{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T22:52:01Z","timestamp":1793659921044,"version":"4.5.1"},"reference-count":51,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T00:00:00Z","timestamp":1758153600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005614","name":"Biogen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005614","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis & Rheumatology"],"published-print":{"date-parts":[[2025,12]]},"abstract":"\n Objective<\/jats:title>\n The pharmacodynamic effects of litifilimab on type I interferon (IFN) response and correlations with clinical outcomes were investigated in systemic lupus erythematosus (SLE) and cutaneous lupus erythematosus (CLE).<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Participants from part A (SLE) or part B (CLE with or without SLE) of the randomized phase 2 LILAC trial who received litifilimab (at 50 mg, 150 mg, or 450 mg) or a placebo were included. IFN gene signature (IFNGS) scores were assessed from whole\u2010blood samples using a 22\u2010gene panel in 120 and 131 participants (parts A and B, respectively). IFN\u03b1 and other IFN\u2010regulated cytokine concentrations were measured in serum in 112 and 131 participants (parts A and B, respectively).<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Most participants were IFNGS\u2010high at baseline (79\u201391%), and no baseline IFNGS\u2010low participant results were reported. In IFNGS\u2010high participants, litifilimab induced rapid, significant (nominal\n P<\/jats:italic>\n < 0.05), and sustained reductions in IFNGS scores and IFN\u03b1 concentrations versus a placebo for litifilimab at 450 mg in part A and for litifilimab at 150 mg and 450 mg in part B. In part A, IFN\u03b1 reductions with litifilimab were correlated with clinical response measures. In part B, dose\u2010response relationships for IFNGS score and IFN\u03b1 concentration were observed, similar to those for disease activity measured with the Cutaneous Lupus Erythematosus Disease Area and Severity Index\u2013Activity (CLASI\u2010A) score.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n Administration of litifilimab resulted in reductions in both IFNGS scores and IFN\u03b1 concentrations, pharmacodynamic effects that correlated with clinical responses. These findings support the mechanism of action of litifilimab and its continued evaluation in larger studies of patients with SLE or CLE.<\/jats:p>\n \n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/art.43271","type":"journal-article","created":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T06:54:34Z","timestamp":1749452074000},"page":"1726-1738","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Pharmacodynamic Effects of Litifilimab in Lupus in a Randomized, Placebo\u2010Controlled Phase 2 Study: Rapid and Sustained Reductions in Type I Interferon\u2010Associated Gene Expression and Cytokines"],"prefix":"10.1002","volume":"77","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6712-1585","authenticated-orcid":false,"given":"Richard","family":"Furie","sequence":"first","affiliation":[{"name":"Northwell Health Great Neck New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria P.","family":"Werth","sequence":"additional","affiliation":[{"name":"University of Pennsylvania and Corporal Michael J. 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