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

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 0middot3, 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] 62middot48, 95% CI 18middot79-208middot31 for LLDAS, OR 0middot22, 95% CI 0middot10-0middot49 for damage accrual), albumin (complete response: adjusted OR 6middot46, 95% CI 2middot20-18middot98 for LLDAS, OR 0middot42, 95% CI 0middot20-1middot22 for damage accrual), haemoglobin (complete response: adjusted OR 1middot97, 95% CI 1middot09-3middot53 for LLDAS, OR 0middot33, 95% CI 0middot15-0middot71 for damage accrual), erythrocyte sedimentation rate (complete response: adjusted OR 1middot71, 95% CI 1middot10-2middot67 for LLDAS, OR 0middot53, 95% CI 0middot30-0middot94 for damage accrual), and platelets (complete response: adjusted OR 4middot82, 95% CI 1middot54-15middot07 for LLDAS, OR 0middot49, 95% CI 0middot20-1middot19 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. Copyright (c) 2022 Published by Elsevier Ltd. All rights reserved.

Automated summary

This study aimed to determine the association between improvements in routinely measured laboratory tests and clinical improvement in patients with active SLE. The study found that improvements in proteinuria, albumin, hemoglobin, erythrocyte sedimentation rate, and platelets were most strongly associated with disease activity and damage protection, while improvements in serological tests were mainly associated with physician global assessment and modified SLE responder index. These findings suggest the need to revise the use of laboratory test results in SLE trial endpoints.