Background/Purpose: Post-hoc analysis of two Phase III studies of belimumab¹ showed that an SRI(4) response is associated with clinically meaningful benefits, irrespective of treatment assignment. Confirmation of these findings in independent cohorts will enhance the acceptance of SRI(4) as a measure of clinically meaningful improvement. This analysis assessed global clinical benefit represented by an SRI(4) response.

Methods: Changes from baseline in clinical, laboratory, and patient-reported outcome measures at Day 365 were compared between SRI(4) responders (n=396) and non-responders (n=340) in the combined dataset of two Phase IIb studies evaluating sifalimumab and anifrolumab (MUSE) in moderate to severe SLE.

Results: Baseline demographics were similar between the studies. At Day 365, a greater percentage of responders than non-responders had ≥7-point reduction in SLE Disease Activity Index 2000 (SLEDAI-2K) and had their oral corticosteroid dose reduced to ≤7.5 mg/day (Table). Responders also had greater percentage changes from baseline in clinical SLEDAI scores, and greater improvements in Physician’s Global Assessment (PGA) score and number of SLEDAI-2K organ domains with improvement. British Isles Lupus Assessment Group (BILAG) “A” or “2B” flare rates were lower in SRI(4) responders. A larger percentage of responders with ≥8 swollen and ≥8 tender joints at baseline had ≥50% improvement in swollen and tender joint counts. In patients with moderate to severe skin disease at baseline, defined as Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) activity score ≥10, more responders had ≥50% improvement in CLASI. In patients with detectable anti–double-stranded DNA (anti-dsDNA) antibodies at baseline, responders had greater improvements in anti-dsDNA concentrations; however, in patients with low complement concentrations at baseline, the improvements in complement C3 and C4 concentrations were similar between responders and non-responders. Responders also had greater improvements in patient-reported outcomes: percentage change from baseline in Patient Global Assessment, and absolute change in Short Form 36 Health Survey (SF-36; Physical Component Summary, Mental Component Summary, Vitality) and Functional Assessment of Chronic Illness Therapy (FACIT)–Fatigue scores.

Conclusion: SRI(4) response in patients with moderate to severe SLE was associated with broad improvements in clinical and patient-reported outcomes. SRI(4) response in this analysis was driven by clinical components and confirm previous findings suggesting SRI(4) response is associated with global clinically important benefits. References: ¹Furie R, et al. Lupus Sci Med 2014;1:e000031. First presented at EULAR 2016.