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.

Belimumab: targeted therapy for lupus

“…2 new BILAG B organ domain scores and no worsening in PGA (< 0.3-point increase) (all scores compared with baseline). 23 BLISS-52 trial was conducted in 90 centres in 13 countries (primarily in Asia, South America and Eastern Europe) to assess the efficacy, safety and tolerability of belimumab with standard of care in seropositive SLE patients. 6 The study population included patients with active disease (score !…”

“…20 This exploratory analysis formed the basis for the development of the SLE Responder Index (SRI), a robust responder index that reflects improvement in disease activity using a global scoring system without concomitant worsening of the disease in any organ system. 23 This SRI was evaluated as the primary efficacy endpoint at 52 weeks for two large phase III trials. 6,7 …”

BAFF/BLyS inhibitors: A new prospect for treatment of systemic lupus erythematosus

“…The SRI had not been previously used in any other clinical trial for the treatment of SLE; this careful planning may explain, in part, why this trial did attain the primary endpoints. The SRI defines a disease response that is a reduction from baseline of at least four points on the ''Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index'' (SELENA-SLEDAI), with no clinically significant worsening of the British Isles Lupus Assessment Group (BILAG) index (no new BILAG A organ domain score indicating severe lupus disease activity and no more than one new BILAG B organ domain score, indicating moderate disease activity), and no worsening of the Physician's Global Assessment (indicated by an increase of 0.30 points above baseline) (31). This effectively means that the SRI is based on improvement of disease activity, without deterioration of the symptoms or wellbeing of the individual, and without development of new symptoms in previously unaffected organs.…”

Global versus organ‐specific outcome measures in systemic lupus erythematosus: Comment on the articles by Furie et al, Nikpour et al, Wallace et al, Burgos et al, and Ramos‐Casals et al

“…A recent issue of Arthritis Care & Research featured a series of valuable articles that all confronted, from different perspectives, the problem of measuring disease activity in systemic lupus erythematosus (SLE) (1)(2)(3)(4)(5). Despite very different messages otherwise, the authors of all of these papers either assume or argue that composite global indices of disease activity comprise a plausible goal and should serve as the primary, or only, outcome analyzed and reported in trials.…”

“…In their article, Furie et al are, of course, correct to note, "In other diseases where manifestations are heterogeneous, combined responder instruments have been used to assess disease activity (1)." However, the American College of Rheumatology 20% (ACR20) improvement criteria in rheumatoid arthritis (RA) is a particularly inappropriate example and could be used to support the opposite position (7).…”