2067: Predictors of Organ Damage Accrual by Domains

Rangi Kandane-Rathnayake¹, Ning Li¹, Vera Golder¹, Worawit Louthrenoo², Yi-Hsin Chen³, Jiacai Cho⁴, Aisha Lateef⁵, Laniyati Hamijoyo⁶, Luo Shue Fen⁷, Yeong-Jian Wu⁷, Sandra Navarra⁸, Leonid Zamora⁹, Zhanguo Li¹⁰, An Yuan¹¹, Sargunan Sockalingam¹², Yasuhiro Katsumata¹³, Masayoshi Harigai¹³, Yanjie Hao¹⁴, Zhouli Zhang¹⁵, Madelynn Chan¹⁶, Jun Kikuchi¹⁷, Tsutomu Takeuchi¹⁸, Shereen Oon¹⁹, Sang-Cheol Bae²⁰, Fiona Goldblatt²¹, Sean O'Neill²², Kathy Gibson²², Kristine Ng²³, Hui Nee Annie Law²⁴, Duminda Basnayake²⁵, Nicole Tugnet²⁶, Sunil Kumar²⁷, Cherica Tee²⁸, Michael Tee²⁸, Yoshiya Tanaka²⁹, Chak Sing³⁰, Mandana Nikpour³¹, Alberta Hoi³² and Eric Morand³³, ¹Monash University, Clayton, Australia, ²Chiang Mai University, Chiang Mai, Thailand, ³Taichung 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, ⁹University of Santo Tomas Hospital, Manila, Philippines, ¹⁰People's Hospital, Peking University Health Science Center, Beijing, China, ¹¹Peking University Health Science Center, Beijing, China, ¹²University of Malaya, Kuala Lumpur, Malaysia, ¹³Division of Rheumatology, Department of Internal Medicine, Tokyo Women’s Medical University School of Medicine, Tokyo, Japan, ¹⁴The University of Melbourne, Melbourne, Australia, ¹⁵Peking University First Hospital, Beijing, China, ¹⁶Tan Tock Seng Hospital, Singapore, Singapore, ¹⁷Keio University, Tokyo, Japan, ¹⁸Keio University and Saitama Medical University, Tokyo, Japan, ¹⁹St Vincent's Hospital, Fitzroy, Australia, ²⁰Hanyang University Medical Center, Seoul, Republic of Korea, ²¹Flinders Medical Centre, Adelaide, Australia, ²²Liverpool Hospital, Sydney, Australia, ²³North Shore Hospital, Auckland, New Zealand, ²⁴Department of Rheumatology and Immunology, Singapore General Hospital, Singapore, Singapore, ²⁵Teaching Hospital Kandy, Kandy, Sri Lanka, ²⁶Greenlane Clinical Centre, Auckland, New Zealand, ²⁷Middlemore Hospital, Auckland, New Zealand, ²⁸University of the Philippines, Quezon City, Philippines, ²⁹University of Occupational and Environmental Health, Kitakyusyu Fukuoka, Japan, ³⁰The University of Hong Kong, Pok Fu Lam, Hong Kong, ³¹The University of Melbourne at St. Vincent's Hospital Melbourne, Melbourne, Australia, ³²Monash Health, Melbourne, Australia, ³³Monash University, Victoria; Department of Rheumatology, Monash Health, Melbourne, Australia

Background/Purpose: Prevention of organ damage is one of the main treatment goals in systemic lupus erythematosus (SLE).The SLICC/ACR Damage Index (SDI) is used to quantify damage in 12 organ systems; ocular, neuropsychiatric (NP), renal, pulmonary, cardiovascular (CV), peripheral vascular (PV), gastrointestinal (GI), musculoskeletal (MSK), skin, premature gonadal failure (PGF), diabetes and malignancy [1]. Most studies report a summed damage score >0 as an indication of organ damage. However, few studies report the frequency and predictors of damage according to organ system domains.

We examined the predictors of overall damage accrual (DA) as well as DA in organ domains and assessed whether risk factors for overall DA capture those associated with domain-specific DA.

Methods: Data from a 13-country longitudinal SLE cohort were collected between 2013 and 2020 using standard templates. Organ damage was assessed annually using SDI; at each visit disease activity was assessed using SLE Disease Activity Index (SLEDAI-2K), physician global assessment (PGA) and flare (SELENA-SLEDAI Flare Index). A series of multi-failure, multivariate models were carried out to examine the risk factors associated with overall and domain-specific DA. Total time from cohort entry to the occurrence of new damage accrual was fitted using the Prentice, Williams and Peterson (PWP-TT) models.

Results: For overall DA, older age and living in a low gross domestic product (GDP) country were strong predictors, as was cumulative prednisolone dose (Figure 2). Flare number and time adjusted mean SLEDAI-2K (AMS) increased the risk of subsequent overall DA by 7% (HR=1.07 (95%CI: 1.02, 1.12), and 6% (HR=1.06 (95%CI: 1.03, 1.10), respectively, as did CNS, renal, and serositis activity. Likewise, the presence of organ damage in several domains including NP, GI, MSK and diabetes was strongly associated with subsequent overall DA. For organ domain specific DA, Figure 2 shows that risk factors differed between domains. Existing organ damage in diabetes and skin domains was strongly predictive of subsequent DA in multiple domains. Smoking was a significant risk factor for CV, PV and skin DA. Male sex was associated with malignancy DA, while Asian ethnicity conferred greater risk of ocular, MSK, and diabetic DA but was protective against PV DA. Anti-malarial (AM) use was protective from renal and pulmonary DA but was a significant risk factor for MSK DA. Immunosuppressant use was strongly associated with ocular DA (Figure 2).

Conclusion: In SLE, risk factors for overall DA have highly variable associations with domain-specific DA. Domain-specific damage should be reported in studies of SLE outcomes.

References
1. Stoll T, Seifert B, Isenberg DA. SLICC/ACR Damage Index is valid, and renal and pulmonary organ scores are predictors of severe outcome in patients with systemic lupus erythematosus. Br J Rheumatol. 1996 Mar; 35(3):248-254.
Figure 1 – Frequency of patients with organ damage and damage accrual stratified by a) organ domain, and by b) number of domains. NP = neuropsychiatric, Pulm .= pulmonary, CVD = cardiovascular, PV = peripheral vascular, GI = gastrointestinal, MSK = musculoskeletal, skin, PGF = premature gonadal failure (PGF), DB = diabetes, and Malig. = malignancy

Figure 2 – A summary of independent predictors of organ damage accrual in subsequent visits, stratified by domain. P < 0.05 in yellow; 0.05
Disclosures: R. Kandane-Rathnayake, None; N. Li, None; V. Golder, None; W. Louthrenoo, None; Y. Chen, None; 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, None; A. Yuan, None; S. Sockalingam, None; 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; 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. Oon, None; S. Bae, None; F. Goldblatt, None; S. O'Neill, None; K. Gibson, Eli Lilly Pty Ltd; K. Ng, None; H. Law, None; D. Basnayake, 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; M. Nikpour, Janssen, AstraZeneca, GlaxoSmithKlein(GSK), Boehringer-Ingelheim, Bristol-Myers Squibb(BMS); A. Hoi, None; 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.