{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T16:32:37Z","timestamp":1791995557871,"version":"4.4.0"},"reference-count":49,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,11,29]],"date-time":"2022-11-29T00:00:00Z","timestamp":1669680000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CPT Pharmacom &amp; Syst Pharma"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Systemic lupus erythematosus (SLE) is an autoimmune disease affecting multiple organ systems. Many investigational agents have failed or shown only modest effects when added to standard of care (SoC) therapy in placebo\u2010controlled trials, and only two therapies have been approved for SLE in the last 60\u2009years. Clinical trial outcomes have shown discordance in drug effects between clinical endpoints. Herein, we characterized longitudinal disease activity in the SLE population and the sources of variability by developing a latent disease trajectory model for SLE component endpoints (Systemic Lupus Erythematosus Disease Activity Index [SLEDAI], Physician's Global Assessment [PGA], British Isles Lupus Assessment Group Index [BILAG]) and composite endpoints (Systemic Lupus Erythematosus Responder Index [SRI], BILAG\u2010based Composite Lupus Assessment [BICLA], and Lupus Low Disease Activity State [LLDAS]) using patient\u2010level historical SoC data from nine phase II and III studies. Across all endpoints, in predictions up to 52\u2009weeks from the final disease trajectory model, the following baseline covariates were associated with a greater decrease in SLE disease activity and higher response to placebo\u2009+\u2009SoC: Hispanic ethnicity from Central\/South America, absence of hypocomplementemia, recent SLE diagnosis, and high baseline disease activity score using SLEDAI and BILAG separately. No discernible differences were observed in the trajectory of response to placebo\u2009+\u2009SoC across different SoC medications (antimalarial and immunosuppressant such as mycophenolate, methotrexate, and azathioprine). Across all endpoints, disease trajectory showed no difference in Asian versus non\u2010Asian patients, supporting Asia\u2010inclusive global SLE drug development. These results describe the first population approach to support a model\u2010informed drug development framework in SLE.<\/jats:p>","DOI":"10.1002\/psp4.12888","type":"journal-article","created":{"date-parts":[[2022,11,9]],"date-time":"2022-11-09T10:53:32Z","timestamp":1667991212000},"page":"180-195","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Disease trajectory of\n                    <scp>SLE<\/scp>\n                    clinical endpoints and covariates affecting disease severity and probability of response: Analysis of pooled\n                    <scp>patient\u2010level<\/scp>\n                    placebo (\n                    <scp>Standard\u2010of\u2010Care<\/scp>\n                    ) data to enable\n                    <scp>model\u2010informed<\/scp>\n                    drug development"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8971-8283","authenticated-orcid":false,"given":"Kosalaram","family":"Goteti","sequence":"first","affiliation":[{"name":"EMD Serono Research and Development Institute, Inc (an affiliate of Merck KGaA, Darmstadt Germany)  Billerica Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9649-169X","authenticated-orcid":false,"given":"Jonathan","family":"French","sequence":"additional","affiliation":[{"name":"Metrum Research Group  Tariffville Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramon","family":"Garcia","sequence":"additional","affiliation":[{"name":"Metrum Research Group  Tariffville Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Li","sequence":"additional","affiliation":[{"name":"EMD Serono Research and Development Institute, Inc (an affiliate of Merck KGaA, Darmstadt Germany)  Billerica Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Casset\u2010Semanaz","sequence":"additional","affiliation":[{"name":"EMD Serono Research and Development Institute, Inc (an affiliate of Merck KGaA, Darmstadt Germany)  Billerica Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aida","family":"Aydemir","sequence":"additional","affiliation":[{"name":"EMD Serono Research and Development Institute, Inc (an affiliate of Merck KGaA, Darmstadt Germany)  Billerica Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Townsend","sequence":"additional","affiliation":[{"name":"EMD Serono Research and Development Institute, Inc (an affiliate of Merck KGaA, Darmstadt Germany)  Billerica Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina Vazquez","family":"Mateo","sequence":"additional","affiliation":[{"name":"EMD Serono Research and Development Institute, Inc (an affiliate of Merck KGaA, Darmstadt Germany)  Billerica Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Studham","sequence":"additional","affiliation":[{"name":"EMD Serono Research and Development Institute, Inc (an affiliate of Merck KGaA, Darmstadt Germany)  Billerica Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Guenther","sequence":"additional","affiliation":[{"name":"Merck KGaA  Darmstadt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Kao","sequence":"additional","affiliation":[{"name":"EMD Serono Research and Development Institute, Inc (an affiliate of Merck KGaA, Darmstadt Germany)  Billerica Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5725-5835","authenticated-orcid":false,"given":"Marc","family":"Gastonguay","sequence":"additional","affiliation":[{"name":"Metrum Research Group  Tariffville Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Girard","sequence":"additional","affiliation":[{"name":"Merck Institute of Pharmacometrics  Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Benincosa","sequence":"additional","affiliation":[{"name":"EMD Serono Research and Development Institute, Inc (an affiliate of Merck KGaA, Darmstadt Germany)  Billerica Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4039-9813","authenticated-orcid":false,"given":"Karthik","family":"Venkatakrishnan","sequence":"additional","affiliation":[{"name":"EMD Serono Research and Development Institute, Inc (an affiliate of Merck KGaA, Darmstadt Germany)  Billerica Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,11,29]]},"reference":[{"issue":"11","key":"e_1_2_10_2_1","first-page":"S37","article-title":"Measures of adult systemic lupus erythematosus: updated version of British Isles lupus assessment group (BILAG 2004), European consensus lupus activity measurements (ECLAM), systemic lupus activity measure, revised (SLAM\u2010R), systemic lupus activity questionnaire for population studies (SLAQ), systemic lupus erythematosus disease activity index 2000 (SLEDAI\u20102K), and systemic lupus international collaborating clinics\/American College of Rheumatology Damage Index (SDI)","volume":"63","author":"Romero\u2010Diaz J","year":"2011","journal-title":"Arthritis Care 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