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Development and Validation of a Novel Evidence‐Based Lupus Multivariable Outcome Score for Clinical Trials
Author(s) -
Abrahamowicz Michal,
Esdaile John M.,
RamseyGoldman Rosalind,
Simon Lee S.,
Strand Vibeke,
Lipsky Peter E.
Publication year - 2018
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.40522
Subject(s) - medicine , belimumab , bliss , systemic lupus erythematosus , clinical trial , logistic regression , placebo , randomized controlled trial , prednisone , disease , immunology , pathology , alternative medicine , b cell , b cell activating factor , computer science , antibody , programming language
Objective Trials of new systemic lupus erythematosus ( SLE ) treatments are hampered by the lack of effective outcome measures. To address this, we developed a novel Lupus Multivariable Outcome Score (Lu MOS ) and assessed its performance using data from 2 randomized controlled trials of belimumab in patients with SLE . Methods The Lu MOS formula was developed by analyzing raw data from 2 pivotal trials, the Study of Belimumab in Subjects with SLE 52‐week ( BLISS ‐52) and 76‐week ( BLISS ‐76) trials, which are the basis for approval of belimumab. Using the BLISS ‐76 trial data as the learning data set, we carried out multivariable logistic regression analyses to optimize discrimination of outcomes between patients treated with 10 mg/kg belimumab and patients receiving placebo over the first 52 weeks of follow‐up. In addition, the performance of Lu MOS was assessed using an independent validation data set from the BLISS ‐52 trial. Results The Lu MOS model incorporated the following response criteria: a ≥4‐point reduction on the Safety of Estrogens in Lupus Erythematosus National Assessment version of the SLE Disease Activity Index, an increase in C4 levels, a decrease in anti–double‐stranded DNA titers, and changes in the British Isles Lupus Assessment Group scores for organ system manifestations (no worsening in renal components, and improvements in mucocutaneous components). A decrease in the prednisone dose and increase in C3 levels had very minor impacts on the total Lu MOS score. In all analyses of the BLISS ‐76 and BLISS ‐52 trial data sets, the mean Lu MOS scores were significantly higher ( P < 0.0001) in patients treated with 1 mg or 10 mg belimumab compared to placebo. In contrast to the performance of the SLE Responder Index 4 ( SRI ‐4), the Lu MOS revealed significant differences between the active treatment group (1 mg belimumab in the BLISS ‐76 cohort) and placebo group. The effect sizes were significantly much higher with the Lu MOS than with the SRI ‐4. Conclusion The evidenced‐based Lu MOS outcome scoring system, developed with data from the BLISS ‐76 trial of belimumab in patients with SLE and validated with data from the BLISS ‐52 trial, exhibits a superior capacity to discriminate responders from nonresponders when compared to the SRI ‐4. Use of the Lu MOS may improve the efficiency and power of analyses in future lupus trials.