POS1481 INFORMING TRIAL MEASUREMENT IN SYSTEMIC LUPUS ERYTHEMATOSUS: FREQUENCY OF DOMAIN-SPECIFIC DISEASE ACTIVITY IN A MULTI-NATIONAL OBSERVATIONAL COHORT
Authors: K. Connelly; R. Kandane‐Rathnayake; V. Golder; W. Louthrenoo; Y. H. Chen; J. Cho; A. Lateef; L. Hamijoyo; S. Luo; Y. Jan Wu; S. Navarra; L. Zamora; Z. Li; S. Sockalingam; Y. Katsumata; M. Harigai; Y. Hao; Z. Zhang; M. Chan; J. Kikuchi; T. Takeuchi; S. Oon; S. Bae; F. Goldblatt; S. O’Neill; K. Ng; A. Law; B. Basnayake; N. Tugnet; S. Kumar; C. Tee; M. Tee; Y. Tanaka; C. Lau; M. Nikpour; A. Hoi; E. Morand
Year: 2023

Systemic lupus erythematosus (SLE) has heterogeneous organ manifestations that occur in different combinations at an individual patient level. Current SLE clinical trial eligibility criteria and efficacy endpoints, based on legacy disease activity measures, have multiple weaknesses. Understanding the frequency with which different organ manifestations are represented in contemporary SLE cohorts is required, to allow focus on the most frequent and impactful manifestations of disease in both eligibility criteria and endpoints.To report the prevalence of disease activity in individual organ domains in SLE patients, both overall and in patients meeting the most common disease activity cut-off for clinical trial eligibility (SLEDAI2K ≥6).We used data from a multinational SLE cohort, prospectively collected between 2013 and 2020. We analysed data from 4,102 patients with criteria-defined SLE, who contributed 42,345 visits with complete SLEDAI-2K assessments. Disease activity assessed using SLEDAI-2K was categorised according to activity in 9 organ systems: central nervous system (CNS), vasculitis, musculoskeletal, renal, cutaneous, serositis, serological, haematological, and fever. Proportions of organ-specific disease activity in the overall cohort, and stratified by total SLEDAI-2K ≥6 or <6, were calculated.In the overall cohort, 3,659 patients (89.2%) had SLEDAI-2K >0 on at least one visit (31,290 visits, 73.9%). Serological disease activity was the most prevalent in the cohort overall, affecting 75.5% of patients at least once, followed by renal (41.6%), cutaneous (36.5%), musculoskeletal (20%) and haematological (19%) activity. Infrequent active manifestations affecting <5% of patients were serositis (3.4%), vasculitis (3.4%), CNS (3.0%) and fever (3%).We further examined the prevalence of domain-specific disease activity in patient visits stratified by a SLEDAI-2K cut-off of 6 (Table 1). In patient visits with a SLEDAI-2K>6 (n = 10,031 visits, 24% of total) the most common manifestations were serological (90%) and renal (73%), followed by cutaneous (26%) and musculoskeletal (14%). Conversely, 7.3% of visits with renal, 6.7% with cutaneous, 5.8% with haematological and 1.3% with musculoskeletal activity did not have a SLEDAI-2K ≥6 (Table 1).Table 1.Frequencies and percentages of patient visits with specific organ system disease activity, stratified by total SLEDAI score cut-off of ≥6 vs <6.All visitsSLEDAI<6SLEDAI≥6n = 42,345n = 32,314n =10,031p-value*Serological25,745 (60.8%)16,740 (51.8%)9,005 (89.8%)<0.001Renal9,684 (22.9%)2,367 (7.3%)7,317 (72.9%)<0.001Cutaneous4,806 (11.3%)2,158 (6.7%)2,648 (26.4%)<0.001Haematological2,615 (6.2%)1,862 (5.8%)753 (7.5%)<0.001Musculoskeletal1,856 (4.4%)422 (1.3%)1,434 (14.3%)<0.001Serositis255 (0.6%)81 (0.3%)174 (1.7%)<0.001Vasculitis250 (0.6%)0250 (2.5%)<0.001CNS200 (0.5%)0200 (2.0%)<0.001Fever149 (0.4%)59 (0.2%)90 (0.9%)<0.001*P-values derived from Pearson’s Chi-Squared tests.Serological, renal, cutaneous, musculoskeletal and haematological manifestations predominate in patients with active SLE in our cohort, with other organs only rarely affected. Measures of improvement in SLE trial endpoints could focus on measuring change in these systems, and omit detailed analysis of rare events. Conversely, a notable proportion of patients with active disease in commonly affected organ domains had SLEDAI-2K <6, meaning they would be excluded from clinical trials. Incorporation