ATTAINMENT OF LUPUS LOW DISEASE ACTIVITY STATE EXCLUSIVE OF REMISSION IS PROTECTIVE AGAINST ADVERSE OUTCOMES IN SYSTEMIC LUPUS ERYTHEMATOSUS

R. Kandane-Rathnayake, V. Golder, W. Louthrenoo, Y. H. Chen, J. Cho, A. Lateef, L. Hamijoyo, S. F. Luo, Y. J. Jan Wu, S. Navarra, L. Zamora, Z. LI, S. Sockalingam, Y. Katsumata, M. Harigai, Y. Hao, Z. Zhang, B. Basnayake, M. Chan, J. Kikuchi, T. Takeuchi, S. Oon, S. C. Bae, S. O’neill, F. Goldblatt, K. Ng, A. Law, N. Tugnet, S. Kumar, M. Tee, C. Tee, Y. Tanaka, C. S. Lau, M. Nikpour, A. Hoi, E. F. MorandMonash University Clayton Campus, Medicine, Clayton, Australia Chiang Mai University Hospital, Department of Internal Medicine, Faculty of Medicine, Chiang Mai, Thailand Taichung Veterans General Hospital, Division of Allergy, Immunology and Rheumatology, Taichung, Taiwan, Republic of China National University Hospital, Rheumatology, Singapore, Singapore Padjadjaran University/ Hasan Sadikin General Hospital, Internal Medicine, Bandung, Indonesia Chang Gung Memorial Hospital, Rheumatology, Allergy and Immunology, Taipei, Taiwan, Republic of China University of Santo Tomas Hospital, Joint and Bone Center, Manila, Philippines Peking University First Hospital, Rheumatology and Immunology department, Beijing, China University of Malaya, Medicine, Kuala Lumpur, Malaysia Tokyo Women’s Medical University, Rheumatology, Tokyo, Japan Peking University First Hospital, Rheumatology and Immunology, Beijing, China St Vincent’s Hospital Melbourne, Rheumatology, Fitzroy, Australia Teaching Hospital Kandy, Division of Nephrology, Kandy, Sri Lanka Tan Tock Seng Hospital, Rheumatology, Allergy & Immunology, Tan Tock Seng, Singapore Keio University, Internal Medicine, Tokyo, Japan Hanyang University Hospital for Rheumatic Diseases, Rheumatology, Seoul, Korea, Rep. of (South Korea) Liverpool Hospital, Rheumatology, Liverpool, Australia UNSW Sydney, Rheumatology, Sydney, Australia Flinders Medical Centre, Rheumatology, Bedford Park, Australia Royal Adelaide Hospital, Rheumatology, North Terrace, Australia North Shore Hospital, Medicine, Auckland, New Zealand Singapore General Hospital, Medicine, Singapore, Singapore Greenlane Clinical Centre, Rheumatology, Auckland, New Zealand Middlemore Hospital, Rheumatology, Auckland, New Zealand University of the Philippines Manila, Internal Medicine and Rheumatology, Manila, Philippines University of Occupational and Environmental Health, Internal Medicine, Kitakyushu, Japan the University of Hong Kong, Medicine, Pok Fu Lam, Hong Kong (SAR)  Background The lupus low disease activity state (LLDAS) treat-to-target definition sets a ceiling for acceptable disease and treatment burden in SLE. Definition of Remission in SLE (DORIS) is a more stringent state, but as it is concentric with LLDAS many patients in LLDAS also meet the DORIS remission definition. Studies in cohorts with a majority of patients in remission poorly separate LLDAS and remission, leading to debate about the independent effects of LLDAS on SLE outcomes. Objectives We examined whether being in LLDAS but not remission provided protection against adverse outcomes of flare, irreversible organ damage accrual and mortality in patients with SLE. Methods Data from a 13-country longitudinal SLE cohort (ACR/SLICC criteria), collected prospectively between 2013 and 2020, were analysed. Organ damage and flare were captured using SLICC Damage Index and SELENA-SLEDAI Flare Index, respectively. LLDAS was defined as Golder et al., 2019 [1] (SLEDAI<4, no new activity, PGA <1, prednisolone (PNL) <7.5 mg/d, antimalarials (AM) and immunosuppressants (IS) allowed). Remission was defined as Vollenhoven et al, 2021 [2] (clinical SLEDAI=0, PGA <0.5, PNL<5 mg/d, AM/IS allowed). Results 3,811 patients with ≥ 2 visits followed over a median of 2.8 years [IQR: 1.0 to 5.3] were studied. 