name":"Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Howard","family":"Amital","sequence":"additional","affiliation":[{"name":"Internal Medicine B, Sheba Medical Center, Tel Hashomer, Israel"},{"name":"Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdulla","family":"Watad","sequence":"additional","affiliation":[{"name":"Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK"},{"name":"Internal Medicine B, Sheba Medical Center, Tel Hashomer, Israel"},{"name":"Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dennis G","family":"McGonagle","sequence":"additional","affiliation":[{"name":"Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK"},{"name":"NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, England"},{"name":"Leeds Teaching Hospitals NHS Trust, Leeds, England"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2024,5,24]]},"reference":[{"key":"2025090313480250000_10.2.e004045.1","doi-asserted-by":"crossref","first-page":"135","DOI":"10.5603\/ARM.a2021.0036","article-title":"Predictors of mortality in patients with severe COVID-19 pneumonia - a retrospective study","volume":"89","author":"Mahendra","year":"2021","journal-title":"Adv Respir Med"},{"key":"2025090313480250000_10.2.e004045.2","doi-asserted-by":"publisher","DOI":"10.1016\/s2665-9913(20)30121-1"},{"key":"2025090313480250000_10.2.e004045.3","doi-asserted-by":"crossref","first-page":"100007","DOI":"10.1016\/j.tru.2020.100007","article-title":"Monocytes could be a bridge from inflammation to thrombosis on COVID-19 injury: A case report","volume":"1","author":"Mazzone","year":"2020","journal-title":"Thromb Update"},{"key":"2025090313480250000_10.2.e004045.4","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.medin.2023.08.010","article-title":"Association of obesity on the outcome of critically ill patients affected by COVID-19","volume":"48","author":"Rodr\u00edguez","year":"2024","journal-title":"Med Intensiva (Engl Ed)"},{"key":"2025090313480250000_10.2.e004045.5","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2031994"},{"key":"2025090313480250000_10.2.e004045.6","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1016\/S2213-2600(21)00331-3","article-title":"Efficacy and safety of Baricitinib for the treatment of hospitalised adults with COVID-19 (COV-BARRIER): a randomised, double-blind, parallel-group, placebo-controlled phase 3 trial","volume":"9","author":"Marconi","year":"2021","journal-title":"Lancet Respir Med"},{"key":"2025090313480250000_10.2.e004045.7","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)00676-0"},{"key":"2025090313480250000_10.2.e004045.8","doi-asserted-by":"crossref","first-page":"154408","DOI":"10.1016\/j.metabol.2020.154408","article-title":"Commentary: COVID-19 and obesity Pandemics converge into a Syndemic requiring urgent and Multidisciplinary action","volume":"114","author":"Hill","year":"2021","journal-title":"Metabolism"},{"key":"2025090313480250000_10.2.e004045.9","doi-asserted-by":"crossref","DOI":"10.1016\/j.jcv.2022.105297","article-title":"COVID-19 patient characteristics and time to viral clearance: A retrospective observational study in a Multiethnic population (United Arab Emirates)","volume":"157","author":"Hafez","year":"2022","journal-title":"J Clin Virol"},{"key":"2025090313480250000_10.2.e004045.10","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1007\/s11239-020-02297-z","article-title":"Coagulopathy, endothelial dysfunction, thrombotic microangiopathy and complement activation: potential role of complement system inhibition in COVID-19","volume":"51","author":"Wang","year":"2021","journal-title":"J Thromb Thrombolysis"},{"key":"2025090313480250000_10.2.e004045.11","first-page":"310","article-title":"Tissue oxygenation in morbid obesity \u2013 the physiological and clinical perspective","volume":"3","author":"Alvarez","year":"2013","journal-title":"Trend Anaesth Crit Care"},{"key":"2025090313480250000_10.2.e004045.12","doi-asserted-by":"publisher","DOI":"10.1007\/s40292-016-0133-8"},{"key":"2025090313480250000_10.2.e004045.13","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-05-427708"},{"key":"2025090313480250000_10.2.e004045.14","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1160\/TH14-02-0156","article-title":"Hypercoagulability in overweight and obese subjects who are asymptomatic for thrombotic events","volume":"113","author":"Campello","year":"2015","journal-title":"Thromb Haemost"},{"key":"2025090313480250000_10.2.e004045.15","doi-asserted-by":"publisher","DOI":"10.1136\/ard-2022-223050"},{"key":"2025090313480250000_10.2.e004045.16","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.2020203557"},{"key":"2025090313480250000_10.2.e004045.17","doi-asserted-by":"publisher","DOI":"10.1172\/jci140617"},{"key":"2025090313480250000_10.2.e004045.18","unstructured":"Mei\u00dfner Y , Baganz L , Schneider M , et al . Baricitinib and tofacitinib in real life \u2013 does obesity impact response to Janus kinase inhibitor therapy in rheumatoid arthritis? Arthritis Rheumatol 2018;70."},{"key":"2025090313480250000_10.2.e004045.19","doi-asserted-by":"crossref","DOI":"10.1136\/rmdopen-2020-001486","article-title":"Impact of baseline body mass index on the efficacy and safety of tofacitinib in patients with Psoriatic arthritis","volume":"7","author":"Giles","year":"2021","journal-title":"RMD Open"},{"key":"2025090313480250000_10.2.e004045.20","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1002\/art.42767","article-title":"Poly-refractory rheumatoid arthritis: an uncommon subset of difficult to treat disease with distinct inflammatory and non-inflammatory phenotypes","volume":"76","author":"David","year":"2024","journal-title":"Arthr Rheumatol"}],"container-title":["RMD Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/rmdopen-2023-004045","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T20:48:11Z","timestamp":1756932491000},"score":1,"resource":{"primary":{"URL":"https:\/\/rmdopen.bmj.com\/lookup\/doi\/10.1136\/rmdopen-2023-004045"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5]]},"references-count":20,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2024,5,24]]},"published-print":{"date-parts":[[2024,5]]}},"alternative-id":["10.1136\/rmdopen-2023-004045"],"URL":"https:\/\/doi.org\/10.1136\/rmdopen-2023-004045","relation":{},"ISSN":["2056-5933"],"issn-type":[{"value":"2056-5933","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5]]}}}