Association of Sustained Lupus Low Disease Activity State with Improved Outcomes in SLE: A Multinational Prospective Cohort Study

Vera Golder¹, Rangi Kandane-Rathnayake¹, Ning Li¹, Worawit Louthrenoo², Yi-Hsing Chen³, Jiacai Cho⁴, Aisha Lateef⁵, Laniyati Hamijoyo⁶, Luo Shue Fen⁷, Yeong-Jian Wu⁷, Sandra Navarra⁸, Leonid Zamora⁸, Zhanguo Li⁹, An Yuan¹⁰, Sargunan Sockalingam¹¹, Yasuhiro Katsumata¹², Masayoshi Harigai¹², Yanjie Hao¹³, Zhouli Zhang¹⁴, Duminda Basnayake¹⁵, Madelynn Chan¹⁶, Jun Kikuchi¹⁷, Tsutomu Takeuchi¹⁸, Sang-Cheol Bae¹⁹, Fiona Goldblatt²⁰, Shereen Oon²¹, Sean O'Neill²², Kathryn Gibson²², Kristine Ng²³, Hui Nee Annie Law²⁴, Nicole Tugnet²⁵, Sunil Kumar²⁶, Cherica Tee²⁷, Michael Tee²⁷, Yoshiya Tanaka²⁸, Chak Sing²⁹, Alberta Hoi³⁰, Mandana Nikpour³¹ and Eric Morand³², ¹Monash University, Clayton, Australia, ²Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand, ³Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan, ⁴National University Health System (NUHS), Singapore, Singapore, ⁵National University Hospital, Singapore, Singapore, ⁶Hasan Sadikin Hospital, Jakarta Selatan, Indonesia, ⁷Chang Gung Memorial Hospital, Taoyuan, Taiwan, ⁸University of Santo Tomas, Manila, Philippines, ⁹Peking University People's Hospital, Beijing, China, ¹⁰Peking University Health Science Center, Beijing, China, ¹¹University of Malaya, Kuala Lumpur, Kuala Lumpur, Malaysia, ¹²Division of Rheumatology, Department of Internal Medicine, Tokyo Women’s Medical University School of Medicine, Tokyo, Japan, ¹³The University of Melbourne, Melbourne, Australia, ¹⁴Peking University First Hospital, Beijing, China, ¹⁵Teaching Hospital Kandy, Kandy, Sri Lanka, ¹⁶Tan Tock Seng Hospital, Singapore, Singapore, ¹⁷Keio University School of Medicine, Tokyo, Japan, ¹⁸Keio University and Saitama Medical University, Tokyo, Japan, ¹⁹Hanyang University Medical Center, Seoul, Republic of Korea, ²⁰Flinders Medical Centre, Adelaide, Australia, ²¹St Vincent's Hospital, Fitzroy, Australia, ²²Liverpool Hospital, Sydney, Australia, ²³North Shore Hospital, Auckland, New Zealand, ²⁴Department of Rheumatology and Immunology, Singapore General Hospital, Singapore, Singapore, ²⁵Greenlane Clinical Centre, Auckland, New Zealand, ²⁶Middlemore Hospital, Auckland, New Zealand, ²⁷University of the Philippines, Quezon City, Philippines, ²⁸University of Occupational and Environmental Health, Kitakyusyu Fukuoka, Japan, ²⁹The University of Hong Kong, Pok Fu Lam, Hong Kong, ³⁰Monash Health, Melbourne, Australia, ³¹The University of Melbourne at St. Vincent's Hospital Melbourne, Melbourne, Australia, ³²Monash University, Victoria; Department of Rheumatology, Monash Health, Melbourne, Australia

Meeting: ACR Convergence 2022

Keywords: Outcome measures, Systemic lupus erythematosus (SLE)

Session Information

Date: Sunday, November 13, 2022

Title: Abstracts: SLE – Diagnosis, Manifestations, and Outcomes II: Complications

Session Type: Abstract Session

Session Time: 3:00PM-4:30PM

Background/Purpose: Since the initial prospective validation of the Lupus Low Disease Activity State (LLDAS), this treat-to-target endpoint has been studied in numerous other cohorts, with results supporting its protective associations against flare and damage accrual. The mean duration of follow up in the original prospective validation was 2 years, potentially impacting on the ability to detect longer term signals in disease flare and irreversible damage, which typically accrues slowly. In this study we aimed to assess long-term associations of sustained LLDAS with protection from damage accrual and flare.

Methods: Adult SLE patients were recruited and followed prospectively from May 2013 to Dec 2020. Patients with ≥2 visits and no missing data were included in analysis. Multi failure time-to-event (Cox regression) analyses were used to assess the impact of sustained LLDAS on irreversible damage accrual (SLICC damage index) and flare (SELENA flare index), with dose and threshold effects studied. DORIS Remission was similarly assessed.

Results: 3,770 SLE patients were followed for (mean ± SD) 3.1 ± 2.4 years, totalling 37,834 visits. Most patients (n 3,128, 76.2%) attained LLDAS on at least one occasion. Any single visit in LLDAS was associated with significant protection against subsequent damage accrual (HR 0.60, 95%CI 0.52-0.69, p< 0.001) and flare (HR 0.57, 95%CI 0.53-0.61, p< 0.001). 2,699 (71.6%) sustained LLDAS for >3 months. Increasing durations of sustained LLDAS from >3 to >24 months corresponded to increased protective effects against damage and flare, whether measured as a dose effect or as a threshold (Table 1). LLDAS was more attainable compared to Remission (61.7% of patients ever), whilst conferring a similar magnitude of protection against damage and flare for sustained time ( >3 months Remission: HR 0.69, 95%CI 0.60-0.80, p< 0.001, and HR 0.65, 95%CI 0.60-0.71, p< 0.001 respectively).

