Lupus Low Disease Activity State Attainment Provides Significant Protection Against Mortality: A Multi-National, Longitudinal Observational Study

Rangi Kandane-Rathnayake¹, Vera Golder¹, Worawit Louthrenoo², YI-HSING CHEN³, Jiacai Cho⁴, Aisha Lateef⁵, Laniyati Hamijoyo⁶, Shue-Fen Luo⁷, Yeong-Jian Wu⁸, Sandra Navarra⁹, Leonid Zamora⁹, Zhanguo Li¹⁰, Yuan An¹⁰, Sargunan Sockalingam¹¹, Yasuhiro Katsumata¹², Masayoshi Harigai¹², Yanjie Hao¹³, Zhuoli Zhang¹³, B.M.D.B. Basnayake¹⁴, Madelynn Chan¹⁵, Jun Kikuchi¹⁶, Tsutomu Takeuchi¹⁷, Shereen Oon¹⁸, Sang-Cheol Bae¹⁹, Sean O’Neill²⁰, Fiona Goldblatt²¹, Kathryn Gibson²⁰, Kristine (Pek Ling) Ng²², Annie Law²³, Nicola Tugnet²⁴, Sunil Kumar²⁵, Michael Tee²⁶, DaeYoung Yu²⁷, Chetan Karyekar²⁸, Yoshiya Tanaka²⁹, C.S. Lau³⁰, Mandana Nikpour³¹, Alberta Hoi³² and Eric Morand³³, ¹Monash University, Clayton, Australia, ²Maharaj Nakorn Chiangmai, Chiang Mai, Thailand, ³Taichung Veterans General Hospital, Taichung, Taiwan (Republic of China), ⁴National University Health System (NUHS), Singapore, Singapore, ⁵National University Hospital, Singapore, Singapore, ⁶University of Padjadjaran, Bandung, Indonesia, ⁷Chang Gung Memorial Hospital, Taipei, Taiwan, ⁸Chang Gung Memorial Hospital, Taoyuan County, Taiwan, ⁹University of Santo Tomas Hospital, Manila, Philippines, ¹⁰People's Hospital, Peking University Health Science Center, Beijing, China (People's Republic), ¹¹University of Malaya, Kuala Lumpur, Malaysia, ¹²Tokyo Women's Medical University School of Medicine, Tokyo, Japan, ¹³Peking University First Hospital, Beijing, China (People's Republic), ¹⁴Teaching (General) Hospital, Kandy, Sri Lanka, ¹⁵Tan Tock Seng Hospital, Singapore, Singapore, ¹⁶Keio University, Tokyo, Japan, ¹⁷Div. Rheumatology, Keio University, Tokyo, Japan, ¹⁸Melbourne Health, Parkville, Australia, ¹⁹Hanyang University Medical Center, Seoul, Republic of Korea, ²⁰Liverpool Hospital, Sydney, Australia, ²¹Flinders Medical Centre, Adelaide, Australia, ²²North Shore Hospital, Auckland, New Zealand, ²³Singapore General Hospital, Singapore, Singapore, ²⁴Auckland District Health Board, Auckland, New Zealand, ²⁵Counties Manukau Health, Auckland, New Zealand, ²⁶University of the Philippines, Quezon City, Philippines, ²⁷Janssen Asia Pacific, Seoul, Republic of Korea, ²⁸Janssen R&D, Spring House, PA, ²⁹University of Occupational and Environmental Health, Kitakyushu, Japan, ³⁰University of Hong Kong, Hong Kong, Hong Kong, ³¹University of Melbourne at St Vincent's Hospital, Melbourne, Australia, ³²Department of Rheumatology, Monash Health & Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, Australia, ³³School of Clinical Sciences at Monash Health, Monash University Faculty of Medicine, Nursing and Health Sciences, Monash Medical Centre Clayton, Melbourne, Australia

Meeting: ACR Convergence 2021

Keywords: LLDAS, Mortality, Systemic lupus erythematosus (SLE)

Session Information

Date: Sunday, November 7, 2021

Title: SLE – Diagnosis, Manifestations, & Outcomes Poster II: Manifestations (0855–0896)

Session Type: Poster Session B

Session Time: 8:30AM-10:30AM

Background/Purpose: Mortality in patients with systemic lupus erythematosus (SLE) is high compared to the general population. Attainment of the Lupus Low Disease Activity State (LLDAS) is validated as protective against adverse outcomes including organ damage accrual and flare. We examined whether LLDAS attainment provided protection against mortality in patients with SLE. In addition, we examined remission (Definitions for Remission in SLE (DORIS) definitions).

Methods: Data from a 13-country longitudinal SLE cohort on patients meeting either ACR or SLICC criteria were collected between 2013 and 2020 using standard case report files. LLDAS was defined as in Golder et al., 2019 (SLEDAI<4, no new activity, PGA <1, pred <7.5 mg/d, antimalarials (AM) and immunosuppressants (IS) allowed. Remission definitions were as in Vollenhoven et al, 2016 included clinical remission on treatment (CROT: clinical SLEDAI=0, AM and IS allowed, prednisolone <5 mg/d), and a variation disallowing glucocorticoid (CROT-off-steroid). Longitudinal associations of mortality were examined using survival (Cox regression) analysis.

Results: The study cohort included 4,020 SLE patients followed over a median of 2.6 years [IQR: 1.0 to 5.1] (Table 1). Ninety-one patients died during the study observation period; the crude mortality rate was ~ 7/1000 person-years. About 68% of deaths were related to infections; ~49% were related to SLE; ~24% related to cardiovascular causes and about 13% related to malignancy.

