Associations of improvement in laboratory tests with clinical outcomes in patients with active systemic lupus erythematosus: a multinational longitudinal cohort study

Kathryn Connelly¹, Rangi Kandane-Rathnayake², Alberta Hoi², Worawit Louthrenoo³, Laniyati Hamijoyo⁴, Jiacai Cho⁵, Aisha Lateef⁵, Shue Fen Luo⁶, Yeong-Jian J Wu⁶, Zhanguo Li⁷, Sandra Navarra⁸, Leonid Zamora⁸, Sargunan Sockalingam⁹, Yanjie Hao¹⁰, Zhuoli Zhang¹⁰, Yasuhiro Katsumata¹¹, Masayoshi Harigai¹¹, Shereen Oon¹², Madelynn Chan¹³, Yi-Hsing Chen¹⁴, Sang-Cheol Bae¹⁵, Sean O'Neill¹⁶, Fiona Goldblatt¹⁷, Jun Kikuchi¹⁸, Tsutomu Takeuchi¹⁸, Kristine Pek Ling Ng¹⁹, Nicola Tugnet²⁰, B M D B Basnayake²¹, Naoaki Ohkubo²², Yoshiya Tanaka²², Chak Sing Lau²³, Mandana Nikpour¹², Vera Golder², Eric F Morand²; Asia-Pacific Lupus Collaboration

Affiliations

¹ School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, Australia. Electronic address: kathryn.connelly@monash.edu.
² School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, Australia.
³ Division of Rheumatology, Department of Internal Medicine, Chiang Mai University Hospital, Chiang Mai, Thailand.
⁴ Division of Rheumatology, Department of Internal Medicine, Padjadjaran University, Bandung, Indonesia.
⁵ Rheumatology Division, University Medical Cluster, National University Hospital, Singapore.
⁶ Department of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital, Taoyuan City, Taiwan.
⁷ Department of Rheumatology and Immunology, People's Hospital Peking University Health Science Center, Beijing, China.
⁸ Bone and Joint Center, University of Santo Tomas Hospital, Manila, Philippines.
⁹ Department of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
¹⁰ Department of Rheumatology and Immunology, Peking University First Hospital, Beijing, China.
¹¹ Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan.
¹² Department of Rheumatology, St Vincent's Hospital, Melbourne, VIC, Australia.
¹³ Department of Rheumatology, Allergy and Immunology, Tan Tock Seng Hospital, Singapore.
¹⁴ Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung City, Taiwan.
¹⁵ Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea.
¹⁶ Rheumatology Department, Liverpool Hospital, Liverpool, NSW, Australia.
¹⁷ Department of Rheumatology, Flinders Medical Centre and Royal Adelaide Hospital, Bedford Park, SA, Australia.
¹⁸ Division of Rheumatology, Department of Internal Medicine, Keio University, Tokyo, Japan.
¹⁹ Department of Medicine, North Shore Hospital, Auckland, New Zealand.
²⁰ Department of Rheumatology, Greenlane Clinical Centre, Auckland, New Zealand.
²¹ Division of Nephrology, Teaching Hospital Kandy, Kandy, Sri Lanka.
²² The First Department of Internal Medicine, University of Occupational and Environmental Health, Fukuoka, Japan.
²³ Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Hong Kong, Hong Kong Special Administrative Region, China.

PMID: 38261391
DOI: 10.1016/S2665-9913(22)00307-1

Associations of improvement in laboratory tests with clinical outcomes in patients with active systemic lupus erythematosus: a multinational longitudinal cohort study

Kathryn Connelly et al. Lancet Rheumatol. 2022 Dec.

. 2022 Dec;4(12):e831-e841.

doi: 10.1016/S2665-9913(22)00307-1. Epub 2022 Nov 7.

Authors

Affiliations

¹ School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, Australia. Electronic address: kathryn.connelly@monash.edu.
² School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, Australia.
³ Division of Rheumatology, Department of Internal Medicine, Chiang Mai University Hospital, Chiang Mai, Thailand.
⁴ Division of Rheumatology, Department of Internal Medicine, Padjadjaran University, Bandung, Indonesia.
⁵ Rheumatology Division, University Medical Cluster, National University Hospital, Singapore.
⁶ Department of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital, Taoyuan City, Taiwan.
⁷ Department of Rheumatology and Immunology, People's Hospital Peking University Health Science Center, Beijing, China.
⁸ Bone and Joint Center, University of Santo Tomas Hospital, Manila, Philippines.
⁹ Department of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
¹⁰ Department of Rheumatology and Immunology, Peking University First Hospital, Beijing, China.
¹¹ Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan.
¹² Department of Rheumatology, St Vincent's Hospital, Melbourne, VIC, Australia.
¹³ Department of Rheumatology, Allergy and Immunology, Tan Tock Seng Hospital, Singapore.
¹⁴ Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung City, Taiwan.
¹⁵ Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea.
¹⁶ Rheumatology Department, Liverpool Hospital, Liverpool, NSW, Australia.
¹⁷ Department of Rheumatology, Flinders Medical Centre and Royal Adelaide Hospital, Bedford Park, SA, Australia.
¹⁸ Division of Rheumatology, Department of Internal Medicine, Keio University, Tokyo, Japan.
¹⁹ Department of Medicine, North Shore Hospital, Auckland, New Zealand.
²⁰ Department of Rheumatology, Greenlane Clinical Centre, Auckland, New Zealand.
²¹ Division of Nephrology, Teaching Hospital Kandy, Kandy, Sri Lanka.
²² The First Department of Internal Medicine, University of Occupational and Environmental Health, Fukuoka, Japan.
²³ Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Hong Kong, Hong Kong Special Administrative Region, China.

