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Elevated BLyS levels in patients with systemic lupus erythematosus: Associated factors and responses to belimumab #MMPMID26385220
Roth DA; Thompson A; Tang Y; Hammer AE; Molta CT; Gordon D
Lupus 2016[Apr]; 25 (4): 346-54 PMID26385220show ga
Introduction: Patients with systemic lupus erythematosus (SLE) with B-lymphocyte stimulator (BLyS) levels???2?ng/mL are at increased risk of flare. A regression analysis was undertaken to identify routine clinical measures that correlate with BLyS???2?ng/mL. Efficacy and safety of belimumab 10?mg/kg were examined in patients with BLyS???2?ng/mL and 2?ng/mL. Methods: Data from BLISS-52 and -76 (N?=?1684) were pooled post hoc. A univariate logistic regression was employed to identify factors predictive of baseline BLyS???2?ng/mL. Factors significant at the 0.05 level then entered a stepwise logistic regression as covariates. Efficacy endpoints included SLE responder index (SRI), ??4-point reduction in Safety of Estrogens in Lupus National Assessment?Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) and risk of severe flare over 52 weeks. Adverse events (AEs) were analyzed for each treatment arm and BLyS subgroup. Results: Baseline predictors of BLyS???2?ng/mL included positive anti-Smith (??15 U/mL), low complement (C) 3 (900?mg/L), anti-double-stranded DNA (anti-dsDNA) 80?200 and ??200?IU/mL, immunosuppressant usage, proteinuria, elevated C-reactive protein (CRP), and low total lymphocyte count for all patients. Belimumab 10?mg/kg led to significantly greater SRI responses over 52 weeks versus placebo in both BLyS subgroups, though treatment differences were numerically greater at Week 52 in the BLyS???2?ng/mL group (24.1%, p?0.0001) compared with BLyS?2?ng/mL (8.2%, p?=?0.0158). Results were similar for???4-point reduction in SELENA-SLEDAI. Risk of severe flare over 52 weeks was significantly reduced with belimumab 10?mg/kg versus placebo in the BLyS???2?ng/mL group (p?=?0.0002). AEs were similar across treatment arms and BLyS subgroups. Conclusions: Positive anti-Smith, low C3, anti-dsDNA???80?IU/mL, immunosuppressant usage, proteinuria, elevated CRP, and low total lymphocyte count were predictors of BLyS???2?ng/mL. Monitoring these factors could identify patients with BLyS???2?ng/mL who are at risk of flare.