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  • Risk of flare and damage accrual after tapering glucocorticoids in modified serologically active clinically quiescent patients with systemic lupus erythematosus: a multinational observational cohort study

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Systemic lupus erythematosus
Risk of flare and damage accrual after tapering glucocorticoids in modified serologically active clinically quiescent patients with systemic lupus erythematosus: a multinational observational cohort study
  1. Yasuhiro Katsumata1,
  2. Eisuke Inoue1,2,
  3. Masayoshi Harigai1,
  4. Jiacai Cho3,
  5. Worawit Louthrenoo4,
  6. Alberta Hoi5,
  7. Vera Golder5,
  8. Chak Sing Lau6,
  9. Aisha Lateef7,
  10. Yi-Hsing Chen8,
  11. Shue-Fen Luo9,
  12. Yeong-Jian Jan Wu10,
  13. Laniyati Hamijoyo11,
  14. Zhanguo Li12,
  15. Sargunan Sockalingam13,
  16. Sandra Navarra14,
  17. Leonid Zamora15,
  18. Yanjie Hao16,
  19. Zhuoli Zhang17,
  20. Madelynn Chan18,
  21. Shereen Oon19,
  22. Kristine Ng20,
  23. Jun Kikuchi21,
  24. Tsutomu Takeuchi21,22,
  25. Fiona Goldblatt23,
  26. Sean O’Neill24,25,
  27. Nicola Tugnet26,
  28. Annie Hui Nee Law27,
  29. Sang-Cheol Bae28,29,30,
  30. Yoshiya Tanaka31,
  31. Naoaki Ohkubo31,
  32. Sunil Kumar32,
  33. Rangi Kandane-Rathnayake5,
  34. Mandana Nikpour33,34,
  35. Eric F Morand5
  36. For the Asia-Pacific Lupus Collaboration
  1. 1Division of Rheumatology, Department of Internal Medicine, Tokyo Women’s Medical University School of Medicine, Tokyo, Japan
  2. 2Showa University Research Administration Center, Showa University, Tokyo, Japan
  3. 3National University Hospital of Singapore, Singapore
  4. 4Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
  5. 5School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia
  6. 6The University of Hong Kong, Hong Kong, Hong Kong
  7. 7National University Health System, Singapore
  8. 8Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan
  9. 9Division of Rheumatology, Allergy, and Immunology, Chang Gung Memorial Hospital, Kuei Shan, Taiwan
  10. 10Department of Medicine, Division of Allergy, Immunology and Rheumatology, Chang Gung University College of Medicine, Tao-Yuan, Taiwan
  11. 11Rheumatology Division, Internal Medicine, Padjadjaran University, Bandung, Indonesia
  12. 12People’s Hospital Peking University Health Sciences Centre, Beijing, China
  13. 13Faculty of Medicine, University of Malaya, Kuala Lumpur, Wilayah Persekutuan, Malaysia
  14. 14University of Santo Tomas Hospital, Manila, The Philippines
  15. 15Faculty of Medicine and Surgery, University of Santo Tomas, Manila, The Philippines
  16. 16University of Melbourne at St Vincent’s Hospital, Fitzroy, Victoria, Australia
  17. 17Rheumatology and Clinical Immunology, Peking University First Hospital, Beijing, China
  18. 18Tan Tock Seng Hospital, Singapore
  19. 19Department of Medicine, The University of Melbourne at St Vincent’s Hospital, Fitzroy, Victoria, Australia
  20. 20Waitemata District Health Board, Auckland, New Zealand
  21. 21Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
  22. 22Saitama Medical University, Saitama, Japan
  23. 23Repatriation General Hospital, Daw Park, South Australia, Australia
  24. 24University of New South Wales, Sydney, New South Wales, Australia
  25. 25Ingham Institute of Applied Medical Research, Liverpool, New South Wales, Australia
  26. 26Auckland District Health Board, Auckland, New Zealand
  27. 27Rheumatology and Immunology, Singapore General Hospital, Singapore
  28. 28Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea (the Republic of)
  29. 29Hanyang University Institute for Rheumatology Research, Seoul, Korea (the Republic of)
  30. 30Hanyang Institute of Bioscience and Biotechnology, Seoul, Korea (the Republic of)
  31. 31First Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
  32. 32Middlemore Hospital, Auckland, New Zealand
  33. 33Department of Medicine, University of Melbourne, Fitzroy, Victoria, Australia
  34. 34The University of Sydney School of Public Health, Sydney, New South Wales, Australia
  1. Correspondence to Dr Yasuhiro Katsumata, Division of Rheumatology, Department of Internal Medicine, Tokyo Women’s Medical University School of Medicine, Tokyo, Japan; katsumata{at}twmu.ac.jp

