Multicenter Study

. 2025 Jul 23;27(1):155.

doi: 10.1186/s13075-025-03622-8.

Prevalence and outcomes of a pilot definition of severe refractory systemic lupus erythematosus: observations from a multinational Asia-Pacific cohort

Rangi Kandane-Rathnayake¹, Worawit Louthrenoo², C S Lau³, Laniyati Hamijoyo⁴, Jiacai Cho⁵, Aisha Lateef⁶, Shue Fen Luo⁷, Yeong-Jian Wu⁸, Sandra Navarra⁹, Leonid Zamora⁹, Zhanguo Li¹⁰, Yi-Hsing Chen¹¹, Shereen Oon¹², Madelynn Chan¹³, Sargunan Sockalingam¹⁴, Yanjie Hao^{12

15}, Zhuoli Zhang¹⁵, Sang-Cheol Bae¹⁶, Jun Kikuchi¹⁷, Tsutomu Takeuchi^{17

18}, Yasuhiro Katsumata¹⁹, Bmdb Basnayake²⁰, Fiona Goldblatt²¹, Sean O'Neill^{22

23}, Kristine Pek Ling Ng²⁴, Nicola Tugnet²⁵, Mark Sapsford²⁶, Yih Jia Poh²⁷, Cherica Tee²⁸, Michael Tee²⁸, Naoaki Ohkubo²⁹, Adrienne O'Donnell Lefeber³⁰, Tamas Shisha³⁰, Yoshiya Tanaka²⁹, Vera Golder^{31

32}, Mandana Nikpour^{12

33}, Alberta Hoi^{31

32}, Peter Gergely³⁰, Eric Morand^{31

32}

Affiliations

¹ Centre for Inflammatory Diseases, School of Clinical Sciences, Monash University, VIC, Clayton, Australia. rangi.kandane-rathnayake@monash.edu.
² Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
³ Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Pokfulam, Hong Kong.
⁴ Department of Internal Medicine, Faculty of Medicine, Padjadjaran University, Bandung, Indonesia.
⁵ Rheumatology Division, Department of Medicine, National University Hospital, Singapore, Singapore.
⁶ Department of Rheumatology, Division of Medicine, Woodlands Health, Singapore, Singapore.
⁷ Department of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital, Taipei, Taiwan, Republic of China.
⁸ Department of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital, Keelung, Taiwan, Republic of China.
⁹ Section of Rheumatology, University of Santo Tomas Hospital, Manila, Philippines.
¹⁰ Department of Rheumatology and Immunology, People's Hospital, Peking University Health Science Center, Beijing, China.
¹¹ Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan, Republic of China.
¹² Department of Rheumatology, St Vincent's Hospital Melbourne, Fitzroy, VIC, Australia.
¹³ Department of Rheumatology, Allergy & Immunology, Tan Tock Seng Hospital, Tan Tock Seng, Singapore.
¹⁴ Department of Medicine, Universiti Malaya Medical Centre, Kuala Lumpur, Malaysia.
¹⁵ Rheumatology and Immunology department, Peking University First Hospital, Beijing, China.
¹⁶ Hanyang University Hospital for Rheumatic Diseases, Hanyang University Institute for Rheumatology Research and Hanyang Institute of Bioscience and Biotechnology, Seoul, South Korea.
¹⁷ Department of Internal Medicine, Keio University, Tokyo, Japan.
¹⁸ Department of Rheumatology and Applied/Clinical Immunology, Saitama Medical University, Saitama, Japan.
¹⁹ Department of Internal Medicine, Tokyo Women's Medical University, Tokyo, Japan.
²⁰ Department of Nephrology, Teaching Hospital Kandy, Kandy, Sri Lanka.
²¹ Department of Rheumatology, Flinders Medical Centre, Bedford Park, SA, Australia.
²² Rheumatology Department, Liverpool Hospital, Liverpool, NSW, Australia.
²³ University of Sydney, Sydney, NSW, Australia.
²⁴ Department of Rheumatology, North Shore Hospital, Health New Zealand Waitemata, Auckland, New Zealand.
²⁵ Department of Rheumatology, Greenlane Clinical Centre, Health New Zealand Auckland, Te Whatu Ora, Auckland, New Zealand.
²⁶ Department of Rheumatology, Middlemore Hospital, Health New Zealand Counties Manukau, Te Whatu Ora, Auckland, New Zealand.
²⁷ Department of Rheumatology and Immunology, Singapore General Hospital, Singapore, Singapore.
²⁸ College of Medicine, University of the Philippines, Manila, Philippines.
²⁹ The First Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
³⁰ Novartis Pharma, Basel, Switzerland.
³¹ Centre for Inflammatory Diseases, School of Clinical Sciences, Monash University, VIC, Clayton, Australia.
³² Rheumatology Department, Monash Health, Clayton, VIC, Australia.
³³ The University of Sydney School of Public Health, Sydney, NSW, Australia.

