Dataset Information

External Validation of the Lupus Multivariable Outcome Score for Systemic Lupus Erythematosus Trials.

ABSTRACT:

Objective

Development of new systemic lupus erythematosus (SLE) treatments requires an effective responder index. Toward this end, we have recently developed a new Lupus Multivariable Outcome Score (LuMOS) to optimize discrimination between actively treated patients and those on placebo. We now report on external validation of LuMOS in two independent clinical trials.

Methods

Validation was performed with the Illuminate data sets that evaluated tabalumab (TB) in SLE. To accommodate laboratory results assessed on different platforms, we developed a standardized LuMOS 2.0 model that uses z score transformations of biomarker values. For validation, we calculated LuMOS 2.0 scores at week 52 for all participants. Effect size (ES), with 95% confidence intervals (CIs), compared the ability of LuMOS and the SLE Responder Index-5 (SRI-5) to discriminate between outcomes in patients randomized to TB dosage and outcomes in those randomized to a placebo.

Results

Mean LuMOS 2.0 scores were significantly higher (P < 0.0001) for the TB groups than the placebo group, including the Illuminate-1 trial, in which the SRI-5 did not identify significant treatment effects. For both TB groups in both trials, LuMOS 2.0-based ES indicated moderately strong treatment effects (>0.4) in contrast to weak SRI-5 effects (<0.25). For monthly TB, LuMOS 2.0-based ES were 0.44 (95% CI: 0.30-0.59) and 0.54 (95% CI: 0.39-0.68) for the Illuminate-1 and Illuminate-2 trials versus corresponding SRI-5-based ES of 0.13 (95% CI: -0.02 to +0.27) and 0.15 (95% CI: 0.01-0.30).

Conclusion

LuMOS 2.0 detected significantly greater treatment effects compared with the SRI-5 in the Illuminate trials. Additional validation of LuMOS 2.0 in trials of non-B cell-directed therapies will be necessary to document its universality as an outcome measure.

SUBMITTER: Abrahamowicz M

PROVIDER: S-EPMC9555192 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Publications

External Validation of the Lupus Multivariable Outcome Score for Systemic Lupus Erythematosus Trials.

Abrahamowicz Michal M Abrahamowicz Maria Izabela MI Lipsky Peter E PE

ACR open rheumatology 20220812 10

<h4>Objective</h4>Development of new systemic lupus erythematosus (SLE) treatments requires an effective responder index. Toward this end, we have recently developed a new Lupus Multivariable Outcome Score (LuMOS) to optimize discrimination between actively treated patients and those on placebo. We now report on external validation of LuMOS in two independent clinical trials.<h4>Methods</h4>Validation was performed with the Illuminate data sets that evaluated tabalumab (TB) in SLE. To accommodat ...[more]

PMID: 35962577

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Project description:IntroductionSystemic lupus erythematosus (SLE) has been associated with an increased risk of cardiovascular (CV) disease. Recently, the Systematic Coronary Risk Assessment (SCORE), a well-known CV risk algorithm, has been updated to a new predictive model (SCORE2). This new algorithm improves the identification of individuals at high risk of developing CV disease across Europe. Since carotid atherosclerosis is a predictor of future CV events and CV death, our objective was to compare the predictive capacity of SCORE2 versus SCORE for the presence of subclinical carotid atherosclerosis in patients with SLE.MethodsTwo hundred and thirty-five individuals over 40 years of age diagnosed with SLE were consecutively recruited in this cross-sectional study. SCORE and SCORE2 were calculated. The relationship of SCORE and SCORE2 with each other, and with the presence of subclinical carotid atherosclerosis (both carotid plaque and carotid intima media thickness -cIMT-), was studied.ResultsSCORE2 and SCORE did not correlate with each other (Spearman's Rho = 0.125, p = 0.065). Although SCORE did not correlate with cIMT (Spearman's Rho = -0.022, p = 0.75), the correlation of SCORE2 with cIMT was statistically significant (Spearman's Rho = 0.367, p < 0.001). Similarly, SCORE did not show significant discrimination for the presence of carotid plaque [AUC = 0.521 (95% CI = 0.443-0.600)], while SCORE2 did [AUC = 0.720 (95% CI = 0.656-0.785)]. The difference between AUCs was found to be statistically significant (p < 0.001), thus showing that the prediction capacity of SCORE2 was significantly higher than that of SCORE.ConclusionIn SLE patients, the ability of SCORE2 to predict the presence of subclinical atherosclerosis is higher than that of SCORE. According to our results, SCORE2, rather than SCORE, should be used in the CV risk stratification of patients with SLE. Prospective studies are needed to confirm these findings.

Dataset Information

External Validation of the Lupus Multivariable Outcome Score for Systemic Lupus Erythematosus Trials.

Objective

Methods

Results

Conclusion

Publications

External Validation of the Lupus Multivariable Outcome Score for Systemic Lupus Erythematosus Trials.

Similar Datasets

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