Conclusion: In this long term prospective cohort study, we confirm significant protective effects of LLDAS against damage accrual and flare, as well as demonstrating deepening protection with longer durations of sustained LLDAS. LLDAS is a more attainable treat-to-target endpoint than remission while having similar protective effects.

Dose effect – groups mutually exclusive;
Threshold effect – increasing threshold of sustained time;
Patients grouped based on maximum sustained time per patient

Disclosures: V. Golder, None; R. Kandane-Rathnayake, None; N. Li, None; W. Louthrenoo, None; Y. Chen, AbbVie, AstraZeneca, Astellas Pharma, Bristol-Myers Squibb, Chugai Pharma Taiwan, Inova Diagnostics, Eli Lilly, Johnson & Johnson, GlaxoSmithKline, MSD, Novartis, Roche, Sanofi, Thermo Fisher Scientific, UCB, United Biopharma, Agnitio Science & Technology, Boehringer Ingelheim, National Yang-Ming University, Pfizer Inc, Taiwan Ministry of Science and Technology, Taiwan Department of Health and Welfare, Taichung Veterans General Hospital and UCB, Gilead Sciences, Guigai; J. Cho, None; A. Lateef, None; L. Hamijoyo, None; L. Fen, None; Y. Wu, None; S. Navarra, Biogen, Astellas, Janssen, Novartis, Pfizer, Boehringer-Ingelheim, GlaxoSmithKline (GSK); L. Zamora, None; Z. Li, Pfizer, Eli Lilly, Novartis, GlaxoSmithKlein(GSK), AbbVie/Abbott, Roche; A. Yuan, None; S. Sockalingam, Pfizer, Roche, Novartis; Y. Katsumata, GlaxoSmithKline K.K., AstraZeneca K.K., Pfizer Japan Inc., Janssen Pharmaceutical K.K., Chugai Pharmaceutical Co., Ltd., Asahi Kasei Pharma, Sanofi K.K., Mitsubishi Tanabe Pharma Corporation, Astellas Pharma Inc.; M. Harigai, AbbVie Japan GK, Asahi Kasei Corp., Astellas Pharma Inc., Ayumi Pharmaceutical Co., Boehringer Ingelheim Japan, Inc., Bristol-Myers Squibb(BMS), Chugai Pharmaceutical Co., Ltd., Daiichi-Sankyo, Inc., Eisai Co., Ltd., Eli Lilly Japan K.K., Kaken Pharmaceutical Co., Ltd., Kissei Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Mochida Pharmaceutical Co., Ltd., Nippon Kayaku Co., Ltd., Nippon Shinyaku Co., Ltd., Pfizer Japan Inc., Taisho Pharmaceutical Co., Ltd., Teijin Pharma Ltd., UCB Japan Co., Ltd., Viatris Japan; Y. Hao, None; Z. Zhang, None; D. Basnayake, None; M. Chan, None; J. Kikuchi, None; T. Takeuchi, Astellas Pharma, Eli Lilly Japan, Gilead Sciences, AbbVie, Eisai Co., Ltd, Pfizer Japan Inc., Asahi Kasei, Chugai, Daiichi Sankyo, Dainippon Sumitomo Eisai, Mitsubishi-Tanabe, Shionogi, Takeda, UCB Japan, Ayumi Pharmaceutical Corporation, Bristol-Myers Squibb, Novartis, Sanofi; S. Bae, None; F. Goldblatt, None; S. Oon, None; S. O'Neill, None; K. Gibson, Eli Lilly Pty Ltd; K. Ng, None; H. Law, None; N. Tugnet, None; S. Kumar, None; C. Tee, None; M. Tee, None; Y. Tanaka, Lilly, AbbVie, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Pfizer, Mitsubishi Tanabe, GlaxoSmithKline, Asahi Kasei, Takeda, Astellas, Janssen, Novartis, Sanofi, UCB, YL Biologics, MSD, Ono, Taisho Toyama, Celltrion, Gilead, Boehringer-Ingelheim, Corrona, Kowa, Amgen, AstraZeneca, AstraZeneca, Eli Lilly; C. Sing, None; A. Hoi, None; M. Nikpour, Janssen, AstraZeneca, GlaxoSmithKlein(GSK), Boehringer-Ingelheim, Bristol-Myers Squibb(BMS); E. Morand, AbbVie/Abbott, Amgen, AstraZeneca, Biogen, Bristol-Myers Squibb(BMS), Eli Lilly, Genentech, GlaxoSmithKlein(GSK), Janssen, Novartis, Servier, UCB, EMD Serono, Billerica, MA, USA.

To cite this abstract in AMA style:

Golder V, Kandane-Rathnayake R, Li N, Louthrenoo W, Chen Y, Cho J, Lateef A, Hamijoyo L, Fen L, Wu Y, Navarra S, Zamora L, Li Z, Yuan A, Sockalingam S, Katsumata Y, Harigai M, Hao Y, Zhang Z, Basnayake D, Chan M, Kikuchi J, Takeuchi T, Bae S, Goldblatt F, Oon S, O'Neill S, Gibson K, Ng K, Law H, Tugnet N, Kumar S, Tee C, Tee M, Tanaka Y, Sing C, Hoi A, Nikpour M, Morand E. Association of Sustained Lupus Low Disease Activity State with Improved Outcomes in SLE: A Multinational Prospective Cohort Study [abstract]. Arthritis Rheumatol. 2022; 74 (suppl 9). https://acrabstracts.org/abstract/association-of-sustained-lupus-low-disease-activity-state-with-improved-outcomes-in-sle-a-multinational-prospective-cohort-study/. Accessed .

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