PMID: 38261391
DOI: 10.1016/S2665-9913(22)00307-1

Abstract

Background: The selection and categorisation of laboratory tests in disease activity measures used within systemic lupus erythematosus (SLE) trial endpoints lack strong evidence. We aimed to determine whether longitudinal improvements in routinely measured laboratory tests are associated with measures of clinical improvement in patients with baseline active SLE.

Methods: We included patients from a multicentre longitudinal cohort (recruited between May 1, 2013, and Dec 31, 2019) with active SLE (SLEDAI-2K ≥6) coinciding with an abnormality in at least one of 13 routine laboratory tests, at a visit designated as baseline. At 12 months, we analysed associations between thresholds of improvement in individual laboratory test results, measured as continuous variables, and five clinical outcomes using logistic regression. Primary outcomes were damage accrual and lupus low disease activity state (LLDAS), and secondary outcomes were modified SLE responder index (mSRI), physician global assessment (PGA) improvement of at least 0·3, and flare.

Findings: We included 1525 patients (1415 [93%] women and 110 [7%] men, 1328 [87%] Asian ethnicity) in separate subsets for each laboratory test. The strongest associations with LLDAS and damage protection were seen with improvements in proteinuria (complete response: adjusted odds ratio [OR] 62·48, 95% CI 18·79-208·31 for LLDAS, OR 0·22, 95% CI 0·10-0·49 for damage accrual), albumin (complete response: adjusted OR 6·46, 95% CI 2·20-18·98 for LLDAS, OR 0·42, 95% CI 0·20-1·22 for damage accrual), haemoglobin (complete response: adjusted OR 1·97, 95% CI 1·09-3·53 for LLDAS, OR 0·33, 95% CI 0·15-0·71 for damage accrual), erythrocyte sedimentation rate (complete response: adjusted OR 1·71, 95% CI 1·10-2·67 for LLDAS, OR 0·53, 95% CI 0·30-0·94 for damage accrual), and platelets (complete response: adjusted OR 4·82, 95% CI 1·54-15·07 for LLDAS, OR 0·49, 95% CI 0·20-1·19 for damage accrual). Improvement in serological tests were mainly associated with PGA and mSRI. White cell and lymphocyte count improvements were least predictive.

Interpretation: Improvements in several routine laboratory tests correspond with clinical outcomes in SLE over 12 months. Tests with the strongest associations were discrepant with laboratory tests included in current trial endpoints, and associations were observed across a range of improvement thresholds including incomplete resolution. These findings suggest the need to revise the use of laboratory test results in SLE trial endpoints.

Funding: Abbvie.

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Conflict of interest statement

Declaration of interests KC reports grants from the National Health and Medical Research Council and Royal Australian College of Physicians, personal fees from AstraZeneca, and sponsorship from Janssen and Pfizer. AH reports grants from Merck Serono, AstraZeneca, Janssen, Bristol Myers Squibb and UCB, personal fees from Abbvie, Janssen, and GlaxoSmithKline, sponsorship from Janssen, and honorary treasurer and board participation for Australia Rheumatology Association. SN reports personal fees from Biogen, Boehringer Ingelheim, Janssen, Novartis, Pfizer, and GlaxoSmithKline, sponsorship from Pfizer, and advisory board participation for Biogen. YK reports personal fees from GlaxoSmithKline, AstraZeneca, Sanofi, Pfizer Japan, Janssen, Chugai, Asahi-Kasei, Astellas, and Mitsubishi Tanabe Pharma. MH reports grants from Chugai, and personal fees from GlaxoSmithKline, Chugai, and AstraZeneca. KPLN reports advisory board participation for Abbvie. TT reports grants from Astellas, Asahi-Kasei, Chugai, and Mitsubishe-Tanabe, and personal fees from Astellas and Chugai. YT reports grants from Asahi-Kasei, Abbvie, Chugai, Eisai, Takeda, Daiichi-Sankyo, and Boehringer-Ingelheim, and personal fees from Behringer-Ingelheim, Eli Lilly, Abbvie, Gilead, AstraZeneca, Bristol Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Pfizer, Mitsubishi-Tanabe, and GlaxoSmithKline. MN reports grants from Janssen, and personal fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Janssen and Pfizer. EFM reports grants from Janssen, Astra-Zeneca, Bristol Myers Squibb, Eli Lilly, EMD Serono, GlaxoSmithKline, Genentech, UCB, Amgen, Abbvie, and Biogen; personal fees from Amgen, AstraZeneca, Biogen, Bristol Myers Squibb, Capella, Eli Lilly, EMD Serono, Genentech, GlaxoSmithKline, Janssen, Neovacs, Novartis, Sanofi, Servier, UCB, Wolf, and Zenas; sponsorship from AstraZeneca; a patent application with Monash University; and a not-for-profit participation in Rare Voices of Australia. All other authors declare no competing interests.

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Associations of improvement in laboratory tests with clinical outcomes in patients with active systemic lupus erythematosus: a multinational longitudinal cohort study

Affiliations

Associations of improvement in laboratory tests with clinical outcomes in patients with active systemic lupus erythematosus: a multinational longitudinal cohort study

Authors

Affiliations

Abstract

Conflict of interest statement

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Medical

Research Materials