PMID: 40702560
PMCID: PMC12288243
DOI: 10.1186/s13075-025-03622-8

Multicenter Study

Prevalence and outcomes of a pilot definition of severe refractory systemic lupus erythematosus: observations from a multinational Asia-Pacific cohort

Rangi Kandane-Rathnayake et al. Arthritis Res Ther. 2025.

. 2025 Jul 23;27(1):155.

doi: 10.1186/s13075-025-03622-8.

Authors

Affiliations

¹ Centre for Inflammatory Diseases, School of Clinical Sciences, Monash University, VIC, Clayton, Australia. rangi.kandane-rathnayake@monash.edu.
² Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
³ Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Pokfulam, Hong Kong.
⁴ Department of Internal Medicine, Faculty of Medicine, Padjadjaran University, Bandung, Indonesia.
⁵ Rheumatology Division, Department of Medicine, National University Hospital, Singapore, Singapore.
⁶ Department of Rheumatology, Division of Medicine, Woodlands Health, Singapore, Singapore.
⁷ Department of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital, Taipei, Taiwan, Republic of China.
⁸ Department of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital, Keelung, Taiwan, Republic of China.
⁹ Section of Rheumatology, University of Santo Tomas Hospital, Manila, Philippines.
¹⁰ Department of Rheumatology and Immunology, People's Hospital, Peking University Health Science Center, Beijing, China.
¹¹ Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan, Republic of China.
¹² Department of Rheumatology, St Vincent's Hospital Melbourne, Fitzroy, VIC, Australia.
¹³ Department of Rheumatology, Allergy & Immunology, Tan Tock Seng Hospital, Tan Tock Seng, Singapore.
¹⁴ Department of Medicine, Universiti Malaya Medical Centre, Kuala Lumpur, Malaysia.
¹⁵ Rheumatology and Immunology department, Peking University First Hospital, Beijing, China.
¹⁶ Hanyang University Hospital for Rheumatic Diseases, Hanyang University Institute for Rheumatology Research and Hanyang Institute of Bioscience and Biotechnology, Seoul, South Korea.
¹⁷ Department of Internal Medicine, Keio University, Tokyo, Japan.
¹⁸ Department of Rheumatology and Applied/Clinical Immunology, Saitama Medical University, Saitama, Japan.
¹⁹ Department of Internal Medicine, Tokyo Women's Medical University, Tokyo, Japan.
²⁰ Department of Nephrology, Teaching Hospital Kandy, Kandy, Sri Lanka.
²¹ Department of Rheumatology, Flinders Medical Centre, Bedford Park, SA, Australia.
²² Rheumatology Department, Liverpool Hospital, Liverpool, NSW, Australia.
²³ University of Sydney, Sydney, NSW, Australia.
²⁴ Department of Rheumatology, North Shore Hospital, Health New Zealand Waitemata, Auckland, New Zealand.
²⁵ Department of Rheumatology, Greenlane Clinical Centre, Health New Zealand Auckland, Te Whatu Ora, Auckland, New Zealand.
²⁶ Department of Rheumatology, Middlemore Hospital, Health New Zealand Counties Manukau, Te Whatu Ora, Auckland, New Zealand.
²⁷ Department of Rheumatology and Immunology, Singapore General Hospital, Singapore, Singapore.
²⁸ College of Medicine, University of the Philippines, Manila, Philippines.
²⁹ The First Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
³⁰ Novartis Pharma, Basel, Switzerland.
³¹ Centre for Inflammatory Diseases, School of Clinical Sciences, Monash University, VIC, Clayton, Australia.
³² Rheumatology Department, Monash Health, Clayton, VIC, Australia.
³³ The University of Sydney School of Public Health, Sydney, NSW, Australia.