Abstract

Objectives To assess the risk of flare and damage accrual after tapering glucocorticoids (GCs) in modified serologically active clinically quiescent (mSACQ) patients with systemic lupus erythematosus (SLE).

Methods Data from a 12-country longitudinal SLE cohort, collected prospectively between 2013 and 2020, were analysed. SLE patients with mSACQ defined as the state with serological activity (increased anti-dsDNA and/or hypocomplementemia) but without clinical activity, treated with ≤7.5 mg/day of prednisolone-equivalent GCs and not-considering duration, were studied. The risk of subsequent flare or damage accrual per 1 mg decrease of prednisolone was assessed using Cox proportional hazard models while adjusting for confounders. Observation periods were 2 years and censored if each event occurred.

Results Data from 1850 mSACQ patients were analysed: 742, 271 and 180 patients experienced overall flare, severe flare and damage accrual, respectively. Tapering GCs by 1 mg/day of prednisolone was not associated with increased risk of overall or severe flare: adjusted HRs 1.02 (95% CI, 0.99 to 1.05) and 0.98 (95% CI, 0.96 to 1.004), respectively. Antimalarial use was associated with decreased flare risk. Tapering GCs was associated with decreased risk of damage accrual (adjusted HR 0.96, 95% CI, 0.93 to 0.99) in the patients whose initial prednisolone dosages were >5 mg/day.

Conclusions In mSACQ patients, tapering GCs was not associated with increased flare risk. Antimalarial use was associated with decreased flare risk. Tapering GCs protected mSACQ patients treated with >5 mg/day of prednisolone against damage accrual. These findings suggest that cautious GC tapering is feasible and can reduce GC use in mSACQ patients.

  • Systemic Lupus Erythematosus
  • Disease Activity
  • Glucocorticoids
  • Hydroxychloroquine

Data availability statement

Data are available upon reasonable request.

https://doi.org/10.1136/ard-2023-225369

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    Data availability statement

    Data are available upon reasonable request.

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    Footnotes

    • Handling editor Josef S Smolen

    • Twitter @Cho Jiacai, @tuna0sashimi

    • Contributors YK and MH drafted the research proposal and protocol and wrote the first draft of the manuscript. YK and EI analysed the data. All authors except EI participated in patient recruitment and acquisition of the data. All authors were involved in drafting or revising this article critically for important intellectual content and approved the final version to be published. YK had full access to all relevant data from the study and takes responsibility for their integrity and the accuracy of the analyses performed. YK is responsible for the overall content as the guarantor.

    • Funding The APLC received unrestricted project grants from AstraZeneca, BMS, Eli Lily, Janssen, Merck Serono and UCB in support of data collection contributing to this work. The APLC received funding from GlaxoSmithKline Australia to conduct this research study. This work was also supported by the Japanese MEXT (the Ministry of Education, Culture, Sports, Science and Technology) KAKENHI (Grants-in-Aid for Scientific Research) (grant number, 20K08810). S-CB is supported in part by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2021R1A6A1A03038899).

