Association of SLE Responder Index (SRI) Attainment and Long-term Clinical Outcomes

Kathryn Connelly¹, Rangi Kandane-Rathnayake¹, Alberta Hoi², Worawit Louthrenoo³, Laniyati Hamijoyo⁴, Jiacai Cho⁵, Aisha Lateef⁶, Shue-Fen Luo⁷, Yeong-Jian Wu⁸, C.S. Lau⁹, YI-HSING CHEN¹⁰, Sandra Navarra¹¹, Leonid Zamora¹¹, Zhanguo Li¹², Yuan An¹², Sargunan Sockalingam¹³, Yanjie Hao¹⁴, Zhuoli Zhang¹⁴, Madelynn Chan¹⁵, Yasuhiro Katsumata¹⁶, Masayoshi Harigai¹⁶, Shereen Oon¹⁷, Sang-Cheol Bae¹⁸, Sean O’Neill¹⁹, Kathryn Gibson¹⁹, Jun Kikuchi²⁰, B.M.D.B. Basnayake²¹, Tsutomu Takeuchi²², Kristine (Pek Ling) Ng²³, Fiona Goldblatt²⁴, Annie Law²⁵, Nicola Tugnet²⁶, Yoshiya Tanaka²⁷, Sunil Kumar²⁸, Michael Tee²⁹, Jin Yu Tan³⁰, Chetan Karyekar³¹, Mandana Nikpour³², Vera Golder¹ and Eric Morand³³, ¹Monash University, Clayton, Australia, ²Department of Rheumatology, Monash Health & Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, Australia, ³Maharaj Nakorn Chiangmai, Chiang Mai, Thailand, ⁴University of Padjadjaran, Bandung, Indonesia, ⁵National University Health System (NUHS), Singapore, Singapore, ⁶National University Hospital, Singapore, Singapore, ⁷Chang Gung Memorial Hospital, Taipei, Taiwan, ⁸Chang Gung Memorial Hospital, Taoyuan County, Taiwan, ⁹University of Hong Kong, Hong Kong, Hong Kong, ¹⁰Taichung Veterans General Hospital, Taichung, Taiwan (Republic of China), ¹¹University of Santo Tomas Hospital, Manila, Philippines, ¹²People's Hospital, Peking University Health Science Center, Beijing, China (People's Republic), ¹³University of Malaya, Kuala Lumpur, Malaysia, ¹⁴Peking University First Hospital, Beijing, China (People's Republic), ¹⁵Tan Tock Seng Hospital, Singapore, Singapore, ¹⁶Tokyo Women's Medical University School of Medicine, Tokyo, Japan, ¹⁷Melbourne Health, Parkville, Australia, ¹⁸Hanyang University Medical Center, Seoul, Republic of Korea, ¹⁹Liverpool Hospital, Sydney, Australia, ²⁰Keio University School of Medicine, Tokyo, Japan, ²¹Teaching (General) Hospital, Kandy, Sri Lanka, ²²Div. Rheumatology, Keio University, Tokyo, Japan, ²³North Shore Hospital, Auckland, New Zealand, ²⁴Flinders Medical Centre, Adelaide, Australia, ²⁵Singhealth, Singapore, Singapore, ²⁶Auckland District Health Board, Auckland, New Zealand, ²⁷University of Occupational and Environmental Health, Kitakyushu, Japan, ²⁸Counties Manukau Health, Auckland, New Zealand, ²⁹University of the Philippines, Quezon City, Philippines, ³⁰Janssen Asia Pacific, Singapore, Singapore, ³¹Janssen R&D, Spring House, PA, ³²University of Melbourne at St Vincent's Hospital, Melbourne, Australia, ³³School of Clinical Sciences at Monash Health, Monash University Faculty of Medicine, Nursing and Health Sciences, Monash Medical Centre Clayton, Melbourne, Australia

Meeting: ACR Convergence 2021

Keywords: longitudinal studies, Outcome measures, Response Criteria, Systemic lupus erythematosus (SLE)

Session Information

Date: Monday, November 8, 2021

Title: SLE – Diagnosis, Manifestations, & Outcomes Poster III: Outcomes (1257–1303)

Session Type: Poster Session C

Session Time: 8:30AM-10:30AM

Background/Purpose: The SLE Responder Index (SRI) is a composite responder definition employed as a clinical trial endpoint in SLE. Despite its widespread adoption, recent discrepant trial results have questioned its performance as an efficacy endpoint, and there is limited validation of the SRI against long-term clinical outcomes. The aim of this study was to investigate longitudinal associations of SRI attainment with key clinical outcomes.

Methods: We used data from a large multi-centre longitudinal SLE cohort. Eligible patients had active disease (SLEDAI-2K ≥6) at a visit designated as baseline. Attainment of a modified version of the SLE Responder Index (mSRI; excluding BILAG criteria) defined as a reduction in SLEDAI-2k ≥4 with no worsening in physician global assessment (PGA) ≥0.3 was determined at 1-year intervals from baseline (up to 5 years). The associations between mSRI attainment and a range of clinical outcomes (longitudinal disease activity, steroid use, flare, damage accrual, attainment of lupus low disease activity state (LLDAS (Golder 2019)), clinical remission on therapy (CROT (van Vollenhoven 2017)) and mortality) were determined using univariable linear and logistic regression.

