{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T12:32:35Z","timestamp":1792672355427,"version":"4.5.0"},"reference-count":9,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100004331","name":"johnson and johnson","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004331","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Therapeutic Advances in Musculoskeletal"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Programmed cell death protein 1 (PD-1) is associated with the immunopathology of rheumatoid arthritis (RA). JNJ-67484703 is a humanized IgG anti-PD-1 agonist antibody.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives:<\/jats:title>\n                    <jats:p>To report results of a phase Ib study evaluating the safety, tolerability, and disease-related outcomes of JNJ-67484703 in adults with active rheumatoid arthritis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design:<\/jats:title>\n                    <jats:p>A randomized, double-blind, placebo-controlled, multiple-dose, phase Ib study in adults with active RA who were inadequately controlled on conventional synthetic disease-modifying antirheumatic drugs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      JNJ-67484703 at doses of 2 or 3\u2009mg\/kg or placebo was administered by subcutaneous injection for 10\u2009weeks (on weeks 0, 1, 2, 4, 6, 8, and 10). Safety was assessed for the first 6 participants in the 2\u2009mg\/kg group to determine if enrollment would proceed to the 3\u2009mg\/kg dose. The primary endpoint was the proportion of participants with treatment-emergent adverse events (TEAEs). Secondary endpoints included change from baseline at week 12 in Disease Activity Score 28 using C-reactive protein (DAS28-CRP) and circulating PD-1\n                      <jats:sup>+<\/jats:sup>\n                      T-cell counts at the 3\u2009mg\/kg dose level only. Least squares (LS) mean difference between JNJ-67484703 groups and placebo were based on mixed-effect model for repeated measures for DAS28-CRP.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      A total of 44 participants were randomized to receive JNJ-67484703 2\u2009mg\/kg (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      \u2009=\u20095), 3\u2009mg\/kg (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      \u2009=\u200925), or placebo (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      \u2009=\u200914); TEAEs were reported in 4 (80%), 17 (68%), and 10 (71%), respectively. None were severe in intensity, and no deaths were reported. TEAEs of infection were reported in 21% of placebo participants and 20% of those in the combined JNJ-67484703 groups. No injection-site or hypersensitivity reactions were reported. At week 12, reduction in DAS28-CRP from baseline was numerically greater in the JNJ-67484703 2\u2009mg\/kg and 3\u2009mg\/kg groups versus placebo, with a difference in LS means between the 3\u2009mg\/kg group and placebo of \u22120.69 (95% CI \u22121.55, 0.18;\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.117). JNJ-67484703 decreased circulating PD-1\n                      <jats:sup>+<\/jats:sup>\n                      T cells, with the greatest effect on those with the highest baseline expression of PD-1.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>JNJ-67484703 was well tolerated in participants with active RA and showed evidence for biologic and clinical activity in this small, proof-of-mechanism study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration:<\/jats:title>\n                    <jats:p>ClinicalTrials.gov, NCT04985812.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/1759720x251385857","type":"journal-article","created":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T14:30:28Z","timestamp":1761057028000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":7,"title":["Safety, tolerability, and efficacy of the PD-1 agonist antibody JNJ-67484703 in adults with active rheumatoid arthritis: results of a multicenter, double-blind, placebo-controlled, randomized, multiple-dose phase Ib study"],"prefix":"10.1177","volume":"17","author":[{"given":"Irving T. C.","family":"Ling","sequence":"first","affiliation":[{"name":"Johnson &amp; Johnson, Translational Sciences and Medicine, Immunology, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanley J.","family":"Marciniak","sequence":"additional","affiliation":[{"name":"Johnson &amp; Johnson, Translational Sciences and Medicine, Immunology, Spring House, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen H.","family":"Clarke","sequence":"additional","affiliation":[{"name":"Johnson &amp; Johnson, Translational Sciences and Medicine, Immunology, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vani","family":"Lakshminarayanan","sequence":"additional","affiliation":[{"name":"Johnson &amp; Johnson, Translational Sciences and Medicine, Immunology, Spring House, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J.","family":"Loza","sequence":"additional","affiliation":[{"name":"Johnson &amp; Johnson, Translational Sciences and Medicine, Immunology, Spring House, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia G.","family":"Liva","sequence":"additional","affiliation":[{"name":"Johnson &amp; Johnson, Clinical Pharmacology &amp; Pharmacometrics, Spring House, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Wang","sequence":"additional","affiliation":[{"name":"Johnson &amp; Johnson, Statistics and Decision Sciences, Chesterbrook, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Orillion","sequence":"additional","affiliation":[{"name":"Johnson &amp; Johnson, Translational Sciences and Medicine, Immunology, Spring House, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilia","family":"Tikhonov","sequence":"additional","affiliation":[{"name":"Johnson &amp; Johnson, Global Medical Safety, Immunology, Raritan, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5712-3579","authenticated-orcid":false,"given":"Erika H.","family":"Noss","sequence":"additional","affiliation":[{"name":"Johnson &amp; Johnson, Translational Sciences and Medicine, Immunology, 1400 McKeon Rd, Spring House, PA 19477, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,10,21]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2015.02.008"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2010.00923.x"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdx286"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature20810"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1136\/rmdopen-2022-002563"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/iub.2558"},{"key":"e_1_3_4_8_2","article-title":"Immune checkpoint inhibitor PD-1 pathway is down-regulated in synovium at various stages of rheumatoid arthritis disease progression","volume":"13","author":"Guo Y","year":"2018","unstructured":"Guo Y, Walsh AM, Canavan M, et al. Immune checkpoint inhibitor PD-1 pathway is down-regulated in synovium at various stages of rheumatoid arthritis disease progression. PLoS One 2018; 13: e0192704.","journal-title":"PLoS One"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2010.138461"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780360601"}],"container-title":["Therapeutic Advances in Musculoskeletal Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1759720X251385857","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/1759720X251385857","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1759720X251385857","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T22:40:18Z","timestamp":1777588818000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/1759720X251385857"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8]]},"references-count":9,"alternative-id":["10.1177\/1759720X251385857"],"URL":"https:\/\/doi.org\/10.1177\/1759720x251385857","relation":{},"ISSN":["1759-720X","1759-7218"],"issn-type":[{"value":"1759-720X","type":"print"},{"value":"1759-7218","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8]]},"article-number":"1759720X251385857"}}