{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T19:50:34Z","timestamp":1793994634826,"version":"4.8.0"},"reference-count":39,"publisher":"BMJ","issue":"3","license":[{"start":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T00:00:00Z","timestamp":1755129600000},"content-version":"unspecified","delay-in-days":44,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Novartis Pharma AG"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2025,7,21]]},"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Iscalimab (CFZ533) is a novel, anti-CD40 monoclonal antibody. This study evaluated the efficacy, pharmacokinetics and safety of iscalimab versus placebo as add-on to standard-of-care (SoC) therapy in patients with biopsy-proven active proliferative lupus nephritis (LN).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This was a phase II, randomised, double-blind, placebo-controlled, multicentre study including patients with a diagnosis of systemic lupus erythematosus with active LN. Patients were randomly assigned (2:1) to receive either intravenous iscalimab (10\u2009mg\/kg) or placebo for 24 weeks on top of SoC for LN. The primary efficacy endpoint was the ratio from baseline in urinary protein-to-creatinine ratio (UPCR) at week 24. Safety assessments included adverse events (AEs) and serious AEs (SAEs) during treatment and follow-up up to 49 weeks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Findings<\/jats:title>\n                    <jats:p>Of the 57 patients (iscalimab, n=39; placebo, n=18) randomised, 31 (54.4%) completed the study. The primary efficacy endpoint was met: at week 24, the relative improvement from baseline in proteinuria (UPCR) was 63.1% and 36.3% in the iscalimab and placebo arms, respectively. UPCR to baseline at week 24 showed a statistically significant reduction of 42.1% in the iscalimab versus placebo arm. Most AEs were of mild to moderate severity in both treatment arms. Overall, seven SAEs were reported in six patients (15.4%) in the iscalimab arm versus four in three patients (16.7%) in the placebo arm.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Iscalimab showed a significant improvement in proteinuria (UPCR) in patients with active LN. Iscalimab was generally well tolerated with the exception of a few severe infections and one case of macrophage-activation syndrome in immunosuppressed and comorbid patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT03610516\">NCT03610516<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/rmdopen-2025-005557","type":"journal-article","created":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T10:20:21Z","timestamp":1755166821000},"page":"e005557","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":16,"title":["Efficacy, pharmacokinetics and safety of iscalimab (CFZ533) in patients with proliferative lupus nephritis: a randomised, double-blind, placebo-controlled, phase II study"],"prefix":"10.1136","volume":"11","clinical-trial-number":[{"clinical-trial-number":"nct03610516","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5875-4417","authenticated-orcid":false,"given":"Nan","family":"Shen","sequence":"first","affiliation":[{"name":"Department of Rheumatology, Shanghai JiaoTong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Weinmann-Menke","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Rheumatology and Kidney Transplantation, University Medical Center of the Johannes Gutenberg University, Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Malvar","sequence":"additional","affiliation":[{"name":"Nephrology Unit, Hospital General de Agudos Juan A Fern\u00e1ndez, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7312-0589","authenticated-orcid":false,"given":"Andr\u00e9","family":"Serra-Roma","sequence":"additional","affiliation":[{"name":"Novartis Pharma AG, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Weiss","sequence":"additional","affiliation":[{"name":"Novartis Pharma AG, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1226-9142","authenticated-orcid":false,"given":"Rambabu","family":"Danekula","sequence":"additional","affiliation":[{"name":"Novartis Pharma AG, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carole","family":"Sips","sequence":"additional","affiliation":[{"name":"Novartis Pharma AG, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Rohr","sequence":"additional","affiliation":[{"name":"Novartis Pharma AG, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renaud","family":"Felten","sequence":"additional","affiliation":[{"name":"Novartis Pharma AG, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Gergely","sequence":"additional","affiliation":[{"name":"Novartis Pharma AG, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3865-5435","authenticated-orcid":false,"given":"Tamas","family":"Shisha","sequence":"additional","affiliation":[{"name":"Novartis Pharma AG, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2025,8,14]]},"reference":[{"key":"2025081403201264000_11.3.e005557.1","doi-asserted-by":"crossref","unstructured":"Anders H-J , Ramesh S , Ming-hui Z , et al . 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