Results: A total of 2,024 patients had an eligible baseline visit. Baseline characteristics are summarised in Table 1. mSRI response was attained by 55.5% of patients at 1 year, with similar rates (54-57%) at subsequent annual visits. Associations of mSRI response with clinical outcomes were similar at each of the annual time points; Table 2 presents results at years 1, 3 and 5 post baseline. Attainment of mSRI was associated with significantly lower disease activity over follow-up. Damage accrued in 9% of patients at 1 year and 32% by 5 years, with rates numerically lower in mSRI responders at all time points (significant at years 2 and 3). mSRI response was also significantly associated with attainment of LLDAS and clinical remission on therapy. Prednisolone doses at follow-up visits were consistently lower in the mSRI responder group, but time-adjusted mean dose had no significant differences. mSRI response was not associated with significant protection against flare. There were insufficient deaths for meaningful between-group comparison.

Conclusion: In a longitudinal cohort of SLE patients with baseline SLEDAI ≥6, attainment of a modified SRI responder index at annual visits up to 5 years was associated with clinical benefit including lower disease activity, reduced damage accrual and higher attainment of treat-to-target endpoints.

Table 1: Baseline characteristics (n=2024)

Table 2: Associations between mSRI attainment and clinical outcomes at follow up years 1, 3 and 5

Disclosures: K. Connelly, Janssen, 6; R. Kandane-Rathnayake, None; A. Hoi, AstraZeneca, 2, 5, Janssen, 6, Abbvie, 6; W. Louthrenoo, None; L. Hamijoyo, None; J. Cho, None; A. Lateef, None; S. Luo, None; Y. Wu, None; C. Lau, None; Y. CHEN, None; S. Navarra, Biogen, 2, Boehringer Ingelheim, 6, Pfizer, 6, Novartis, 6, Johnson & Johnson, 6; L. Zamora, None; Z. Li, None; Y. An, None; S. Sockalingam, None; Y. Hao, None; Z. Zhang, None; M. Chan, DKSH, 1, 6, Johnson & Johnson, 1, AbbVie, 12, EULAR Congress 2021 registration fee; Y. Katsumata, Glaxo-Smithkline K.K., 6, Sanofi K.K., 6, AstraZeneca K.K., 6, Chugai Pharmaceutical Co., Ltd., 6, Pfizer Japan Inc., 6, Astellas Pharma Inc., 6, Mitsubishi Tanabe Pharma Corporation, 6, Janssen Pharmaceutical K.K., 6; M. Harigai, None; S. Oon, Janssen, 6; S. Bae, None; S. O’Neill, None; K. Gibson, Eli Lilly, 3; J. Kikuchi, None; B. Basnayake, None; T. Takeuchi, Astellas Pharma, 2, 5, 6, Chugai Pharmaceutical, 2, 5, 6, Asahi Kasei Pharma, 5, Mitsubishi Tanabe, 2, 5, 6, AbbVie, 5, 6, Daiichi Sankyo, 5, 6, Eisai, 5, 6, Shionogi, 5, Takeda, 5, UCB Japan, 5, Eli Lilly Japan, 2, 6, AYUMI, 6, Bristol-Myers Squibb, 6, Gilead Sciences, Inc., 6, Novartis, 6, Pfizer Japan, 6, Sanofi, 6, Dainippon Sumitomo, 6; K. Ng, None; F. Goldblatt, None; A. Law, None; N. Tugnet, None; Y. Tanaka, Daiichi-Sankyo, 2, 5, 6, Eli Lilly, 6, Novartis, 6, YL Biologics, 6, Bristol-Myers Squibb, 6, Eisai, 5, 6, Chugai, 5, 6, AbbVie, 2, 5, 6, Astellas, 6, Pfizer, 6, Sanofi, 2, 6, Asahi-kasei, 5, 6, GSK, 2, 6, Mitsubishi-Tanabe, 5, 6, Gilead, 6, Janssen, 6, Takeda, 5, Ayumi, 2, Taisho, 2; S. Kumar, None; M. Tee, None; J. Tan, Janssen, a division of Johnson and Johnson Pte Ltd, 3; C. Karyekar, Janssen Global Services, LLC, 3, 11; M. Nikpour, None; V. Golder, None; E. Morand, Amgen, 2, AbbVie, 2, Biogen, 2, Bristol Myers Squibb, 2, 5, AstraZeneca, 2, 5, 6, Genentech, 2, Servier, 2, Capella Biosciences, 2, Eli Lilly, 5, 6, EMD Serono, 5, 6, Janssen, 2, 5, UCB, 2, GlaxoSmithKline, 2, 5.

To cite this abstract in AMA style:

Connelly K, Kandane-Rathnayake R, Hoi A, Louthrenoo W, Hamijoyo L, Cho J, Lateef A, Luo S, Wu Y, Lau C, CHEN Y, Navarra S, Zamora L, Li Z, An Y, Sockalingam S, Hao Y, Zhang Z, Chan M, Katsumata Y, Harigai M, Oon S, Bae S, O’Neill S, Gibson K, Kikuchi J, Basnayake B, Takeuchi T, Ng K, Goldblatt F, Law A, Tugnet N, Tanaka Y, Kumar S, Tee M, Tan J, Karyekar C, Nikpour M, Golder V, Morand E. Association of SLE Responder Index (SRI) Attainment and Long-term Clinical Outcomes [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 9). https://acrabstracts.org/abstract/association-of-sle-responder-index-sri-attainment-and-long-term-clinical-outcomes/. Accessed .

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