of organ-specific activity measures and inclusion criteria for SLE clinical trials may overcome this limitation and improve recruitment to and results of trials.We acknowledge the unrestricted project grants received from AstraZeneca, BMS, Eli Lilly, GSK, Janssen, Merck Serono, and UCB to support data collection and project management contributing to this work.Kathryn Connelly: None declared, Rangi Kandane-Rathnayake: None declared, Vera Golder: None declared, Worawit Louthrenoo: None declared, Yi-Hsing Chen: None declared, Jiacai Cho: None declared, Aisha Lateef: None declared, Laniyati Hamijoyo: None declared, Shue Fen Luo: None declared, Yeong-Jian Jan Wu: None declared, Sandra Navarra Consultant of: Biogen, Boehringer Ingelheim, Astra Zeneca, Grant/research support from: Janssen, Novartis, Pfizer, Glaxo Smith Kline, Pfizer, Leonid Zamora: None declared, Zhanguo Li Consultant of: Pfizer, Roche, Janssen, Abbott, AbbVie, Bristol Myers Squibb, MSD, Celgene, Eli Lilly, GSK, Novartis, UCB Pharma, Grant/research support from: Pfizer, Roche, Janssen, Abbott, AbbVie, Bristol Myers Squibb, MSD, Celgene, Eli Lilly, GSK, Novartis, UCB Pharma, Sargunan Sockalingam Consultant of: Pfizer, AstraZeneca, ZP Therapeutics, Grant/research support from: Pfizer, AstraZeneca, ZP Therapeutics, Yasuhiro Katsumata Grant/research support from: GlaxoSmithKline K.K. AstraZeneca K.K. Sanofi K.K. Pfizer Japan Inc., Janssen Pharmaceutical K.K., Chugai Pharmaceutical Co., Ltd., Asahi Kasei Pharma, Astellas Pharma Inc., Mitsubishi Tanabe Pharma Corporation, Masayoshi Harigai Speakers bureau: AbbVie Japan GK, Ayumi Pharmaceutical Co., Boehringer Ingelheim Japan, Inc.,Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., GlaxoSmithKline K.K., Kissei Pharmaceutical Co., Ltd., Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd., and Teijin Pharma Ltd, Consultant of: AbbVie, Boehringer-ingelheim, Bristol Myers Squibb Co., Kissei Pharmaceutical Co.,Ltd. and Teijin Pharma, Grant/research support from: AbbVie Japan GK, Asahi Kasei Corp., Astellas Pharma Inc., Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Daiichi-Sankyo, Inc.,Eisai Co., Ltd., Kissei Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Nippon Kayaku Co., Ltd., Sekiui Medical, Shionogi & Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and Teijin Pharma Ltd., Yanjie Hao: None declared, Zhuoli Zhang: None declared, Madelynn Chan: None declared, Jun Kikuchi: None declared, Tsutomu Takeuchi Consultant of: AbbVie, Chugai, Mitsubishi-Tanabe, Grant/research support from: AbbVie, Mitsubishi-Tanabe, Eli Lilly Japan, Shereen Oon: None declared, Sang-Cheol Bae: None declared, Fiona Goldblatt: None declared, Sean O’Neill: None declared, Kristine Ng Consultant of: AbbVie, Annie Law: None declared, BMDB Basnayake: None declared, Nicola Tugnet: None declared, Sunil Kumar: None declared, Cherica Tee: None declared, Michael Tee: None declared, Yoshiya Tanaka Speakers bureau: Behringer-Ingelheim, Eli Lilly, Abbvie, Gilead, AstraZeneca, Bristol-Myers, Chugai, Daiichi-Sankyo, Eisai, Pfizer, Mitsubishi-Tanabe, GlaxoSmithKline, Grant/research support from: Asahi-Kasei, Abbvie, Chugai, Eisai, Takeda, Daiichi-Sankyo, Behringer-Ingelheim, C.S. Lau Speakers bureau: AstraZeneca UK Ltd, Consultant of: AstraZeneca Pharmaceuticals LP, Mandana Nikpour Speakers bureau: Actelion, GSK, Janssen, Pfizer, UCB, Paid instructor for: UCB, Consultant of: Actelion, Boehringer Ingelheim, Certa Therapeutics, Eli Lilly, GSK, Janssen, Pfizer, UCB, Grant/research support from: Actelion, Astra Zeneca, BMS, GSK, Janssen, UCB, Alberta Hoi Speakers bureau: UCB, Janssen, Sandoz, Eli Lilly, Consultant of: AbbVie, GSK, Grant/research support from: AstraZeneca, GSK, BMS, Janssen, and Merck Serono, Eric F. Morand Speakers bureau: AstraZeneca, EMD Serono, Gilead, Consultant of: AstraZeneca, BristolMyersSquibb, Biogen, Eli Lilly, EMD Serono, Novartis, Grant/research support from: AbbVie, Amgen, AstraZeneca, BristolMyersSquibb, Biogen, Eli Lilly, EMD Serono, Genentech, GSK, Janssen, UCB.