0996: Tapering of Corticosteroids or Immunosuppressive Therapy in Stable SLE: A Comparison of Complete Remission, Clinical Remission and Lupus Low Disease Activity State in Protection Against Flares

Jiacai Cho¹, liang shen², Molla Huq³, Rangi Kandane-Rathnayake⁴, Vera Golder⁴, Worawit Louthrenoo⁵, Yi-Hsin Chen⁶, Laniyati Hamijoyo⁷, Luo Shue Fen⁸, Yeong-Jian Wu⁸, Leonid Zamora⁹, Zhouli Zhang¹⁰, An Yuan¹¹, Sargunan Sockalingam¹², Yasuhiro Katsumata¹³, Masayoshi Harigai¹³, Yanjie Hao³, Zhanguo Li¹⁴, Duminda Basnayake¹⁵, Madelynn Chan¹⁶, Jun Kikuchi¹⁷, Tsutomu Takeuchi¹⁸, Sang-Cheol Bae¹⁹, Fiona Goldblatt²⁰, Shereen Oon²¹, Sean O'Neill²², Kathy Gibson²², Kristine Ng²³, Hui Nee Annie Law²⁴, Nicole Tugnet²⁵, Sunil Kumar²⁶, Cherica Tee²⁷, Michael Tee²⁷, Naoaki Ohkubo²⁸, Yoshiya Tanaka²⁸, Sandra Navarra²⁹, Chak Sing³⁰, Alberta Hoi³¹, Eric Morand³², Mandana Nikpour³³ and Aisha Lateef³⁴, ¹National University Health System (NUHS), Singapore, Singapore, ²National University of Singapore, Singapore, Singapore, ³The University of Melbourne, Melbourne, Australia, ⁴Monash University, Clayton, Australia, ⁵Chiang Mai University, Chiang Mai, Thailand, ⁶Taichung Veterans General Hospital, Taichung, Taiwan, ⁷Hasan Sadikin Hospital, Jakarta Selatan, Indonesia, ⁸Chang Gung Memorial Hospital, Taoyuan, Taiwan, ⁹University of Santo Tomas Hospital, Manila, Philippines, ¹⁰Peking University First Hospital, 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, ¹⁴People's Hospital, Peking University Health Science Center, Beijing, China, ¹⁵Teaching Hospital Kandy, Kandy, Sri Lanka, ¹⁶Tan Tock Seng Hospital, Singapore, Singapore, ¹⁷Keio University, Tokyo, Japan, ¹⁸Keio University and Saitama Medical University, Tokyo, Japan, ¹⁹Hanyang University Medical Center, Seoul, Republic of Korea, ²⁰Royal Adelaide Hospital and Flinders Medical Centre, Adelaide, Australia, ²¹St Vincent's Hospital, Fitzroy, Australia, ²²Liverpool Hospital, Sydney, Australia, ²³North Shore Hospital, Auckland, New Zealand, ²⁴Department of Rheumatology and Immunology, Singapore General Hospital, Singapore, Singapore, ²⁵Greenlane Clinical Centre, Auckland, New Zealand, ²⁶Middlemore Hospital, Auckland, New Zealand, ²⁷University of the Philippines, Quezon City, Philippines, ²⁸University of Occupational and Environmental Health, Kitakyusyu Fukuoka, Japan, ²⁹University of Santo Tomas, Manila, Philippines, ³⁰The University of Hong Kong, Pok Fu Lam, Hong Kong, ³¹Monash Health, Melbourne, Australia, ³²Monash University, Victoria; Department of Rheumatology, Monash Health, Melbourne, Australia, ³³The University of Melbourne at St. Vincent's Hospital Melbourne, Melbourne, Australia, ³⁴National University Hospital, Singapore, Singapore

Background/Purpose: Proposed targets of SLE treatment include lupus low disease activity state (LLDAS), clinical remission and complete remission. Whether treatment can be tapered after achieving these targets and whether tapering will be safer in deeper states of remission compared to LLDAS are unknown.

