OP0226 ATTAINMENT OF LUPUS LOW DISEASE ACTIVITY STATE EXCLUSIVE OF REMISSION IS PROTECTIVE AGAINST ADVERSE OUTCOMES IN SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: 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; B. Basnayake; M. Chan; J. Kikuchi; T. Takeuchi; S. Oon; S. Bae; S. O’Neill; F. Goldblatt; K. Ng; A. Law; N. Tugnet; S. Kumar; M. Tee; C. Tee; Y. Tanaka; C. Lau; M. Nikpour; A. Hoi; E. Morand
Year: 2023

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.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.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 Golderet 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 Vollenhovenet al, 2021 [2] (clinical SLEDAI=0, PGA <0.5, PNL<5 mg/d, AM/IS allowed).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 mortalityFlaretDamage accrualtMortalitytHR1(95%CI)p-valueHR2(95%CI)p-valueHR3(95%CI)p-valueNot in LLDAS or REMt-11.001.001.00LLDAS+REM-t-10.66 (0.60, 073)p<0.00010.63 (0.52, 0.77)p<0.00010.14 (0.02, 1.07)p=0.059LLDAS+REM+t-10.57 (0.52, 0.61)p<0.00010.46 (0.39, 0.54)p<0.00010.22 (0.08, 0.65)P=0.006<50%T in LLDAS+REM-t-11.001.001.00≥50%T in LLDAS+REM-t-10.71 (0.62, 0.81)p<0.00010.72 (0.56, 0.92)p=0.0100.39 (0.14, 1.10)p=0.08<50%T in LLDAS+REM+t-11.001.001.00≥50%T in LLDAS+REM+t-10.62 (0.56, 0.67)P<0.00010.64 (0.53, 0.76)P<0.00010.53 (0.19, 1.43)p=0.21Hazard ratios adjusted for1age and national gross domestic product (GDP);2age, GDP and baseline organ damage, and3GDP and SDI score. T=time.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.[1]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.[2]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].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.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.