Novel evidence-based systemic lupus erythematosus responder index

Abstract

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.

Conclusion: 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.

Trial registration: ClinicalTrials.gov NCT00071487.

Figures

Figure 1. Belimumab effect on SELENA-SLEDAI score at week 52 in serologically active patients (N=321)

(A) Percent change in SELENA-SLEDAI from baseline over time. (B) Absolute changes from baseline in SELENA-SLEDAI score at week 52. (C) Percentage of patients with ≥4-point reduction in SELENA-SLEDAI score. a Statistically significant better response with belimumab all active vs placebo (P=0.04). b Statistically significant better response with belimumab all active vs placebo (P<0.05).

Figure 2. Belimumab effect on PGA and SF-36 scores at week 52 in serologically active patients (N=321)

(A) Percent change in PGA. (B) Absolute point change in SF-36 PCS. a Statistically significant better response with belimumab all active vs placebo (P<0.05).

Figure 3. Belimumab effect on BILAG domain scores at week 52 (new A or B scores)

Percent of serologically active patients with new 1A or 1B BILAG organ domain scores at week 52. a Statistically significant better response with belimumab all active vs placebo (P<0.05).

Figure 4. (A) SLE Responder Index over 52 weeks in serologically active patients (N=321). (B) Response rate at week 52 in belimumab-treated patients with different autoantibody subtypes at baseline

a Statistically significant better response with belimumab all active vs placebo (P=0.006).