Novel evidence-based systemic lupus erythematosus responder index.
OBJECTIVE
To describe a new systemic lupus erythematosus (SLE) responder index (SRI) based on a belimumab phase II SLE trial and demonstrate its potential utility in SLE clinical trials.


METHODS
Data from a randomized, double-blind, placebo-controlled study in 449 patients of 3 doses of belimumab (1, 4, 10 mg/kg) or placebo plus standard of care therapy (SOC) over a 56-week period were analyzed. The Safety of Estrogens in Lupus Erythematosus: National Assessment (SELENA) version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and British Isles Lupus Assessment Group (BILAG) SLE disease activity instruments, the Short Form 36 health survey, and biomarker analyses were used to create a novel SRI. Response to treatment in a subset of 321 serologically active SLE patients (antinuclear antibodies >/=1:80 and/or anti-double-stranded DNA antibodies >/=30 IU/ml) at baseline was retrospectively evaluated using the SRI.


RESULTS
SRI response is defined as 1) a >/=4-point reduction in SELENA-SLEDAI score, 2) no new BILAG A or no more than 1 new BILAG B domain score, and 3) no deterioration from baseline in the physician's global assessment by >/=0.3 points. In serologically active patients, the addition of belimumab to SOC resulted in a response in 46% of patients at week 52 compared with 29% of the placebo patients (P = 0.006). SRI responses were independent of baseline autoantibody subtype.


CONCLUSIONS
This evidence-based evaluation of a large randomized, placebo-controlled trial in SLE resulted in the ability to define a robust responder index based on improvement in disease activity without worsening the overall condition or the development of significant disease activity in new organ systems.
Furie
Richard A
RA
North Shore-Long Island Jewish Health System, Lake Success, New York, USA. furie@nshs.edu
Petri
Michelle A
MA
Wallace
Daniel J
DJ
Ginzler
Ellen M
EM
Merrill
Joan T
JT
Stohl
William
W
Chatham
W Winn
WW
Strand
Vibeke
V
Weinstein
Arthur
A
Chevrier
Marc R
MR
Zhong
Z John
ZJ
Freimuth
William W
WW
D000328:Adult; D000888:Antibodies, Anti-Idiotypic / Q000097:blood; D000974:Antibodies, Antinuclear / Q000097:blood; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D017322:Clinical Trials, Phase II as Topic; D004247:DNA / Q000276:immunology; D023381:Endpoint Determination; D019317:Evidence-Based Medicine; D005260:Female; D006305:Health Status Indicators; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D012720:Severity of Illness Index; D016896:Treatment Outcome
D000888:Antibodies, Anti-Idiotypic; D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C511911:belimumab; D004247:DNA