PMID: 40702560
PMCID: PMC12288243
DOI: 10.1186/s13075-025-03622-8

Abstract

Background: Emerging therapies have the potential to be used in patients with severe refractory systemic lupus erythematosus (srSLE), but no agreed definition of srSLE exists. We evaluated a pilot srSLE definition to assess whether a set of disease activity and treatment thresholds could identify patients with poor outcomes.

Methods: Data from a 13-country longitudinal SLE cohort, collected prospectively between 2013 and 2020 were analysed. srSLE was defined if a patient was in high disease activity (SLEDAI-2K ≥ 10) despite combination use of at least glucocorticoids (GC) and immunosuppressants (IS) at both the index and preceding visit. Synchronised to the index srSLE visit, we assessed disease activity, medication use and treat-to-target (T2T) endpoint attainment over 12 months (m).

Results: Of 3,744 patients studied, 578 (14%) had srSLE, in 1,810 visits. The median [IQR] SLEDAI-2K at the srSLE index visit was 12 [10, 14], which decreased to 6 [4, 10] at 6m and 12m. Most patients remained on combination anti-malarial, GC, and IS at all follow-up time points. The median [IQR] GC dose at the index visit was 10 [5, 20] mg/day; this reduced to 8 mg [5.0, 12.9] at 6m and 5 mg [5.0, 10.0] at 12m. Less than a quarter of patients attained LLDAS and only 1% attained GC-free remission over 12 months.

Conclusions: A draft definition of srSLE was clearly associated with poor outcomes. Work to evaluate multiple thresholds with which to define srSLE, and their outcomes, is warranted.

Keywords: Poor outcomes; Severe refractory disease; Systemic lupus erythematosus (SLE).

