POS0152 PREVALENCE AND OUTCOMES OF SEVERE REFRACTORY SYSTEMIC LUPUS ERYTHEMATOSUS (SLE): OBSERVATIONS FROM A MULTINATIONAL COHORT
Authors: R. Kandane-Rathnayake, W. Louthrenoo, C. S. Lau, L. Hamijoyo, J. Cho, A. Lateef, S. F. Luo, Y. J. Jan Wu, S. Navarra, L. Zamora, Z. LI, Y. H. Chen, S. Oon, M. Chan, S. Sockalingam, Y. Hao, Z. Zhang, S. C. Bae, J. Kikuchi, T. Takeuchi, Y. Katsumata, M. Harigai, D. Basnayake, F. Goldblatt, S. O ’neill, K. P. L. Ng, N. Tugnet, S. Kumar, A. Law Hui Nee, C. Tee, M. Tee, N. Ohkubo, A. Jullion, T. Shisha, Y. Tanaka, V. Golder, M. Nikpour, A. Hoi, E. Morand
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> A subset of patients with systemic lupus erythematosus (SLE) suffer serious manifestations and are relatively resistant to conventional treatments, such as combinations of glucocorticoids (GC) and immunosuppressive (IS) therapy. Clear definitions of severe refractory SLE (srSLE) are lacking, limiting its reporting in real-world data from observational cohorts or utility in trial enrolment. <h3>Objectives:</h3> We sought to evaluate a potential definition of srSLE by describing clinical characteristics and associated outcomes at 6- and 12-month time-points from the first visit with srSLE (index visit) in a large multi-national cohort. <h3>Methods:</h3> Data from a 13-country longitudinal SLE cohort (ACR/SLICC criteria), collected prospectively between 2013 and 2020 using standard templates were analysed. srSLE was defined if patients were in high disease activity status (HDAS; i.e. SLEDAI-2K ≥10) [1] despite combination GC and IS therapy at that visit (visit<sub><i>t</i>,</sub> defined as the index visit) and at the preceding visit (visit<sub><i>t-1</i></sub>). Subsequent visits were synchronised to the index visit to assess disease activity indicators (SLEDAI-2K, PGA, SELENA-SLEDAI Flare Index, ACR/SLICC Damage Index), medication use (GC, anti-malarials (AM) and IS) and treat-to-target (T2T) endpoints (LLDAS [2], DORIS remission [3] and steroid-free remission at 6-months (6m; 182±30 days) and 12-months (12m; 365±30 days). <h3>Results:</h3> 4,106 patients and 42,347 visits were examined. 578 (14%) patients had srSLE in 1,810 visits (Figure 1). Of these, 339 (59%) and 288 (50%) had follow-up data at 6m and 12m respectively. At the index visit, median [IQR] SLEDAI-2K and PGA of srSLE patients were 12 [10, 14] and 1.2 [0.8, 1.8] respectively, and 47% had organ damage. The median SLEDAI score at 6 and 12 months decreased to 6 [IQR4-10]. The median [IQR] GC dose (prednisolone equivalent) at the index visit was 10 [5, 20] mg/day, but reduced to 7.5mg [IQR: 5.0, 12.9] at 6m, and at 12m [IQR: 5.0, 10.0]. 14% and 20% of srSLE patients attained LLDAS at 6m and 12m, whereas only 8% and 12% attained DORIS remission at 6m and 12m, respectively. Less than 1% of srSLE patients achieved steroid free remission and the majority of patients remained on combination GC, AM and IS at both follow-up time points. 56% of patients had organ damage by 12 months (Figure 1). <h3>Conclusion:</h3> 1 in 7 patients with SLE in a longitudinal multicentre cohort experienced srSLE. Despite continuing combination conventional therapy, disease activity remained high and attainment of treat-to-target states was low. These findings support a proposed definition of srSLE and highlight the need for improved therapies for these patients, which can inform clinical guidelines and trial design. <h3>REFERENCES:</h3> [1] Koelmeyer R, Nim HT, Nikpour M, Sun YB, Kao A, Guenther O, et al. High disease activity status suggests more severe disease and damage accrual in systemic lupus erythematosus. Lupus science &amp; medicine. 