Format

Send to

Choose Destination
Arthritis Rheumatol. 2018 Sep;70(9):1450-1458. doi: 10.1002/art.40522. Epub 2018 Aug 3.

Development and Validation of a Novel Evidence-Based Lupus Multivariable Outcome Score for Clinical Trials.

Author information

1
McGill University and the Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
2
University of Calgary, Calgary, Alberta, Canada, and Arthritis Research Canada, Richmond, British Columbia, Canada.
3
Northwestern University, Chicago, Illinois.
4
SDG, Cambridge, Massachusetts.
5
Stanford University School of Medicine, Palo Alto, California.
6
RILITE Research Institute, Charlottesville, Virginia.

Abstract

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 (LuMOS) and assessed its performance using data from 2 randomized controlled trials of belimumab in patients with SLE.

METHODS:

The LuMOS 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 LuMOS was assessed using an independent validation data set from the BLISS-52 trial.

RESULTS:

The LuMOS 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 LuMOS score. In all analyses of the BLISS-76 and BLISS-52 trial data sets, the mean LuMOS 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 LuMOS 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 LuMOS than with the SRI-4.

CONCLUSION:

The evidenced-based LuMOS 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 LuMOS may improve the efficiency and power of analyses in future lupus trials.

PMID:
29648686
DOI:
10.1002/art.40522
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center