{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T15:16:27Z","timestamp":1790781387191,"version":"4.1.0"},"reference-count":25,"publisher":"The Journal of Rheumatology","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Rheumatol"],"published-print":{"date-parts":[[2015,10]]},"abstract":"<jats:sec><jats:title>Objective.<\/jats:title><jats:p>To assess the efficacy and safety of JNJ-40346527, a selective inhibitor of colony-stimulating factor-1 (CSF-1) receptor kinase that acts to inhibit macrophage survival, proliferation, and differentiation in patients with active rheumatoid arthritis (RA) despite disease-modifying antirheumatic drug (DMARD) therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods.<\/jats:title><jats:p>In this randomized, double-blind, placebo-controlled, parallel group study, adults were randomized (2:1) to receive oral JNJ-40346527 100 mg or placebo twice daily through Week 12. Patients with RA had disease activity [\u2265 6 swollen\/\u2265 6 tender joints, C-reactive protein (CRP) \u2265 0.8 mg\/dl] despite DMARD therapy for \u2265 6 months. The primary endpoint was change from baseline at Week 12 in the 28-joint Disease Activity Score with CRP (DAS28-CRP). Pharmacokinetic\/pharmacodynamic analyses were also performed, and safety was assessed through Week 16.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results.<\/jats:title><jats:p>Ninety-five patients were treated (63 JNJ-40346527, 32 placebo); 8 patients discontinued treatment (6 JNJ-40346527, 2 placebo) through Week 12. Mean improvements in DAS28-CRP from baseline to Week 12 were 1.15 for the JNJ-40346527 group and 1.42 for the placebo group (p = 0.30); thus, a statistically significant difference was not observed for the primary endpoint. Pharmacokinetic exposure to JNJ-40346527 and its active metabolites was above the projected concentration needed for pharmacologic activity, and effective target engagement and proof of activity were demonstrated by increased levels of CSF-1 and decreased CD16+ monocytes in JNJ-40346527\u2013treated, but not placebo-treated, patients. Thirty-seven (58.7%) JNJ-40346527\u2013treated and 16 (50.0%) placebo-treated patients reported \u2265 1 adverse event (AE); 1 (1.6%) JNJ-40346527\u2013treated and 3 (9.4%) placebo-treated patients reported \u2265 1 serious AE.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion.<\/jats:title><jats:p>Although adequate exposure and effective peripheral target engagement were evident, JNJ-40346527 efficacy was not observed in patients with DMARD-refractory active RA. <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"ClinicalTrials.gov\" ext-link-type=\"uri\" xlink:type=\"simple\">ClinicalTrials.gov<\/jats:ext-link> identifier: <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT01597739\">NCT01597739<\/jats:ext-link>. EudraCT Number: 2011-004529-28.<\/jats:p><\/jats:sec>","DOI":"10.3899\/jrheum.141580","type":"journal-article","created":{"date-parts":[[2015,8,2]],"date-time":"2015-08-02T00:30:01Z","timestamp":1438475401000},"page":"1752-1760","source":"Crossref","is-referenced-by-count":67,"title":["Results from a Phase IIA Parallel Group Study of JNJ-40346527, an Oral CSF-1R Inhibitor, in Patients with Active Rheumatoid Arthritis despite Disease-modifying Antirheumatic Drug Therapy"],"prefix":"10.3899","volume":"42","author":[{"given":"Mark C.","family":"Genovese","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Hsia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanley M.","family":"Belkowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caly","family":"Chien","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tara","family":"Masterson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin L.","family":"Thurmond","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl L.","family":"Manthey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu (David)","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Ge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol","family":"Franks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Greenspan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2262","published-online":{"date-parts":[[2015,8,1]]},"reference":[{"key":"2018112909351367000_42.10.1752.1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1004965"},{"key":"2018112909351367000_42.10.1752.2","doi-asserted-by":"publisher","DOI":"10.1002\/acr.21641"},{"key":"2018112909351367000_42.10.1752.3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1303006"},{"key":"2018112909351367000_42.10.1752.4","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)61424-X"},{"key":"2018112909351367000_42.10.1752.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2010.04.002"},{"key":"2018112909351367000_42.10.1752.6","doi-asserted-by":"publisher","DOI":"10.1038\/nri2356"},{"key":"2018112909351367000_42.10.1752.7","doi-asserted-by":"publisher","DOI":"10.1002\/art.38624"},{"key":"2018112909351367000_42.10.1752.8","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780310302"},{"key":"2018112909351367000_42.10.1752.9","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780230202"},{"key":"2018112909351367000_42.10.1752.10","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780380602"},{"key":"2018112909351367000_42.10.1752.11","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780380107"},{"key":"2018112909351367000_42.10.1752.12","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2007.084459"},{"key":"2018112909351367000_42.10.1752.13","unstructured":"Kolodziejczyk K Stappers AE Teleha CA Weerts KJH . 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