{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:25:16Z","timestamp":1787030716231,"version":"build-2736575974"},"reference-count":49,"publisher":"The Journal of Rheumatology","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Rheumatol"],"published-print":{"date-parts":[[2010,4]]},"abstract":"<jats:sec>\n                    <jats:title>Objective.<\/jats:title>\n                    <jats:p>To assess safety and clinical outcomes in patients with inflammatory arthritis after intraarticular (IA) injection of rAAV2-TNFR:Fc, a recombinant adeno-associated viral vector containing the human tumor necrosis factor (TNF) receptor-immunoglobulin (IgG1) Fc fusion (TNFR:Fc) gene.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods.<\/jats:title>\n                    <jats:p>\n                      In this phase 1\/2 randomized study, adults with persistent moderate or severe inflammation in a target joint, being treated with or without systemic anti-TNF therapy, received a single IA injection of either rAAV2-TNFR:Fc (1 \u00d7 10\n                      <jats:sup>11<\/jats:sup>\n                      , 1 \u00d7 10\n                      <jats:sup>12<\/jats:sup>\n                      , or 1 \u00d7 10\n                      <jats:sup>13<\/jats:sup>\n                      DNase-resistant particles\/ml joint volume) or placebo, followed by open-label rAAV2-TNFR:Fc 12\u201330 weeks later, depending on when the target joint met predetermined criteria for reinjection.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results.<\/jats:title>\n                    <jats:p>127 subjects received the first injection of blinded study drug; 95 subjects received open-label rAAV2-TNFR:Fc. Administration site reactions, consisting of transient mild to moderate increases in tenderness and swelling of the injected joint, occurred after 23\/191 (12%) rAAV2-TNFR:Fc injections and were dose-dependent. Rates of other adverse events were not dose-dependent. Notable serious adverse events (SAE) included culture-negative septic arthritis in a subject receiving leflunomide and fatal disseminated histoplasmosis considered unrelated to rAAV2-TNFR:Fc in a subject receiving adalimumab. In the phase 2 portion of the study, a 30% decrease in target joint global visual analog scale was observed in 21\/50 (42%) rAAV2-TNFR:Fc subjects and 3\/16 (19%) placebo subjects 12 weeks after first injection (p = 0.14).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion.<\/jats:title>\n                    <jats:p>IA rAAV2-TNFR:Fc resulted in administration site reactions after 12% of injections. A fatal SAE, disseminated histoplasmosis, was considered not related to study agent. Patient-reported outcome measures of clinical response showed greater improvement in treated patients than placebo patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3899\/jrheum.090817","type":"journal-article","created":{"date-parts":[[2009,12,23]],"date-time":"2009-12-23T21:39:22Z","timestamp":1261604362000},"page":"692-703","source":"Crossref","is-referenced-by-count":96,"title":["Safety, Tolerability, and Clinical Outcomes after Intraarticular Injection of a Recombinant Adeno-associated Vector Containing a Tumor Necrosis Factor Antagonist Gene: Results of a Phase 1\/2 Study"],"prefix":"10.3899","volume":"37","author":[{"given":"PHILIP J.","family":"MEASE","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"NATHAN","family":"WEI","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"EDWARD J.","family":"FUDMAN","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ALAN J.","family":"KIVITZ","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JOY","family":"SCHECHTMAN","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ROBERT G.","family":"TRAPP","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"KATHRYN F.","family":"HOBBS","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MARIA","family":"GREENWALD","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ANTONY","family":"HOU","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"STEPHEN A.","family":"BOOKBINDER","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"GALEN E.","family":"GRAHAM","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"CRAIG W.","family":"WIESENHUTTER","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"LARRY","family":"WILLIS","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ERIC M.","family":"RUDERMAN","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JOSEPH Z.","family":"FORSTOT","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MICHAEL J.","family":"MARICIC","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"KATHRYN H.","family":"DAO","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"CHARLES H.","family":"PRITCHARD","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"DARRELL N.","family":"FISKE","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"FRANCIS X.","family":"BURCH","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. 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