    • Competing interests YK received honoraria from Asahi Kasei Pharma, Astellas Pharma, AstraZeneca K.K., Chugai Pharmaceutical, GlaxoSmithKline KK, Janssen Pharmaceutical KK, Mitsubishi Tanabe Pharma Corporation, Pfizer Japan, Sanofi KK. EI received honoraria from Bristol-Myers Squibb KK, Eisai and consulting fees from Nippontect Systems. MH received honoraria from AbbVie GK, Ayumi Pharmaceutical, Bristol-Myers Squibb K.K., Chugai Pharmaceutical, Eisai, Eli Lilly Japan K.K., GlaxoSmithKline K.K., Kissei Pharmaceutical, Nippon Boehringer Ingelheim, Pfizer Japan, Takeda Pharmaceutical, Teijin Pharma, consulting fees from AbbVie GK, Bristol-Myers Squibb K.K., Kissei Pharmaceutical, Nippon Boehringer Ingelheim, Teijin Pharma, grant/research support from AbbVie GK, Asahi Kasei Pharma, Astellas Pharma, Ayumi Pharmaceutical, Bristol-Myers Squibb K.K., Chugai Pharmaceutical, Daiichi-Sankyo, Eisai, Kissei Pharmaceutical, Mitsubishi Tanabe Pharma, Nippon Kayaku, Sekisui Medical, Shionogi, Taisho Pharmaceutical, Takeda Pharmaceutical, Teijin Pharma. AH received honoraria from UCB, Janssen, Sandoz, Eli Lilly, consulting fees from AbbVie, GSK and grant/research support from AstraZeneca, GSK, Bristol Myers Squibb, Janssen, Merck Serono. CSL received honoraria from AstraZeneca UK and consulting fee from AstraZeneca Pharmaceuticals LP. ZL received honoraria from Pfizer, Roche, Janssen, Abbott, AbbVie, Bristol Myers Squibb, MSD, Celgene, Eli Lilly, GSK, Novartis, UCB Pharma and consulting fees from Pfizer, Roche, Janssen, Abbott, AbbVie, Bristol Myers Squibb, MSD, Celgene, Eli Lilly, GSK, Novartis, UCB Pharma. SS received consulting fees from Pfizer, AstraZeneca, ZP Therapeutics and grant/research support from Pfizer, AstraZeneca, ZP Therapeutics. SVN received consulting fees from Biogen, Boehringer Ingelheim, AstraZeneca, grant/research support from Jannsen, Novartis, Pfizer, GSK and support for attending meetings from Biogen. SOon received royalty from Venetoclax. KN is on the advisory board for AbbVie. TT received honoraria from AbbVie GK, Chugai Pharmaceutical, Eli Lilly Japan K.K., Mitsubishi Tanabe Pharma, consulting fees from AbbVie GK, Chugai Pharmaceutical, Mitsubishi Tanabe Pharma and grant/research support from AbbVie GK, Eli Lilly Japan K.K., Mitsubishi Tanabe Pharma. YT received honoraria from AbbVie GK, Asahi Kasei Pharma, AstraZeneca K.K., Bristol-Myers Squibb K.K., Chugai Pharmaceutical, Eisai, Eli Lilly Japan K.K., Gilead Sciences, GlaxoSmithKline K.K., Nippon Boehringer Ingelheim, Pfizer Japan, Taiho Pharmaceutical, Taisho Pharmaceutical and grant/research support from Asahi Kasei Pharma, Chugai Pharmaceutical, Eisai, Mitsubishi Tanabe Pharma, Taisho Pharmaceutical. MN received honoraria from Actelion, GSK, Janssen, Pfizer, UCB, consulting fees from Boehringer Ingelheim, Certa Therapeutics, Eli Lilly, GSK, Janssen, Pfizer, UCB and grant/research support from Actelion, AstraZeneca, Bristol Myers Squibb, GSK, Janssen, UCB. EFM received honoraria from AstraZeneca, EMD Serono, Gilead, consulting fees from AstraZeneca, Bristol Myers Squibb, Biogen, Eli Lilly, EMD Serono, Novartis and grant/research support from AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Biogen, Eli Lilly, EMD Serono, Genentech, GSK, Janssen, UCB. All other authors declare no competing interests.

    • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.