SMART-SLE: serology monitoring and repeat testing in systemic lupus erythematosus—an analysis of anti-double-stranded DNA monitoring

Author:

Yeo Ai Li1ORCID,Kandane-Rathnayake Rangi1ORCID,Koelmeyer Rachel1ORCID,Golder Vera1ORCID,Louthrenoo Worawit2ORCID,Chen Yi-Hsing3ORCID,Cho Jiacai4ORCID,Lateef Aisha4ORCID,Hamijoyo Laniyati5ORCID,Luo Shue-Fen6ORCID,Wu Yeong-Jian J6ORCID,Navarra Sandra V7ORCID,Zamora Leonid7ORCID,Li Zhanguo8ORCID,An Yuan8,Sockalingam Sargunan9ORCID,Katsumata Yasuhiro10ORCID,Harigai Masayoshi10ORCID,Hao Yanjie11ORCID,Zhang Zhuoli11ORCID,Basnayake B M D B12,Chan Madelynn13ORCID,Kikuchi Jun14ORCID,Takeuchi Tsutomu14ORCID,Bae Sang-Cheol15ORCID,Oon Shereen16ORCID,O’Neill Sean17ORCID,Goldblatt Fiona18ORCID,Ng Kristine (Pek Ling)19,Law Annie20ORCID,Tugnet Nicola21,Kumar Sunil22,Tee Cherica23ORCID,Tee Michael23ORCID,Ohkubo Naoaki24,Tanaka Yoshiya24ORCID,Lau Chak Sing25ORCID,Nikpour Mandana16ORCID,Hoi Alberta1ORCID,Leech Michelle1,Morand Eric F1ORCID,

Affiliation:

1. School of Clinical Sciences at Monash Health, Faculty of Medicine, Nursing & Health Sciences, Monash University , Clayton, Victoria, Australia

2. Department of Medicine, Faculty of Medicine, Chiang Mai University , Chiang Mai, Thailand

3. Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital , Taichung, Taiwan

4. Rheumatology Divsion, National University Hospital , Singapore

5. Department of Medicine, University of Padjadjaran , Bandung, Indonesia

6. Department of Rheumatology, Chang Gung Memorial Hospital , Guishan Township, Taiwan

7. Joint and Bone Center, University of Santo Tomas Hospital , Manila, Philippines

8. Department of Rheumatology and Immunology, People’s Hospital Peking University Health Sciences Centre , Beijing, China

9. Department of Medicine, University of Malaya , Kuala Lumpur, Malaysia

10. Institute of Rheumatology, Tokyo Women’s Medical University , Tokyo, Japan

11. Rheumatology and Immunology Department, Peking University First Hospital , Beijing, China

12. Division of Nephrology, Teaching Hospital , Kandy, Sri Lanka

13. Department of Rheumatology, Allergy and Immunology Tan Tock Seng Hospital , Singapore

14. Division of Rheumatology, Department of Internal Medicine, Keio University , Tokyo, Japan

15. Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases and Hanyang University Institute for Rheumatology Research and Hanyang University Institute of Bioscience and Biotechnology , Seoul, South Korea

16. Department of Medicine, The University of Melbourne at St Vincent’s Hospital , Fitzroy, Victoria, Australia

17. Rheumatology Department, Level 1 Liverpool Hospital , Liverpool, NSW, Australia

18. Rheumatology Unit, Royal Adelaide Hospital and Flinders Medical Centre , Adelaide, South Australia, Australia

19. Department of Medicine, Waitemata District Health Board , Auckland, New Zealand

20. Singapore General Hospital , Singapore

21. Department of Rheumatology, Auckland District Health Board , Auckland, New Zealand

22. Department of Rheumatology, Middlemore Hospital , Auckland, New Zealand

23. University of the Philippines , Quezon City, Philippines

24. The First Department of Internal Medicine, University of Occupational and Environmental Health , Kitakyushu, Japan

25. Division of Rheumatology and Clinical Immunology, University of Hong Kong , Hong Kong, Hong Kong, China

Abstract

Abstract Objective Disease activity monitoring in SLE includes serial measurement of anti-double stranded-DNA (dsDNA) antibodies, but in patients who are persistently anti-dsDNA positive, the utility of repeated measurement is unclear. We investigated the usefulness of serial anti-dsDNA testing in predicting flare in SLE patients who are persistently anti-dsDNA positive. Methods Data were analysed from patients in a multinational longitudinal cohort with known anti-dsDNA results from 2013 to 2021. Patients were categorized based on their anti-dsDNA results as persistently negative, fluctuating or persistently positive. Cox regression models were used to examine longitudinal associations of anti-dsDNA results with flare. Results Data from 37 582 visits of 3484 patients were analysed. Of the patients 1029 (29.5%) had persistently positive anti-dsDNA and 1195 (34.3%) had fluctuating results. Anti-dsDNA expressed as a ratio to the normal cut-off was associated with the risk of subsequent flare, including in the persistently positive cohort (adjusted hazard ratio [HR] 1.56; 95% CI: 1.30, 1.87; P < 0.001) and fluctuating cohort (adjusted HR 1.46; 95% CI: 1.28, 1.66), both for a ratio >3. Both increases and decreases in anti-dsDNA more than 2-fold compared with the previous visit were associated with increased risk of flare in the fluctuating cohort (adjusted HR 1.33; 95% CI: 1.08, 1.65; P = 0.008) and the persistently positive cohort (adjusted HR 1.36; 95% CI: 1.08, 1.71; P = 0.009). Conclusion Absolute value and change in anti-dsDNA titres predict flares, including in persistently anti-dsDNA positive patients. This indicates that repeat monitoring of dsDNA has value in routine testing.

Funder

AstraZeneca

Eli Lilly

Publisher

Oxford University Press (OUP)

Subject

Pharmacology (medical),Rheumatology

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