80 (2.1%) patients died; 717 (21%) accrued organ damage, and 2,142 (56%) experienced mild-moderate or severe flare during the study period. 55% (n=2,099) attained LLDAS but not remission (LLDAS+REM-) at least once, with a median (IQR) cumulative percent-time spent in LLDAS+REM- of 21.5% [9.8, 42.9]. Overall, 63% attained both LLDAS and remission (LLDAS+REM+) with median (IQR) cumulative time 45% [22, 71]; 18% attained LLDAS+REM-., and 19% of patients never attained LLDAS or REM. Compared to patients who never attained LLDAS or remission (LLDAS-REM-), LLDAS+REM- attainment at any time during the study observation period provided significant protection against subsequent flare and damage accrual, and protection against mortality with borderline statistical significance, after adjusting for potential confounding factors (Table 1). Similarly, ≥50% of cumulative observed time in LLDAS+REM- provided significant protection against flare and damage accrual but not mortality, possibly due to lack of power (Table 1). Protective effects of LLDAS+REM+ were also confirmed. Table 1. Longitudinal associations of LLDAS+REM- attainment with flare, organ damage accrual and mortality Flaret Damage accrualt Mortalityt HR (95%CI) p-value HR (95%CI) p-value HR (95%CI) p-value Not in LLDAS or REMt-1 1.00 1.00 1.00 LLDAS+REM-t-1 0.66 (0.60, 073)p<0.0001 0.63 (0.52, 0.77)p<0.0001 0.14 (0.02, 1.07)p=0.059 LLDAS+REM+t-1 0.57 (0.52, 0.61)p<0.0001 0.46 (0.39, 0.54)p<0.0001 0.22 (0.08, 0.65)P=0.006 <50%T in LLDAS+REM- t-1 1.00 1.00 1.00 ≥50%T in LLDAS+REM- t-1 0.71 (0.62, 0.81)p<0.0001 0.72 (0.56, 0.92)p=0.010 0.39 (0.14, 1.10)p=0.08 <50%T in LLDAS+REM+ t-1 1.00 1.00 1.00 ≥50%T in LLDAS+REM+ t-1 0.62 (0.56, 0.67)P<0.0001 0.64 (0.53, 0.76)P<0.0001 0.53 (0.19, 1.43)p=0.21 Hazard ratios adjusted for age and national gross domestic product (GDP); age, GDP and baseline organ damage, and GDP and SDI score. T=time. Conclusion Attainment of LLDAS provides significant protection against flare and organ damage accrual even when excluding patients who are also meet the definition of remission. LLDAS is an independent predictor of improved outcomes in SLE. References Golder V, Kandane-Rathnayake R, Huq M, Nim H, Louthrenoo W, Luo SF, et al. Lupus low disease activity state as a treatment endpoint for systemic lupus erythematosus: a prospective validation study. The Lancet Rheumatology. 2019; 1(2):e95–e102. van Vollenhoven RF, Bertsias G, Doria A, Isenberg D, Morand E, Petri MA, et al. 2021 DORIS definition of remission in SLE: final recommendations from an international task force. Lupus science & medicine. 2021 Nov; 8[1]. Acknowledgements 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. Disclosure of Interests 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: Jannsen, 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, BMDB Basnayake: 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, Sean O’Neill: None declared, Fiona Goldblatt: None declared, Kristine Ng Consultant of: AbbVie, Annie Law: None declared, Nicola Tugnet: None declared, Sunil Kumar: None declared, Michael Tee: None declared, Cherica 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: 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. Keywords: Systemic lupus erythematosus, Real-world evidence, Treat to target DOI: 10.1136/annrheumdis-2023-eular.2440Citation: , volume 82, supplement 1, year 2023, page 149Session: Updates on management and outcomes in SLE and Sjogren syndrome (Oral Presentations)