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Each site obtained local ethics approval to participate in the APLC research activities. Storage of the central dataset and analyses of the pooled data have been approved by the Monash University Human Research Ethics Committee (MUHREC Project ID 18778). All patients enrolled in the APLC have provided informed consent use their data for APLC research activities. Consent for publication: Not applicable. Competing interests: Rangi Kandane-Rathnayake– has received grants from BMS, GSK, Janssen and NovartisWorawit Louthrenoo - NoneCS Lau - NoneLaniyati Hamijoyo - NoneJiacai Cho - NoneAisha Lateef - NoneShue Fen Luo - NoneYeong-Jian Wu - NoneSandra Navarra - has received consulting fees from AstraZeneca, Biogen, Boehringer Ingelheim and Idorsia, and payment for lectures from AstraZeneca, Boehringer Ingelheim, GSK and Roche.Leonid Zamora - NoneZhanguo Li - has received consulting fees and royalties from Abbott, AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, GSK, Janssen, MSD, Novartis, Pfizer, Roche and UCB PharmaYi-Hsing Chen - NoneShereen Oon - NoneMadelynn Chan - NoneSargunan Sockalingam - NoneYanjie Hao - NoneZhuoli Zhang - NoneSang-Cheol Bae - supported in part by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2021R1A6A1A03038899)Jun Kikuchi - NoneYuko Kaneko - NoneTsutomu Takeuchi - NoneYasuhiro Katsumata - has received payment/honoraria from Asahi Kasei Pharma, AstraZeneca K.K., Astellas Pharma Inc., Chugai Pharmaceutical Co., Ltd, GSK K.K., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Corporation, Pfizer Japan Inc. and Sanofi K.K. ZZ has received payment/honoraria from AbbVie, AstraZeneca K.K., Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, GSK, Novartis, Pfizer, Roche, Sanofi, Janssen, UCB Pharma, and has participated in advisory boards for Beigene Ltd.Duminda Basnayake - NoneFiona Goldblatt - was a Director on the Board of the Australian Rheumatology Association at the time of the study.Sean O’Neill - NoneKristine (Pek Ling) Ng - NoneNicola Tugnet - NoneMark Sapsford - NoneYih Jia Poh - NoneCherica Tee - NoneMichael Tee - NoneNaoaki Ohkubo - NoneAdrianne O’Donnell Lefeber– is an employee of NovartisTamas Shisha - is an employee of NovartisYoshiya Tanaka - has received speaking fees and/or honoraria from Chugai, UCB, Abbvie, AstraZeneca, Eli-Lilly, Behringer-Ingelheim, GlaxoSmithKline, Eisai, IQVIA, Daiichi-Sankyo, Otsuka, Taisho, Gilead, Bristol-Mayers.Vera Golder - NoneMandana Nikpour - has received an Investigator Grant from the National Health and Medical Research Council of Australia (NHMRC GNT1176538), research grants from Boehringer Ingelheim and Janssen, consulting fees from AstraZeneca and GSK; honoraria for presentations from AstraZeneca, Boehringer Ingelheim and GSK, and support for conference attendance from Boehringer Ingelheim.Alberta Hoi - has received a research grant from AstraZeneca, consulting fees from EUSA Pharma (UK), GSK and UCB Australia, and speaker fees/honoraria from AbbVie, Eli Lilly, Janssen, Limbic, Moose Republic and Novartis.Peter Gergely– is an employ of NovartisEric Morand - has received consulting fees from AbbVie, AstraZeneca, Biogen, Bristol Myers Squibb, Genentech, Gilead, Janssen, Novartis, and EMD Serono.

Figures

**Fig. 1**
**legend**: Number of a) patients and b) visits with patients fulfilling the definition of srSLE

See this image and copyright information in PMC

References

1. Golder V, Kandane-Rathnayake R, Louthrenoo W, Chen YH, Cho J, Lateef A et al. Comparison of attainment and protective effects of lupus low disease activity state in patients with newly diagnosed versus established systemic lupus erythematosus. J Rheumatol. 2024. - PubMed
1. Golder V, Kandane-Rathnayake R, Li N, Louthrenoo W, Chen YH, Cho J et al. Association of sustained lupus low disease activity state with improved outcomes in systemic lupus erythematosus: a multinational prospective cohort study. Lancet Rheumatol. 2024. - PubMed
1. Kandane-Rathnayake R, Louthrenoo W, Hoi A, Luo SF, Wu YJ, Chen YH, et al. Not at target’: prevalence and consequences of inadequate disease control in systemic lupus erythematosus-a multinational observational cohort study. Arthritis Res Ther. 2022;24(1):70. - PMC - PubMed
1. Morand EF, Abreu G, Furie RA, Golder V, Tummala R. Lupus low disease activity state attainment in the phase 3 TULIP trials of anifrolumab in active systemic lupus erythematosus. Ann Rheum Dis. 2023. - PMC - PubMed
1. Morand E, Pike M, Merrill JT, van Vollenhoven R, Werth VP, Hobar C, et al. Deucravacitinib, a tyrosine kinase 2 inhibitor, in systemic lupus erythematosus: A phase II, randomized, Double-Blind, Placebo-Controlled trial. Arthritis Rheumatol. 2023;75:242–52. - PMC - PubMed

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Prevalence and outcomes of a pilot definition of severe refractory systemic lupus erythematosus: observations from a multinational Asia-Pacific cohort

Affiliations

Prevalence and outcomes of a pilot definition of severe refractory systemic lupus erythematosus: observations from a multinational Asia-Pacific cohort

Authors

Affiliations

Abstract

Conflict of interest statement

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References

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Medical

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