POS0184 EFFICACY OF BIIB059 ON SKIN MANIFESTATIONS IN PARTICIPANTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) IN THE PHASE 2 LILAC STUDY (PART A)

Abstract

BackgroundSLE is a heterogeneous disease with diverse clinical presentations, and up to 70–80% of patients develop skin manifestations.1–3 In SLE, plasmacytoid dendritic cells (pDCs), a major source of Type I interferon (IFN), accumulate in the skin.4 Treatment with BIIB059, a humanized monoclonal antibody targeting blood dendritic cell antigen 2 (BDCA2) that is expressed on pDCs, leads to rapid internalization of BDCA2 from the surfaces of pDCs and inhibits the production of Type I IFNs, pro-inflammatory cytokines, and chemokines.5 Part A of the randomized, two-part, Phase 2 LILAC study (NCT02847598) enrolled participants with SLE and active skin and joint disease. The primary endpoint was met, with a greater reduction in total active joint count at Week 24 in the BIIB059 treatment group vs placebo (PBO), and more participants achieved a ≥50% improvement from baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index – Activity (CLASI-A) score with BIIB059 vs PBO.6ObjectivesTo further evaluate the effect of BIIB059 vs PBO in reducing skin disease activity, as measured by various CLASI-A response thresholds.MethodsAdults with an SLE diagnosis according to the revised ACR 1997 SLE classification criteria, with ≥4 tender and ≥4 swollen joints (28-joint assessment), active skin disease (as defined by the SLE Disease Activity Index 2000 [SLEDAI-2K]), and positive anti-nuclear antibodies and/or anti-double-stranded DNA antibodies, were enrolled. Participants were randomized to receive BIIB059 450 mg or PBO, administered subcutaneously every 4 weeks with an additional dose at Week 2. Improvements in skin disease were assessed in participants with baseline CLASI-A score ≥8. The proportion of participants achieving a ≥7-point reduction from baseline in CLASI-A score was assessed at Week 24, and CLASI-20, -50, -70, and -90 responses were assessed over time. Achievement of CLASI-A scores of 0–1 was also assessed at Week 24. These analyses used non-responder imputation with logistic regression, without correction for multiplicity. The proportions of participants achieving CLASI-A scores of 0–3 and with resolution of SLEDAI-2K skin rash at Week 24 were evaluated ad hoc in the same population. Non-responder imputation was applied to visits post treatment failure and treatment discontinuation. Improvement from baseline in British Isles Lupus Assessment Group index (BILAG-2004) A or B mucocutaneous domains was similarly assessed at Week 24. P-values were calculated based on the odds ratios (ORs) for BIIB059 compared with PBO.ResultsAt Week 24, a significantly greater proportion of participants receiving BIIB059 (n=39) vs PBO (n=38) had a ≥7-point reduction in CLASI-A score from baseline to Week 24 (56.4% vs 34.2%, OR [95% confidence interval {CI}] 2.71 [1.03, 7.17], P=0.044). Numerically greater proportions of participants receiving BIIB059 vs PBO achieved CLASI-50, CLASI-70, or CLASI-90 responses (Figure 1). Similarly, the proportion of participants who achieved CLASI-A scores of 0–1 was greater in the BIIB059 group vs PBO (25.6% vs 13.2%), as was the proportion who achieved CLASI-A scores of 0–3 (48.7% vs 28.9%). A greater proportion of BIIB059- vs PBO-treated participants had resolution of SLEDAI-2K skin rash at Week 24 (28.6% vs 10.7%), with similar findings seen in the BILAG-2004 mucocutaneous domain.ConclusionNumerically greater reductions in skin disease activity were consistently observed with BIIB059 treatment vs PBO in participants with SLE and active skin disease, supporting a potential benefit of BIIB059 treatment for skin manifestations in SLE.