{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T22:04:28Z","timestamp":1782252268968,"version":"3.54.5"},"reference-count":9,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2015,3,19]],"date-time":"2015-03-19T00:00:00Z","timestamp":1426723200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2015,3,19]],"date-time":"2015-03-19T00:00:00Z","timestamp":1426723200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arthritis Res Ther"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                        <jats:title>Introduction<\/jats:title>\n                        <jats:p>This randomized, double-blind, phase II study evaluated the pharmacodynamics, safety and tolerability of ISIS 329993 (ISIS-CRP<jats:sub>Rx<\/jats:sub>), an antisense oligonucleotide, in patients with active rheumatoid arthritis (RA).<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Methods<\/jats:title>\n                        <jats:p>Patients with active RA of at least six months duration were randomized into three cohorts to receive ISIS-CRP<jats:sub>Rx<\/jats:sub> (100\u00a0mg, 200\u00a0mg or 400\u00a0mg) or placebo (3 active:1 placebo within each cohort) via subcutaneous (SC) injection on Days 1, 3, 5 and 8 and then once weekly for the next 11\u00a0weeks. The effects of study treatment on high-sensitivity C-reactive protein (hs-CRP) level were evaluated. An exploratory analysis on disease activity was assessed via the American College of Rheumatology 20% improvement criteria (ACR20). Safety was evaluated via adverse events and laboratory measures.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Results<\/jats:title>\n                        <jats:p>Fifty-one patients received one of the following treatments: ISIS-CRP<jats:sub>Rx<\/jats:sub> 100\u00a0mg, n\u2009=\u200912; 200\u00a0mg, n\u2009=\u200913, 400\u00a0mg, n\u2009=\u200914; placebo n\u2009=\u200912. In the ISIS-CRP<jats:sub>Rx<\/jats:sub> treatment groups there were dose-dependent reductions in hs-CRP. At Day 36 the mean percent change from baseline was: placebo: \u221214.4%; ISIS-CRP<jats:sub>Rx<\/jats:sub> 100\u00a0mg: \u221219.5%; 200\u00a0mg: \u221256.6% and 400\u00a0mg: \u221276.7%, (<jats:italic>P<\/jats:italic>\u2009=\u20090.0015 placebo compared to 400\u00a0mg). There were no differences between treatment groups and placebo in the ACR20 at Day 36 or Day 92. There were no serious infections and no elevations in liver function tests, lipids, creatinine or other lab abnormalities related to ISIS-CRP<jats:sub>Rx<\/jats:sub>.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Conclusions<\/jats:title>\n                        <jats:p>In this study, ISIS-CRP<jats:sub>Rx<\/jats:sub> selectively reduced hs-CRP in a dose-dependent manner, and was well-tolerated in patients with RA. Its utility as a therapy in RA remains unclear.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Trial registration<\/jats:title>\n                        <jats:p>Clinicaltrials.gov <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT01414101\">NCT01414101<\/jats:ext-link>. Registered 21 July 2011.<\/jats:p>\n                     <\/jats:sec>","DOI":"10.1186\/s13075-015-0578-5","type":"journal-article","created":{"date-parts":[[2015,3,18]],"date-time":"2015-03-18T02:21:34Z","timestamp":1426645294000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Results of a proof of concept, double-blind, randomized trial of a second generation antisense oligonucleotide targeting high-sensitivity C-reactive protein (hs-CRP) in rheumatoid arthritis"],"prefix":"10.1186","volume":"17","author":[{"given":"Marshelle S","family":"Warren","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven G","family":"Hughes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter","family":"Singleton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mason","family":"Yamashita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark C","family":"Genovese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,3,19]]},"reference":[{"key":"578_CR1","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1007\/s00296-007-0357-y","volume":"27","author":"P Emery","year":"2007","unstructured":"Emery P, Gabay C, Kraan M, Gomez-Reino J. Evidence-based review of biologic markers as indicators of disease progression and remission in rheumatoid arthritis. Rheumatol Int. 2007;27:793\u2013806.","journal-title":"Rheumatol Int"},{"key":"578_CR2","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1002\/1529-0131(200105)44:5<997::AID-ANR178>3.0.CO;2-C","volume":"44","author":"ET Molenaar","year":"2001","unstructured":"Molenaar ET, Voskuyl AE, Familian A, van Mierlo GJ, Dijkmans BA, Hack CE. Complement activation in patients with rheumatoid arthritis mediated in part by C-reactive protein. Arthritis Rheum. 2001;44:997\u20131002.","journal-title":"Arthritis Rheum"},{"key":"578_CR3","first-page":"1095","volume":"31","author":"PH Dessein","year":"2004","unstructured":"Dessein PH, Joffe BI, Stanwix AE. High sensitivity C-reactive protein as a disease activity marker in rheumatoid arthritis. 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