OP0124 IMPACT OF GLUCOCORTICOID DOSE THRESHOLD IN DEFINITION OF LUPUS LOW DISEASE ACTIVITY STATE

Background:

The lupus low disease activity state (LLDAS) is a treat-to-target state that has been prospectively validated as protective from organ damage, death, and loss of health-related quality of life for patients with SLE. The 2023 EULAR recommendations for the management of SLE advised a glucocorticoid (GC) dose of no more than 5mg/day [1] whereas the GC threshold in the definition of LLDAS is no more than 7.5mg/day [2].

Objectives:

We sought to determine if lowering the GC ceiling in the definition of LLDAS to 5 mg/day (LLDAS-5) was associated with improved protection from flare, irreversible organ damage accrual and mortality in patients with SLE, compared with the original definition (LLDAS-7.5).

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. Longitudinal associations with mortality were examined using Cox regression, while associations with flare and organ damage accrual were examined using multi-failure multivariate (Prentice, Williams and Peterson-total time (PWP-TT)) models.

Results:

2,213 patients with ≥ 2 years of follow-up data (median 4.9 years [IQR: 3.4, 6.8]) were studied (34,023 visits). 46 patients (2.1%) of the study cohort died; 590 (29%) accrued organ damage, and 1,485 (67%) experienced mild-moderate/severe flares. 1,933 (87%) patients attained LLDAS-7.5 in 15,888 (47%) visits whereas 1,829 (83%) patients attained LLDAS-5 in 14,407 (42%) visits. Most patients in LLDAS-7.5 were also in LLDAS-5 (Figure 1). 104 patients attained LLDAS-7.5 but never attained LLDAS-5.0. The magnitude of protection provided by LLDAS attainment against mortality, irreversible organ damage accrual and flare was similar with both GC thresholds (Table 1). Adjusted hazard ratios (HR) [IQR] of experiencing damage accrual subsequent to spending 12-months in sustained LLDAS-7.5 and LLDAS-5.0 were 0.47 [0.37,0.60, p<0.001], and 0.48 [0.37,0.62, p<0.001] respectively. Likewise, HRs [IQR] of flare and mortality corresponding to 12-months in LLDAS-7.5 and LLDAS-5.0 were similar (Table 1).

Conclusion:

Lowering GC dose remains a key goal of management in SLE, but no evidence was adduced to support revising the GC dose threshold of the LLDAS definition. The validated LLDAS definition should continue to be used in studies and patient care.

REFERENCES:

[1] Fanouriakis A, Kostopoulou M, Andersen J, Aringer M, Arnaud L, Bae SC, et al. EULAR recommendations for the management of systemic lupus erythematosus: 2023 update. Annals of the rheumatic diseases. 2023 Oct 12. [2] 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. Table 1. Comparison of longitudinal associations of LLDAS definitions with different glucocorticoid thresholds (PNL ≤7.5 vs PNL≤5.0) Hazard ratios adjusted for ¹age and national gross domestic product (GDP); ²age, GDP and baseline organ damage, and ³GDP and SDI score. t-1 = at preceding visit

Acknowledgements:

We acknowledge the Asia Pacific Lupus Collaboration (APLC) patient cohort participants and the data collectors at all APLC sites.

Disclosure of Interests:

Rangi Kandane-Rathnayake GSK, Novartis (all institutional research grants), Vera Golder: None declared, Alberta Hoi On the advisory board for Abbvie and GSK, AstraZeneca, GSK, BMS, Janssen, and Merck Serono, 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 Astra-Zeneca, Boehringer Ingelheim, Glaxo Smith Kline, Pfizer, Astra Zeneca, Biogen, Boehringer Ingelheim, Aurinia, Biogen, Idorsia, Novartis, Leonid Zamora: None declared, Zhanguo Li: None declared, Sargunan Sockalingam: None declared, Yasuhiro Katsumata Asahi Kasei Pharma, Astellas Pharma Inc., AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd., GlaxoSmithKline K.K., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Corporation, Pfizer Japan Inc., Sanofi K.K., Masayoshi Harigai MH has received speaker's fee from 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., AbbVie, Boehringer-ingelheim, Bristol Myers Squibb Co., Kissei Pharmaceutical Co.,Ltd. and Teijin Pharma., 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, Duminda Basnayake: None declared, Madelynn Chan: None declared, Jun Kikuchi: None declared, Tsutomu Takeuchi Bristol-Myers Squibb, Eli Lilly Japan, Mitsubishi-Tanabe Pharma Corp., Sanofi K.K., Eli Lilly Japan, Astellas Pharma, Inc., Mitsubishi-Tanabe Pharma Corp., Shionogi & Co., Ltd, Shereen Oon: None declared, Sang-Cheol Bae: None declared, Sean O'Neill: None declared, Fiona Goldblatt: None declared, Kristine Pek Ling Ng: None declared, Annie Law Hui Nee: None declared, Nicola Tugnet: None declared, Sunil Kumar: None declared, Cherica Tee: None declared, Michael Tee: None declared, Naoaki Ohkubo: None declared, Yoshiya Tanaka Eli Lilly, AstraZeneca, Abbvie, Gilead, Chugai, Behringer-Ingelheim, GlaxoSmithKline, Eisai, Taisho, Bristol-Myers, Pfizer, Taiho, Mitsubishi-Tanabe, Eisai, Chugai, Taisho, Chak Sing Lau: None declared, Mandana Nikpour AstraZeneca, Boehringer Ingelheim, GSK, Janssen, AstraZeneca, Boehringer Ingelheim, GSK, Janssen, Boehringer Ingelheim, Janssen, Eric Morand AstraZeneca, Merck, Gilead, Roche, EMD Serono, AstraZeneca, Biogen, Bristol Myers Squibb, Eli Lilly, Genentech, GlaxoSmithKline, Janssen, Novartis, AbbVie, Galapagos, IgM, AbbVie, Amgen, AstraZeneca, Biogen, BMS, Eli Lilly, EMD Serono, Genetech, GSK, Janssen, UCB (all institutional).