Improvements in Abnormal Laboratory Tests Are Associated with Clinical Outcomes in Patients with Active Systemic Lupus Erythematosus

Kathryn Connelly¹, Rangi Kandane-Rathnayake¹, Alberta Hoi², Worawit Louthrenoo³, Laniyati Hamijoyo⁴, Jiacai Cho⁵, Aisha Lateef⁶, Shue-Fen Luo⁷, Yeong-Jian Wu⁸, Zhanguo Li⁹, Yuan An⁹, Sandra Navarra¹⁰, Leonid Zamora¹⁰, Sargunan Sockalingam¹¹, Yanjie Hao¹², Zhuoli Zhang¹², Yasuhiro Katsumata¹³, Masayoshi Harigai¹³, Shereen Oon¹⁴, Madelynn Chan¹⁵, YI-HSING CHEN¹⁶, Sang-Cheol Bae¹⁷, Sean O’Neill¹⁸, Kathryn Gibson¹⁸, Fiona Goldblatt¹⁹, Jun Kikuchi²⁰, Tsutomu Takeuchi²¹, Kristine (Pek Ling) Ng²², Nicola Tugnet²³, B.M.D.B. Basnayake²⁴, Yoshiya Tanaka²⁵, C.S. Lau²⁶, Mandana Nikpour²⁷, Vera Golder¹ and Eric Morand²⁸, 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, ⁹People's Hospital, Peking University Health Science Center, Beijing, China (People's Republic), ¹⁰University of Santo Tomas Hospital, Manila, Philippines, ¹¹University of Malaya, Kuala Lumpur, Malaysia, ¹²Peking University First Hospital, Beijing, China (People's Republic), ¹³Tokyo Women's Medical University School of Medicine, Tokyo, Japan, ¹⁴Melbourne Health, Parkville, Australia, ¹⁵Tan Tock Seng Hospital, Singapore, Singapore, ¹⁶Taichung Veterans General Hospital, Taichung, Taiwan (Republic of China), ¹⁷Hanyang University Medical Center, Seoul, Republic of Korea, ¹⁸Liverpool Hospital, Sydney, Australia, ¹⁹Flinders Medical Centre, Adelaide, Australia, ²⁰Keio University School of Medicine, Tokyo, Japan, ²¹Div. Rheumatology, Keio University, Tokyo, Japan, ²²North Shore Hospital, Auckland, New Zealand, ²³Auckland District Health Board, Auckland, New Zealand, ²⁴Teaching (General) Hospital, Kandy, Sri Lanka, ²⁵University of Occupational and Environmental Health, Kitakyushu, Japan, ²⁶University of Hong Kong, Hong Kong, Hong Kong, ²⁷University of Melbourne at St Vincent's Hospital, Melbourne, Australia, ²⁸School 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, 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: Laboratory tests are routine in the management of SLE. In clinical trial endpoints, data from laboratory tests contribute to responder status, but this is captured using discrete thresholds rather than continuous data. We investigated whether the trajectory of abnormal laboratory tests in patients with active SLE, measured as continuous data, corresponds with conventional measures of clinical improvement.

Methods: We used clinical and laboratory data from a large multinational prospectively followed longitudinal cohort. Eligible patients had active disease (SLEDAI-2K ≥6), and at least one abnormal routine laboratory test (haemoglobin, white cell count, lymphocytes, platelets, ESR, albumin, C3, C4, anti-dsDNA, and urine protein, red cells or white cells), at a visit designated as baseline. At 12 months thereafter, for each laboratory test we classified improvement from individual patient baselines as complete response (CR; 100% improvement i.e. restoration to normal range), partial response (PR; ≥ 20-< 100% improvement) or no response (NR; < 20% improvement)) and assessed associations with a range of improvement outcomes: modified SLE responder index (omitting BILAG criteria) (mSRI4), physician global assessment (PGA) improvement ≥ 0.3, attainment of lupus low disease activity state (LLDAS (Golder, 2019)), SLE flare index (SFI) and SLICC/ACR damage index accrual (SDI increase >0), using logistic regression.

Results: 1,525 patients were included, with separate subsets for each individual abnormal laboratory test. Most patients were female (93%), Asian (88%) and had established SLE. Associations (odds ratios, 95% confidence intervals and significance) of laboratory variable CR and PR with clinical outcomes at 12 months are shown in Figure 1. Improvement in proteinuria, albumin, haemoglobin, ESR and platelets had the strongest associations with clinical improvement measures, including increased odds of LLDAS attainment and protection against damage accrual. In contrast, serology was associated only with the less stringent outcomes of PGA improvement and mSRI4. White cell count and lymphocytes had the weakest associations with improvement measures. Although CR had stronger associations, PR of certain laboratory tests also conferred benefit.

Conclusion: Improvements in abnormal laboratory tests were predictive of clinical outcomes at 12 months, with a discrepancy between tests currently incorporated in clinical trial endpoints, such as serology, and those with the strongest associations with clinical outcomes. Associations with improved clinical outcomes were associated with improvement thresholds less stringent than complete resolution for some tests. The selection, weighting and threshold-based use of laboratory tests in lupus trial endpoints should be revised.

Figure 1: Associations of partial and complete improvement in abnormal laboratory tests between baseline and 12 months, and corresponding clinical improvement outcomes.

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; Z. Li, None; Y. An, None; S. Navarra, Biogen, 2, Boehringer Ingelheim, 6, Pfizer, 6, Novartis, 6, Johnson & Johnson, 6; L. Zamora, None; S. Sockalingam, None; Y. Hao, None; Z. Zhang, None; 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; M. Chan, DKSH, 1, 6, Johnson & Johnson, 1, AbbVie, 12, EULAR Congress 2021 registration fee; Y. CHEN, None; S. Bae, None; S. O’Neill, None; K. Gibson, Eli Lilly, 3; F. Goldblatt, None; J. Kikuchi, 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; N. Tugnet, None; B. Basnayake, 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; C. Lau, None; 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, Li Z, An Y, Navarra S, Zamora L, Sockalingam S, Hao Y, Zhang Z, Katsumata Y, Harigai M, Oon S, Chan M, CHEN Y, Bae S, O’Neill S, Gibson K, Goldblatt F, Kikuchi J, Takeuchi T, Ng K, Tugnet N, Basnayake B, Tanaka Y, Lau C, Nikpour M, Golder V, Morand E. Improvements in Abnormal Laboratory Tests Are Associated with Clinical Outcomes in Patients with Active Systemic Lupus Erythematosus [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 9). https://acrabstracts.org/abstract/improvements-in-abnormal-laboratory-tests-are-associated-with-clinical-outcomes-in-patients-with-active-systemic-lupus-erythematosus/. Accessed .

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