2020 May; 7(1). [2] Golder V, Kandane-Rathnayake R, Huq M, Nim H, Louthrenoo W, Luo SF, et al. Lupus low disease activity state as a treatment endpoint for systemic lupus erythematosus: a prospective validation study. The Lancet Rheumatology. 2019; 1(2):e95–e102. [3] van Vollenhoven RF, Bertsias G, Doria A, Isenberg D, Morand E, Petri MA, et al. 2021 DORIS definition of remission in SLE: final recommendations from an international task force. Lupus science &amp; medicine. 2021 Nov; 8(1). <h3>Acknowledgements:</h3> We acknowledge the Asia Pacific Lupus Collaboration (APLC) patient cohort participants and the data collectors at all APLC sites. <h3>Disclosure of Interests:</h3> Rangi Kandane-Rathnayake GSK, Novartis (all institutional research grants), Worawit Louthrenoo: None declared, Chak Sing Lau: None declared, Laniyati Hamijoyo: None declared, Jiacai Cho: None declared, Aisha Lateef: None declared, Shue Fen Luo: None declared, Yeong-Jian Jan Wu: None declared, Sandra Navarra Astra-Zeneca, Boehringer Ingelheim, Glaxo Smith Kline, Pfizer, Astra Zeneca, Biogen, Boehringer Ingelheim, Aurinia, Biogen, Idorsia, Novartis, Leonid Zamora: None declared, Zhanguo Li: None declared, Yi-Hsing Chen: None declared, Shereen Oon: None declared, Madelynn Chan: None declared, Sargunan Sockalingam: None declared, Yanjie Hao: None declared, Zhuoli Zhang: None declared, Sang-Cheol Bae: None declared, Jun Kikuchi: None declared, Tsutomu Takeuchi Bristol-Myers Squibb, Eli Lilly Japan, Mitsubishi-Tanabe Pharma Corp., Sanofi K.K., Eli Lilly Japan, Astellas Pharma, Inc., Mitsubishi-Tanabe Pharma Corp., Shionogi &amp; Co., Ltd, Yasuhiro Katsumata Asahi Kasei Pharma, Astellas Pharma Inc., AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd., GlaxoSmithKline K.K., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Corporation, Pfizer Japan Inc., Sanofi K.K., Masayoshi Harigai AbbVie Japan GK, Ayumi Pharmaceutical Co., Boehringer Ingelheim Japan, Inc.,Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., GlaxoSmithKline K.K., Kissei Pharmaceutical Co., Ltd., Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd., and Teijin Pharma Ltd., AbbVie, Boehringer-ingelheim, Bristol Myers Squibb Co., Kissei Pharmaceutical Co.,Ltd. and Teijin Pharma., AbbVie Japan GK, Asahi Kasei Corp., Astellas Pharma Inc., Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Daiichi-Sankyo, Inc.,Eisai Co., Ltd., Kissei Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Nippon Kayaku Co., Ltd., Sekiui Medical, Shionogi &amp; Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and Teijin Pharma Ltd., Duminda Basnayake: None declared, Fiona Goldblatt: None declared, Sean O'Neill: None declared, Kristine Pek Ling Ng: None declared, Nicola Tugnet: None declared, Sunil Kumar: None declared, Annie Law Hui Nee: None declared, Cherica Tee: None declared, Michael Tee: None declared, Naoaki Ohkubo: None declared, Astrid Jullion Novartis, Novartis employee, Tamas Shisha Novartis, Novartis, Novartis, Yoshiya Tanaka Eli Lilly, AstraZeneca, Abbvie, Gilead, Chugai, Behringer-Ingelheim, GlaxoSmithKline, Eisai, Taisho, Bristol-Myers, Pfizer, Taiho, Mitsubishi-Tanabe, Eisai, Chugai, Taisho, Vera Golder On the advisory board for Abbvie and GSK, AstraZeneca, GSK, BMS, Janssen, and Merck Serono, Mandana Nikpour AstraZeneca, Boehringer Ingelheim, GSK, Janssen, AstraZeneca, Boehringer Ingelheim, GSK, Janssen, Boehringer Ingelheim, Janssen, Alberta Hoi: None declared, Eric Morand AstraZeneca, Merck, Gilead, Roche, EMD Serono, AstraZeneca, Biogen, Bristol Myers Squibb, Eli Lilly, Genentech, GlaxoSmithKline, Janssen, Novartis, AbbVie, Galapagos, IgM, AbbVie, Amgen, AstraZeneca, Biogen, BMS, Eli Lilly, EMD Serono, Genetech, GSK, Janssen, UCB (all institutional).