The role of baseline BLyS levels and type 1 interferon-inducible gene signature status in determining belimumab response in systemic lupus erythematosus: a post hoc meta-analysis
| Autor: | Shaun M. Flint, Robert B Henderson, Christel Wilkinson, Beulah Ji, Roger A. Levy, Angela Jones-Leone, David M. Roth, Damon Bass, Mark Lennon |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
medicine.medical_specialty lcsh:Diseases of the musculoskeletal system B lymphocyte stimulator Placebo Antibodies Monoclonal Humanized Gastroenterology Severity of Illness Index 03 medical and health sciences 0302 clinical medicine Systemic lupus erythematosus Statistical significance Internal medicine B-Cell Activating Factor medicine Humans Lupus Erythematosus Systemic RNA Messenger B-cell activating factor Randomized Controlled Trials as Topic 030203 arthritis & rheumatology business.industry B cell activating factor Messenger RNA Hazard ratio Odds ratio Belimumab Confidence interval Rheumatology Treatment Outcome Interferon Type I Interferon Female lcsh:RC925-935 business 030215 immunology medicine.drug Research Article |
| Zdroj: | Arthritis Research & Therapy Arthritis Research & Therapy, Vol 22, Iss 1, Pp 1-11 (2020) |
| ISSN: | 1478-6362 1478-6354 |
| Popis: | Background Elevated B lymphocyte stimulator (BLyS) levels in patients with systemic lupus erythematosus (SLE) correlate positively with disease activity; BLyS expression is directly linked to interferon (IFN) pathway activation. This post hoc meta-analysis of BLISS-52 and BLISS-76 explored the relationship between baseline BLyS mRNA/protein levels and/or type 1 IFN-inducible gene signature (IFN-1) and responses to the BLyS-targeting monoclonal antibody belimumab in SLE. Methods In BLISS-52 and BLISS-76, patients with autoantibody-positive SLE and a SELENA-SLEDAI score ≥ 6 and receiving stable standard SLE therapy were randomised to intravenous belimumab 10 mg/kg or placebo, plus standard of care (SoC), for 52 or 76 weeks. For this post hoc meta-analysis, patients with an appropriate mRNA sample were stratified by BLyS mRNA expression (tertiles: high/medium/low; revised quantiles: high/low), IFN-1 mRNA expression (high/low) and BLyS protein level (high/low). Co-primary endpoints were correlation between baseline BLyS and IFN-1 mRNA levels and SLE Responder Index (SRI)4 response at week 52 within BLyS/IFN-1 subgroups. Secondary endpoints included time to first severe SELENA-SLEDAI Flare Index (SFI) flare. Results Of 554 patients included in this analysis, 281 had received belimumab and 273 had received placebo. Baseline BLyS and IFN-1 mRNA levels were highly correlated (Spearman’s rank correlation coefficient 0.7799; 95% confidence interval [CI] 0.7451, 0.8106; p p = 0.0153), high BLyS mRNA quantile (OR 1.58; 95% CI 1.02, 2.44; p = 0.0402), high IFN-1 mRNA (OR 1.58; 95% CI: 1.08, 2.31; p = 0.0186) and high BLyS protein (OR 3.57; 95% CI 1.63, 7.83; p = 0.0015) subgroups only. The risk of severe SFI flare was significantly lower with belimumab than placebo in the high BLyS mRNA quantile (hazard ratio [HR] 0.59; 95% CI 0.36, 0.97; p = 0.0371) and high BLyS protein (HR 0.39; 95% CI 0.19, 0.79; p = 0.0090) subgroups. Conclusions This post hoc meta-analysis demonstrated a tendency towards improved response to add-on intravenous belimumab 10 mg/kg versus SoC alone in patients with high baseline BLyS protein and IFN-1 mRNA levels and medium/high BLyS mRNA levels. |
| Databáze: | OpenAIRE |
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