Methods: We collected data from SLE patients (ACR/SLICC criteria) prospectively between 2013 to 2020 from 13 Asia-pacific countries. Disease activity was captured at each visit using SLEDAI-2K. We defined flares using SELEA-SLEDAI Flare Index. Tapering was defined as any decrease in dose of corticosteroids or immunosuppressive therapy (MMF, CSA, AZA, LEF, MTX or tacrolimus). We studied all visits that had achieved target, including LLDAS¹, 2021 DORIS definition of clinical remission (clinical SLEDAI=0, PGA< 0.5, prednisolone ≤5mg/day)² or DORIS complete remission on therapy (SLEDAI-2K=0, PGA< 0.5, prednisolone ≤5mg/day)³. Using multivariable generalized estimating equations, we compared flares at the subsequent visit, after drug tapering versus continuing the same therapy.

We then further analyzed tapering that occurred across visits by grouping consecutive visits into a single “tapering attempt”. A tapering attempt began with any taper of corticosteroids or immunosuppressive therapy at one of the target SLE states and ended at a visit when the dose of corticosteroid or immunosuppressive agent was increased. We used multivariable COX-proportional hazards to analyze the time to first flare, comparing attempts which had begun in LLDAS, clinical remission and complete remission.

Results: We included 3002 patients and 14808 patient-visits that had achieved one of the target SLE states (LLDAS, clinical remission or complete remission). Tapering occurred in 3521 visits (23.8%) and 11287 (76.2%) continued on the same therapy. 1679 flares (12.8%) were captured at the next visit. Tapering was associated with 1.24 higher odds of flare compared to continuing same therapy (p< 0.01). Other statistically significant associations included use of antimalarials, country, adjusted mean SLEDAI, disease duration and cumulative LLDAS/remission duration before taper (Table 1).

We recorded 2095 tapering attempts, of which 41.1%, 28.4% and 30.5% were initiated in LLDAS, clinical remission and complete remission respectively. The median (IQR) time to flare was 238 (33-443) days. Tapering attempts that were initiated in complete remission had a significantly longer time to first flare compared to attempts that were initiated in clinical remission or LLDAS (HR 0.79, p=0.009, Figure 1). Other significant variables associated with longer time to flare included country, duration of LLDAS/remission more than 30 days before taper, older age, shorter disease duration and lower adjusted mean SLEDAI (Table 2).

Conclusion: Tapering of corticosteroids or immunosuppressive therapy in stable SLE was associated with increased flares. Attaining complete remission was more protective against flares upon drug tapering as compared to attaining LLDAS or clinical remission. Drug tapering should be carefully considered in stable SLE patients irrespective with LLDAS or either type of remission.
* Includes MMF, CSA, AZA, LEF, MTX or tacrolimus
β Compared to continuation of therapy without tapering
# LLDAS; Lupus Low Disease Activity State; SLEDAI-2K≤4, PGA < 0.5, prednisolone ≤7.5mg/day)
^Clinical remission; clinical SLEDAI=0, PGA < 0.5, prednisolone ≤5mg/day
α Compared to Complete remission; SLEDAI-2K=0, PGA < 0.5, prednisolone ≤5mg/day
∞ Compared to non-use of anti-malarials at current visit

* LLDAS; Lupus Low Disease Activity State; SLEDAI-2K≤4, PGA < 0.5, prednisolone ≤7.5mg/day)
# Clinical remission; clinical SLEDAI=0, PGA < 0.5, prednisolone ≤5mg/day
^ Complete remission; SLEDAI-2K=0, PGA < 0.5, prednisolone ≤5mg/day
α Includes MMF, CSA, AZA, LEF, MTX or tacrolimus


Disclosures: J. Cho, None; l. shen, None; M. Huq, None; R. Kandane-Rathnayake, None; V. Golder, None; W. Louthrenoo, None; Y. Chen, None; L. Hamijoyo, None; L. Fen, None; Y. Wu, None; L. Zamora, None; Z. Zhang, 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. Li, None; D. Basnayake, 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. Bae, None; F. Goldblatt, None; S. Oon, None; S. O'Neill, None; K. Gibson, Eli Lilly Pty Ltd; K. Ng, None; H. Law, None; N. Tugnet, None; S. Kumar, None; C. Tee, None; M. Tee, None; N. Ohkubo, 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; S. Navarra, Biogen, Astellas, Janssen, Novartis, Pfizer, Boehringer-Ingelheim, GlaxoSmithKline (GSK); C. Sing, None; 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; M. Nikpour, Janssen, AstraZeneca, GlaxoSmithKlein(GSK), Boehringer-Ingelheim, Bristol-Myers Squibb(BMS); A. Lateef, None.