{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T16:34:42Z","timestamp":1792859682569,"version":"4.5.0"},"reference-count":36,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2012,4,26]],"date-time":"2012-04-26T00:00:00Z","timestamp":1335398400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2012,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To assess the efficacy of paquinimod, a new immunomodulatory small molecule, in a murine lupus model, and to evaluate its pharmacokinetics and tolerability in systemic lupus erythematosus (SLE) patients at doses predicted to be efficacious and safe and determine the maximum tolerated dose.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The efficacy of paquinimod was studied in lupus\u2010prone MRL\u2010\n                      <jats:italic>lpr\/lpr<\/jats:italic>\n                      mice and compared with that of established SLE treatments. Dose\u2010response data and pharmacokinetic data were used to calculate effective and safe clinical doses of paquinimod. The pharmacokinetics and tolerability of paquinimod were evaluated in a phase Ib double\u2010blind, placebo controlled, dose\u2010ranging study in which cohorts of SLE patients received daily oral treatment for 12 weeks.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Paquinimod treatment resulted in disease inhibition in MRL\u2010\n                      <jats:italic>lpr\/lpr<\/jats:italic>\n                      mice, comparable to that obtained with prednisolone and mycophenolate mofetil; prominent effects on disease manifestations and serologic markers and a steroid\u2010sparing effect were observed. In patients with SLE, the pharmacokinetic properties of paquinimod were linear and well suitable for once\u2010daily oral treatment. The majority of the adverse events (AEs) were mild or moderate, and transient. The most frequent AEs were arthralgia and myalgia, reported with the highest dose levels of paquinimod (4.5 mg\/day and 6.0 mg\/day). At the 4.5 mg\/day dose level and higher, some AEs of severe intensity and serious adverse events were reported.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Paquinimod effectively inhibited disease and had a steroid\u2010sparing effect in experimental lupus. Results from preclinical models together with pharmacokinetic data were successfully translated into a safe clinical dose range, and doses of up to 3.0 mg\/day were well tolerated in the SLE patients. Taken together, the promising combined data from a murine model and human SLE support the future clinical development of paquinimod.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.33493","type":"journal-article","created":{"date-parts":[[2011,12,1]],"date-time":"2011-12-01T18:35:15Z","timestamp":1322764515000},"page":"1579-1588","source":"Crossref","is-referenced-by-count":121,"title":["Pharmacokinetics, tolerability, and preliminary efficacy of paquinimod (ABR\u2010215757), a new quinoline\u20103\u2010carboxamide derivative: Studies in lupus\u2010prone mice and a multicenter, randomized, double\u2010blind, placebo\u2010controlled, repeat\u2010dose, dose\u2010ranging study in patients with systemic lupus erythematosus"],"prefix":"10.1002","volume":"64","author":[{"given":"Anders A.","family":"Bengtsson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunnar","family":"Sturfelt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Lood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"R\u00f6nnblom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald F.","family":"van Vollenhoven","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bengt","family":"Axelsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgitta","family":"Sparre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hel\u00e9n","family":"Tuvesson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie Wall\u00e9n","family":"\u00d6hman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomas","family":"Leanderson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,4,26]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra071297"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm031044w"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01972810"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00399792"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1567-5769(01)00041-8"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(02)00225-4"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2005.11.023"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s001250051028"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.47.4.895"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.47.2.341"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.54.9.1726"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.54.9.1734"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1177\/135245850000600208"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1099-081X(199910)20:7<347::AID-BDD194>3.0.CO;2-0"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/1099-081X(200003)21:2<53::AID-BDD214>3.0.CO;2-F"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000154520.48391.69"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)60918-6"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.2217\/14796708.3.6.641"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar3314"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1000097"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2004.07.009"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780251101"},{"key":"e_1_2_7_24_2","first-page":"288","article-title":"Systemic lupus erythematosus disease activity index 2000","volume":"29","author":"Gladman DD","year":"2002","journal-title":"J Rheumatol"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.21890"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2776(08)60342-9"},{"key":"e_1_2_7_27_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2007.070367"},{"key":"e_1_2_7_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/39.1.18"},{"key":"e_1_2_7_29_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01965044"},{"key":"e_1_2_7_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/0923-2494(89)90117-X"},{"key":"e_1_2_7_31_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780291115"},{"key":"e_1_2_7_32_2","first-page":"589","article-title":"Effects of LS\u20102616 administration upon the autoimmune disease of (NZB \u00d7 NZW) F1 hybrid mice","volume":"59","author":"Tarkowski A","year":"1986","journal-title":"Immunology"},{"key":"e_1_2_7_33_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar625"},{"key":"e_1_2_7_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.21571"},{"key":"e_1_2_7_35_2","doi-asserted-by":"publisher","DOI":"10.1191\/096120300674499064"},{"key":"e_1_2_7_36_2","doi-asserted-by":"publisher","DOI":"10.1080\/08916930310001625952"},{"key":"e_1_2_7_37_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-03-274605"}],"container-title":["Arthritis &amp; Rheumatism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.33493","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.33493","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T21:55:16Z","timestamp":1698702916000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/art.33493"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,4,26]]},"references-count":36,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2012,5]]}},"alternative-id":["10.1002\/art.33493"],"URL":"https:\/\/doi.org\/10.1002\/art.33493","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.714897805.790252957","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.714897805.791652962","asserted-by":"object"}]},"ISSN":["0004-3591","1529-0131"],"issn-type":[{"value":"0004-3591","type":"print"},{"value":"1529-0131","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,4,26]]}}}