Disease activity and organ damage were strongly and independently associated with mortality. A 1 point increase in SLEDAI-2K was associated with an increased risk of mortality of 15% after accounting for confounders (adjusted HR: 1.15 (1.07, 1.23), p< 0.001). A 0.3-increase in PGA increased the risk of mortality by 33% (adjusted HR = 1.33 (1.13, 1.56), p=0.001). Every 1 unit increase in SDI score increased the mortality hazard by 53% (adjusted HR = 1.53 (1.38, 1.70), p< 0.001). While the associations of cumulative prednisolone exposure and flares with mortality were significant in univariable analysis, they attenuated in multivariable analysis.

48% of all patients achieved ≥50% observed time in LLDAS (LLDAS-50) but only 21% of those who died (Table 2). LLDAS-50 reduced mortality by 60% (adjusted HR = 0.40 (95% CI: 0.23, 0.69) p< 0.001) (Table 2). Clinical remission on treatment >50% of observed time (CROT-50) was achieved in 36% of patients and reduced mortality by 50% (HR = 0.50 (0.27, 0.92), p=0.026). A greater reduction in mortality was observed in patients who spent ≥50% time on CROT-off-steroid (HR=0.13 (0.02,0.96), p=0.045), but this was only achieved in 13% of patients (Table 2).

Conclusion: The attainment of LLDAS and DORIS remission conferred significant protection against mortality in SLE. LLDAS was more attainable than remission. Compared to LLDAS, clinical remission on treatment was not more protective, while clinical remission off steroids was maximally protective. Steroid free remission should be the goal of treatment in SLE.

Table 1 – Patient demographics of the study cohort

Table 2 – Longitudinal associations of LLDAS and DORIS remission attainment with mortality

Disclosures: R. Kandane-Rathnayake, None; V. Golder, None; W. Louthrenoo, None; Y. CHEN, None; J. Cho, None; A. Lateef, None; L. Hamijoyo, None; S. Luo, None; Y. Wu, None; S. Navarra, Biogen, 2, Boehringer Ingelheim, 6, Pfizer, 6, Novartis, 6, Johnson & Johnson, 6; L. Zamora, None; Z. Li, None; Y. An, None; S. Sockalingam, None; Y. Katsumata, Glaxo-Smithkline K.K., 6, Sanofi K.K., 6, AstraZeneca K.K., 6, Chugai Pharmaceutical Co., Ltd., 6, Pfizer Japan Inc., 6, Astellas Pharma Inc., 6, Mitsubishi Tanabe Pharma Corporation, 6, Janssen Pharmaceutical K.K., 6; M. Harigai, None; Y. Hao, None; Z. Zhang, None; B. Basnayake, None; M. Chan, DKSH, 1, 6, Johnson & Johnson, 1, AbbVie, 12, EULAR Congress 2021 registration fee; J. Kikuchi, None; T. Takeuchi, Astellas Pharma, 2, 5, 6, Chugai Pharmaceutical, 2, 5, 6, Asahi Kasei Pharma, 5, Mitsubishi Tanabe, 2, 5, 6, AbbVie, 5, 6, Daiichi Sankyo, 5, 6, Eisai, 5, 6, Shionogi, 5, Takeda, 5, UCB Japan, 5, Eli Lilly Japan, 2, 6, AYUMI, 6, Bristol-Myers Squibb, 6, Gilead Sciences, Inc., 6, Novartis, 6, Pfizer Japan, 6, Sanofi, 6, Dainippon Sumitomo, 6; S. Oon, Janssen, 6; S. Bae, None; S. O’Neill, None; F. Goldblatt, None; K. Gibson, Eli Lilly, 3; K. Ng, None; A. Law, None; N. Tugnet, None; S. Kumar, None; M. Tee, None; D. Yu, Janssen Asia Pacific, 3; C. Karyekar, Janssen Global Services, LLC, 3, 11; Y. Tanaka, Daiichi-Sankyo, 2, 5, 6, Eli Lilly, 6, Novartis, 6, YL Biologics, 6, Bristol-Myers Squibb, 6, Eisai, 5, 6, Chugai, 5, 6, AbbVie, 2, 5, 6, Astellas, 6, Pfizer, 6, Sanofi, 2, 6, Asahi-kasei, 5, 6, GSK, 2, 6, Mitsubishi-Tanabe, 5, 6, Gilead, 6, Janssen, 6, Takeda, 5, Ayumi, 2, Taisho, 2; C. Lau, None; M. Nikpour, None; A. Hoi, AstraZeneca, 2, 5, Janssen, 6, Abbvie, 6; E. Morand, Amgen, 2, AbbVie, 2, Biogen, 2, Bristol Myers Squibb, 2, 5, AstraZeneca, 2, 5, 6, Genentech, 2, Servier, 2, Capella Biosciences, 2, Eli Lilly, 5, 6, EMD Serono, 5, 6, Janssen, 2, 5, UCB, 2, GlaxoSmithKline, 2, 5.

To cite this abstract in AMA style:

Kandane-Rathnayake R, Golder V, Louthrenoo W, CHEN Y, Cho J, Lateef A, Hamijoyo L, Luo S, Wu Y, Navarra S, Zamora L, Li Z, An Y, Sockalingam S, Katsumata Y, Harigai M, Hao Y, Zhang Z, Basnayake B, Chan M, Kikuchi J, Takeuchi T, Oon S, Bae S, O’Neill S, Goldblatt F, Gibson K, Ng K, Law A, Tugnet N, Kumar S, Tee M, Yu D, Karyekar C, Tanaka Y, Lau C, Nikpour M, Hoi A, Morand E. Lupus Low Disease Activity State Attainment Provides Significant Protection Against Mortality: A Multi-National, Longitudinal Observational Study [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 9). https://acrabstracts.org/abstract/lupus-low-disease-activity-state-attainment-provides-significant-protection-against-mortality-a-multi-national-longitudinal-observational-study/. Accessed .

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