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Elevated BLyS levels in patients with systemic lupus erythematosus: Associated factors and responses to belimumab.
Lupus 2016; 25(4):346-54L

Abstract

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.

Authors+Show Affiliations

Research and Development, GlaxoSmithKline, Philadelphia, PA, USA David.A.Roth@gsk.com.Research and Development, GlaxoSmithKline, Research Triangle Park, NC, USA.Research and Development, GlaxoSmithKline, Research Triangle Park, NC, USA.Research and Development, GlaxoSmithKline, Research Triangle Park, NC, USA.Research and Development, GlaxoSmithKline, Philadelphia, PA, USA.Research and Development, GlaxoSmithKline, Philadelphia, PA, USA.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26385220

Citation

Roth, D A., et al. "Elevated BLyS Levels in Patients With Systemic Lupus Erythematosus: Associated Factors and Responses to Belimumab." Lupus, vol. 25, no. 4, 2016, pp. 346-54.
Roth DA, Thompson A, Tang Y, et al. Elevated BLyS levels in patients with systemic lupus erythematosus: Associated factors and responses to belimumab. Lupus. 2016;25(4):346-54.
Roth, D. A., Thompson, A., Tang, Y., Hammer, A. E., Molta, C. T., & Gordon, D. (2016). Elevated BLyS levels in patients with systemic lupus erythematosus: Associated factors and responses to belimumab. Lupus, 25(4), pp. 346-54. doi:10.1177/0961203315604909.
Roth DA, et al. Elevated BLyS Levels in Patients With Systemic Lupus Erythematosus: Associated Factors and Responses to Belimumab. Lupus. 2016;25(4):346-54. PubMed PMID: 26385220.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Elevated BLyS levels in patients with systemic lupus erythematosus: Associated factors and responses to belimumab. AU - Roth,D A, AU - Thompson,A, AU - Tang,Y, AU - Hammer,A E, AU - Molta,C T, AU - Gordon,D, Y1 - 2015/09/18/ PY - 2015/03/26/received PY - 2015/08/18/accepted PY - 2015/9/20/entrez PY - 2015/9/20/pubmed PY - 2016/12/15/medline KW - BLISS trials KW - BLyS KW - belimumab KW - regression analysis KW - systemic lupus erythematosus SP - 346 EP - 54 JF - Lupus JO - Lupus VL - 25 IS - 4 N2 - 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. SN - 1477-0962 UR - https://www.unboundmedicine.com/medline/citation/26385220/Elevated_BLyS_levels_in_patients_with_systemic_lupus_erythematosus:_Associated_factors_and_responses_to_belimumab_ L2 - http://journals.sagepub.com/doi/full/10.1177/0961203315604909?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -