scholarly journals A pivotal phase III, randomised, placebo-controlled study of belimumab in patients with systemic lupus erythematosus located in China, Japan and South Korea

2018 ◽  
Vol 77 (3) ◽  
pp. 355-363 ◽  
Author(s):  
Fengchun Zhang ◽  
Sang-Cheol Bae ◽  
Damon Bass ◽  
Myron Chu ◽  
Sally Egginton ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
South Korea ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Response Rate ◽  
Phase Iii ◽  
Controlled Study ◽  
Systemic Lupus ◽  
North East ◽  
Point Reduction

BackgroundIntravenous belimumab plus standard of care (SoC) is approved in the USA and Europe for treatment of active, autoantibody-positive systemic lupus erythematosus (SLE).MethodsThis phase III, multicentre, randomised, double-blind, placebo-controlled study (BEL113750; NCT01345253) was conducted in 49 centres across China, Japan and South Korea (May 2011–September 2015). Patients with SLE were randomised 2:1 to intravenous belimumab 10 mg/kg or placebo, plus SoC, every 4 weeks until Week 48. The primary endpoint was the SLE Responder Index (SRI) 4 response rate at Week 52. Secondary endpoints were the percentage of patients with ≥4 point reduction in Safety of Oestrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI), SRI7, time to first severe flare and number of days prednisone (or equivalent) dose ≤7.5 mg/day and/or reduced by 50% from baseline. Safety was assessed.ResultsThe modified intent-to-treat population included 677 patients (belimumab n=451, placebo n=226). At Week 52, the SRI4 response rate was higher with belimumab versus placebo (53.8% vs 40.1%; OR: 1.99 (95% CI: 1.40, 2.82; P=0.0001)). The percentages of patients with a ≥4 point reduction in SELENA-SLEDAI and an SRI7 response were significantly greater for belimumab versus placebo. Patients in the belimumab group had a 50% lower risk of experiencing a severe flare than those receiving placebo (P=0.0004). In patients with baseline prednisone dose >7.5 mg/day, there was a significant reduction in steroid use favouring belimumab (P=0.0228). The incidence of adverse events was similar between groups.ConclusionsIn patients with SLE from North East Asia, belimumab significantly improved disease activity, while reducing prednisone use, with no new safety issues.

scholarly journals Clinical response beyond the Systemic Lupus Erythematosus Responder Index: post-hoc analysis of the BLISS-SC study

2018 ◽  
Vol 5 (1) ◽  
pp. e000288 ◽  
Author(s):  
Ronald F van Vollenhoven ◽  
William Stohl ◽  
Richard A Furie ◽  
Norma Lynn Fox ◽  
James G Groark ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Clinical Trials ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Activity Index ◽  
Phase Iii ◽  
Controlled Study ◽  
Systemic Lupus ◽  
Post Hoc Analysis ◽  
Post Hoc

ObjectiveThe Systemic Lupus Erythematosus (SLE) Responder Index (SRI), developed as a primary outcome measure for use in clinical trials, captures improvement in SLE disease activity without concomitant worsening in disease manifestations. This study investigated the relationships between the SRI and clinical/laboratory correlates of SRI response in patients with SLE.MethodsThis was a post-hoc analysis of the phase III, double-blind, placebo-controlled study of subcutaneous BeLimumab in Subjects with Systemic lupus erythematosus - SubCutaneous (BLISS-SC). Patients were randomised to weekly belimumab 200 mg subcutaneously or placebo, plus standard SLE therapy. Changes from baseline to week 52 in clinical and laboratory parameters were compared among SRI responders and non-responders, irrespective of the treatment received.ResultsSRI responders (n=475) had significantly better (p<0.0001) outcomes compared with non-responders (n=358), including (by definition) higher proportions achieving ≥4-point improvement in Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (100.0% vs 2.0%), no worsening in British Isles Lupus Assessment Group (BILAG; 0 new BILAG A or ≤1 new BILAG B score; 100.0 % vs 50.3%) and no worsening (<0.3-point increase) in Physician’s Global Assessment score (100.0% vs 49.7%). Among patients receiving >7.5  mg/day corticosteroids at baseline, significantly more SRI responders had reductions in prednisone dose to ≤7.5 mg/day than non-responders. SRI responders reported lower flare rates and improvements in serological markers and Functional Assessment of Chronic Illness Therapy-Fatigue score than non-responders.ConclusionSRI response is associated with improvements in clinical and laboratory measures, strengthening its value as a clinically meaningful primary endpoint in clinical trials.

scholarly journals Efficacy and safety of belimumab in paediatric and adult patients with systemic lupus erythematosus: an across-study comparison

RMD Open ◽  
2021 ◽  
Vol 7 (3) ◽  
pp. e001747
Author(s):  
Hermine I Brunner ◽  
Carlos Abud-Mendoza ◽  
Masaaki Mori ◽  
Clarissa A Pilkington ◽  
Reema Syed ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Response Rate ◽  
Activity Index ◽  
Adult Patients ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Systemic Lupus ◽  
Link Type

ObjectiveTo assess the efficacy and safety of belimumab in paediatric versus adult patients with systemic lupus erythematosus (SLE).MethodsWe performed across-study comparisons of patients with active SLE who received belimumab or placebo, plus standard therapy, in PLUTO (paediatric phase II) and BLISS-52, BLISS-76, BLISS-NEA and EMBRACE (adult phase III). Analysed efficacy data included Week 52 SLE Responder Index (SRI)-4 response rate (EMBRACE: SRI with modified Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) proteinuria scoring (SRI-S2K)); SRI-4 response rate (EMBRACE: SRI-S2K) according to baseline disease activity indicators (Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) score; anti-dsDNA/C3/C4 levels); Week 52 SRI-6 response rate; and time to first severe flare (SELENA-SLEDAI Flare Index) over 52 weeks. Safety data were compared for all aforementioned studies along with adult LBSL02 (phase II) and BLISS-SC (phase III).ResultsSRI-4 response rates were similar across the paediatric and adult studies; more belimumab-treated patients achieved SRI-4 responses versus placebo (PLUTO: 52.8% vs 43.6%; BLISS-52: 57.6% vs 43.6%; BLISS-76: 43.2% vs 33.8%; BLISS-NEA: 53.8% vs 40.1%; EMBRACE: 48.7% vs 41.6%). Across all studies, SRI-4 response rates were generally greater in patients with baseline SELENA-SLEDAI scores ≥10 than in patients with baseline SELENA-SLEDAI scores ≤9. A similar proportion of belimumab-treated patients achieved SRI-6 across all studies (PLUTO: 41.2%; BLISS-52: 46.2%; BLISS-76: 33.1%; BLISS-NEA: 43.9%; EMBRACE: 37.5%). Belimumab reduced the risk of severe flare versus placebo in all studies. The incidence of adverse events was similar across all studies.ConclusionsThese analyses demonstrate consistent efficacy and safety of belimumab plus standard therapy across paediatric and adult patients with SLE.Trial registration numbersPLUTO (NCT01649765); BLISS-52 (NCT00424476); BLISS-76 (NCT00410384); BLISS-NEA (NCT01345253); EMBRACE (NCT01632241); BLISS-SC (NCT01484496); and LBSL02 (NCT00071487).

scholarly journals No Increase in Rate and Severity of Flares During Pregnancy and Post-Partum Period in Pregnant Patients with Systemic Lupus Erythematosus. A Sex, Age and Disease Duration Matched Controlled Study

2020 ◽  
Author(s):  
Worawit Louthrenoo ◽  
Thananant Trongkamolthum ◽  
Nuntana Kasitatnon ◽  
Antika Wongthanee
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Disease Duration ◽  
Post Partum ◽  
Age At Diagnosis ◽  
Controlled Study ◽  
Control Group ◽  
Systemic Lupus ◽  
Post Partum Period

Abstract Background: Flares in pregnant patients with systemic lupus erythematosus (SLE) have shown conflicting results. This study aimed to determine the disease activity, and rate and severity of flares in pregnant SLE patients compared with the non-pregnant SLE controls. Methods: The medical records of pregnant patients in the SLE cohort were identified. Controls were non-pregnant female SLE patients who were matched for age at diagnosis and disease duration prior to conception. Disease activity was determined by mSLEDAI-2K. The definition and severity of flares followed the SELANA-SLEDAI Flare Index. The disease activity was measured from 6 months prior to conception (-6M) until termination of pregnancy or delivery.Results: Ninety pregnancies occurred from 77 patients, of whom 36.67% had active disease at the time of conception. The pregnancy group was slightly, but significantly, younger than the control group at diagnosis (21.63 ± 5.89 years vs. 24.05 ± 7.27 years, p = 0.015). The SLE disease activity (mSLEDAI-2K) score was comparable in both groups from -6M to the post-partum period, with that in the control group being slightly but significantly higher than that in the pregnancy group at conception (3.57 ± 4.28 vs. 1.91 ± 3.44, p = 0.003). Of the 90 pregnancies, the overall incidence of flares in both groups was similar during pregnancy (39 vs. 26, p = 0.070). There also was no difference in the incidence of flare during each trimester, with 19 vs.7 flares among 90 pregnancies (p = 0.588) in the 1st, 12 vs. 12 among 82 (p = 0.682) in the 2nd, and 6 vs. 7 among 71 (p = 0.266) in the 3rd trimester. The incidence of flare during the post-partum period also was similar (42 vs. 30 flares among 90 pregnancies, p = 0.091). There was no difference in the severity of flare in each trimester, overall flare during pregnancy or post-partum flare. Conclusions: This study found no difference in flare rate or severity of flares between pregnant SLE patients and non-pregnant SLE controls, who were matched by sex, age at diagnosis and disease duration prior to pregnancy.

scholarly journals Sifalimumab, an anti-interferon-α monoclonal antibody, in moderate to severe systemic lupus erythematosus: a randomised, double-blind, placebo-controlled study

2016 ◽  
Vol 75 (11) ◽  
pp. 1909-1916 ◽  
Author(s):  
Munther Khamashta ◽  
Joan T Merrill ◽  
Victoria P Werth ◽  
Richard Furie ◽  
Kenneth Kalunian ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Cutaneous Lupus Erythematosus ◽  
Controlled Study ◽  
Interferon Α ◽  
Systemic Lupus ◽  
Double Blind ◽  
Double Blind Placebo ◽  
End Point

ObjectivesThe efficacy and safety of sifalimumab were assessed in a phase IIb, randomised, double-blind, placebo-controlled study (NCT01283139) of adults with moderate to severe active systemic lupus erythematosus (SLE).Methods431 patients were randomised and received monthly intravenous sifalimumab (200 mg, 600 mg or 1200 mg) or placebo in addition to standard-of-care medications. Patients were stratified by disease activity, interferon gene-signature test (high vs low based on the expression of four genes) and geographical region. The primary efficacy end point was the percentage of patients achieving an SLE responder index response at week 52.ResultsCompared with placebo, a greater percentage of patients who received sifalimumab (all dosages) met the primary end point (placebo: 45.4%; 200 mg: 58.3%; 600 mg: 56.5%; 1200 mg 59.8%). Other improvements were seen in Cutaneous Lupus Erythematosus Disease Area and Severity Index score (200 mg and 1200 mg monthly), Physician's Global Assessment (600 mg and 1200 mg monthly), British Isles Lupus Assessment Group-based Composite Lupus Assessment (1200 mg monthly), 4-point reductions in the SLE Disease Activity Index−2000 score and reductions in counts of swollen joints and tender joints. Serious adverse events occurred in 17.6% of patients on placebo and 18.3% of patients on sifalimumab. Herpes zoster infections were more frequent with sifalimumab treatment.ConclusionsSifalimumab is a promising treatment for adults with SLE. Improvement was consistent across various clinical end points, including global and organ-specific measures of disease activity.Trial registration numberNCT01283139; Results.

The efficacy of antimalarials in systemic lupus erythematosus

Lupus ◽  
1996 ◽  
Vol 5 (1_suppl) ◽  
pp. 23-27 ◽  
Author(s):  
V Nayak ◽  
Jm Esdaile
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Adjunctive Therapy ◽  
Severe Disease ◽  
Controlled Study ◽  
Systemic Lupus ◽  
Moderate Disease ◽  
Randomized Discontinuation Trial ◽  
Moderate Disease Activity

The use of antimalarial drugs to treat systemic lupus erythematosus (SLE) is receiving increased attention. A retrospective controlled study suggested that antimalarials were useful in suppressing disease activity in SLE. A randomized discontinuation trial of hydroxychloroquine sulphate supported the clinical belief that antimalarials are of benefit in SLE of mild to moderate disease activity and might have a role as adjunctive therapy to protect against more severe relapses of SLE. A randomized trial of the ability of hydroxychloroquine sulphate to suppress articular manifestations of SLE demonstrated no consistent statistically significant benefit, although the sample size was small. Anecdotal reports and the experience of expert clinicians have suggested a corticosteroid sparing role for antimalarials, although no controlled study has been conducted to specifically address this hypothesis. Thus, the evidence favors a role for antimalarials in suppressing mild to moderate disease activity in SLE and possibly in preventing severe disease exacerbations. Their role as corticosteroid sparing agents in SLE is widely believed, but unproven.

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