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

Yasuhiro Katsumata¹, Eisuke Inoue^{2

3}, Masayoshi Harigai², Jiacai Cho⁴, Worawit Louthrenoo⁵, Alberta Hoi⁶, Vera Golder⁶, Chak Sing Lau⁷, Aisha Lateef⁸, Yi-Hsing Chen⁹, Shue-Fen Luo¹⁰, Yeong-Jian Jan Wu¹¹, Laniyati Hamijoyo¹², Zhanguo Li¹³, Sargunan Sockalingam¹⁴, Sandra Navarra¹⁵, Leonid Zamora¹⁶, Yanjie Hao¹⁷, Zhuoli Zhang¹⁸, Madelynn Chan¹⁹, Shereen Oon²⁰, Kristine Ng²¹, Jun Kikuchi²², Tsutomu Takeuchi^{22

23}, Fiona Goldblatt²⁴, Sean O'Neill^{25

26}, Nicola Tugnet²⁷, Annie Hui Nee Law²⁸, Sang-Cheol Bae^{29

30

31}, Yoshiya Tanaka³², Naoaki Ohkubo³², Sunil Kumar³³, Rangi Kandane-Rathnayake⁶, Mandana Nikpour^{34

35}, Eric F Morand⁶; Asia-Pacific Lupus Collaboration

Affiliations

¹ Division of Rheumatology, Department of Internal Medicine, Tokyo Women's Medical University School of Medicine, Tokyo, Japan katsumata@twmu.ac.jp.
² Division of Rheumatology, Department of Internal Medicine, Tokyo Women's Medical University School of Medicine, Tokyo, Japan.
³ Showa University Research Administration Center, Showa University, Tokyo, Japan.
⁴ National University Hospital of Singapore, Singapore.
⁵ Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
⁶ School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia.
⁷ The University of Hong Kong, Hong Kong, Hong Kong.
⁸ National University Health System, Singapore.
⁹ Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan.
¹⁰ Division of Rheumatology, Allergy, and Immunology, Chang Gung Memorial Hospital, Kuei Shan, Taiwan.
¹¹ Department of Medicine, Division of Allergy, Immunology and Rheumatology, Chang Gung University College of Medicine, Tao-Yuan, Taiwan.
¹² Rheumatology Division, Internal Medicine, Padjadjaran University, Bandung, Indonesia.
¹³ People's Hospital Peking University Health Sciences Centre, Beijing, China.
¹⁴ Faculty of Medicine, University of Malaya, Kuala Lumpur, Wilayah Persekutuan, Malaysia.
¹⁵ University of Santo Tomas Hospital, Manila, The Philippines.
¹⁶ Faculty of Medicine and Surgery, University of Santo Tomas, Manila, The Philippines.
¹⁷ University of Melbourne at St Vincent's Hospital, Fitzroy, Victoria, Australia.
¹⁸ Rheumatology and Clinical Immunology, Peking University First Hospital, Beijing, China.
¹⁹ Tan Tock Seng Hospital, Singapore.
²⁰ Department of Medicine, The University of Melbourne at St Vincent's Hospital, Fitzroy, Victoria, Australia.
²¹ Waitemata District Health Board, Auckland, New Zealand.
²² Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
²³ Saitama Medical University, Saitama, Japan.
²⁴ Repatriation General Hospital, Daw Park, South Australia, Australia.
²⁵ University of New South Wales, Sydney, New South Wales, Australia.
²⁶ Ingham Institute of Applied Medical Research, Liverpool, New South Wales, Australia.
²⁷ Auckland District Health Board, Auckland, New Zealand.
²⁸ Rheumatology and Immunology, Singapore General Hospital, Singapore.
²⁹ Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea (the Republic of).
³⁰ Hanyang University Institute for Rheumatology Research, Seoul, Korea (the Republic of).
³¹ Hanyang Institute of Bioscience and Biotechnology, Seoul, Korea (the Republic of).
³² First Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
³³ Middlemore Hospital, Auckland, New Zealand.
³⁴ Department of Medicine, University of Melbourne, Fitzroy, Victoria, Australia.
³⁵ The University of Sydney School of Public Health, Sydney, New South Wales, Australia.

PMID: 38423757
DOI: 10.1136/ard-2023-225369

Free article

Observational Study

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

Yasuhiro Katsumata et al. Ann Rheum Dis. 2024.

Free article

. 2024 Jul 15;83(8):998-1005.

doi: 10.1136/ard-2023-225369.

Authors

Affiliations

¹ Division of Rheumatology, Department of Internal Medicine, Tokyo Women's Medical University School of Medicine, Tokyo, Japan katsumata@twmu.ac.jp.
² Division of Rheumatology, Department of Internal Medicine, Tokyo Women's Medical University School of Medicine, Tokyo, Japan.
³ Showa University Research Administration Center, Showa University, Tokyo, Japan.
⁴ National University Hospital of Singapore, Singapore.
⁵ Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
⁶ School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia.
⁷ The University of Hong Kong, Hong Kong, Hong Kong.
⁸ National University Health System, Singapore.
⁹ Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan.
¹⁰ Division of Rheumatology, Allergy, and Immunology, Chang Gung Memorial Hospital, Kuei Shan, Taiwan.
¹¹ Department of Medicine, Division of Allergy, Immunology and Rheumatology, Chang Gung University College of Medicine, Tao-Yuan, Taiwan.
¹² Rheumatology Division, Internal Medicine, Padjadjaran University, Bandung, Indonesia.
¹³ People's Hospital Peking University Health Sciences Centre, Beijing, China.
¹⁴ Faculty of Medicine, University of Malaya, Kuala Lumpur, Wilayah Persekutuan, Malaysia.
¹⁵ University of Santo Tomas Hospital, Manila, The Philippines.
¹⁶ Faculty of Medicine and Surgery, University of Santo Tomas, Manila, The Philippines.
¹⁷ University of Melbourne at St Vincent's Hospital, Fitzroy, Victoria, Australia.
¹⁸ Rheumatology and Clinical Immunology, Peking University First Hospital, Beijing, China.
¹⁹ Tan Tock Seng Hospital, Singapore.
²⁰ Department of Medicine, The University of Melbourne at St Vincent's Hospital, Fitzroy, Victoria, Australia.
²¹ Waitemata District Health Board, Auckland, New Zealand.
²² Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
²³ Saitama Medical University, Saitama, Japan.
²⁴ Repatriation General Hospital, Daw Park, South Australia, Australia.
²⁵ University of New South Wales, Sydney, New South Wales, Australia.
²⁶ Ingham Institute of Applied Medical Research, Liverpool, New South Wales, Australia.
²⁷ Auckland District Health Board, Auckland, New Zealand.
²⁸ Rheumatology and Immunology, Singapore General Hospital, Singapore.
²⁹ Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea (the Republic of).
³⁰ Hanyang University Institute for Rheumatology Research, Seoul, Korea (the Republic of).
³¹ Hanyang Institute of Bioscience and Biotechnology, Seoul, Korea (the Republic of).
³² First Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
³³ Middlemore Hospital, Auckland, New Zealand.
³⁴ Department of Medicine, University of Melbourne, Fitzroy, Victoria, Australia.
³⁵ The University of Sydney School of Public Health, Sydney, New South Wales, Australia.

PMID: 38423757
DOI: 10.1136/ard-2023-225369

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.

Keywords: Disease Activity; Glucocorticoids; Hydroxychloroquine; Systemic Lupus Erythematosus.

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Conflict of interest statement

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.

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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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

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