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 of belimumab in two serologically distinct high disease activity subgroups of patients with systemic lupus erythematosus: post-hoc analysis of data from the phase III programme

2021 ◽  
Vol 8 (1) ◽  
pp. e000459
Author(s):  
Toni Maslen ◽  
Ian N Bruce ◽  
David D'Cruz ◽  
Mihaela Ianosev ◽  
Damon L Bass ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
High Disease Activity ◽  
Phase Iii ◽  
Systemic Lupus ◽  
Post Hoc Analysis ◽  
Link Type ◽  
Intravenous Treatment ◽  
Post Hoc

ObjectiveTo assess the appropriateness of expanded serological activity eligibility criteria for belimumab use in the UK systemic lupus erythematosus (SLE) population (and possibly other countries), which includes patients with either anti-double-stranded DNA (anti-dsDNA) positivity or hypocomplementaemia rather than both criteria.MethodsThis post-hoc analysis used data from three randomised, double-blind, placebo-controlled phase III belimumab trials: BLISS-52 (BEL110752; NCT00424476), BLISS-76 (BEL110751; NCT00410384) and BLISS-SC (BEL112341; NCT01484496). Patients with SLE were stratified by high disease activity (HDA): HDA1, Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI) score ≥10, low complement and positive anti-dsDNA; and HDA2, SELENA-SLEDAI ≥10 and either low complement or positive anti-dsDNA.ResultsThis analysis included 660 HDA1 patients (n=396 on intravenous treatment; n=264 on subcutaneous treatment) and 969 HDA2 patients (n=532 on intravenous treatment; n=437 on subcutaneous treatment). Significant improvements were observed at week 52 with belimumab versus placebo, irrespective of subgroups or drug formulations, in SLE Responder Index (SRI) 4 response (OR (95% CI): HDA1 intravenous 2.7 (1.8 to 4.1); HDA2 intravenous 2.3 (1.61 to 3.26); HDA1 subcutaneous 2.2 (1.22 to 3.85); HDA2 subcutaneous 1.8 (1.17 to 2.74)); proportion of patients achieving ≥4-point reduction in SELENA-SLEDAI score (OR (95% CI): HDA1 intravenous 2.6 (1.7 to 3.9); HDA2 intravenous 2.1 (1.49 to 3.03); HDA1 subcutaneous 2.3 (1.30 to 4.14); HDA2 subcutaneous 1.9 (1.21 to 2.84)); patients with no worsening in Physician Global Assessment (OR (95% CI): HDA1 intravenous 2.0 (1.3 to 3.1); HDA2 intravenous 1.7 (1.17 to 2.45); HDA1 subcutaneous 2.3 (1.18 to 4.40); HDA2 subcutaneous 1.8 (1.11 to 2.92)); and risk of severe flares (HR (95% CI): HDA1 intravenous 0.6 (0.37 to 0.81); HDA2 intravenous 0.6 (0.43 to 0.86); HDA1 subcutaneous 0.52 (0.30 to 0.92); HDA2 subcutaneous 0.59 (0.37 to 0.94)).ConclusionBroadening the HDA population to include either low complement or positive anti-dsDNA, rather than both, would enable more UK patients to receive SLE treatment and experience improved clinical outcomes.

Systemic Lupus Erythematosus Disease Activity Index 2000 Responder Index-50 Enhances the Ability of SLE Responder Index to Identify Responders in Clinical Trials

2011 ◽  
Vol 38 (11) ◽  
pp. 2395-2399 ◽  
Author(s):  
ZAHI TOUMA ◽  
DAFNA D. GLADMAN ◽  
DOMINIQUE IBAÑEZ ◽  
SHAHRZAD TAGHAVI-ZADEH ◽  
MURRAY B. UROWITZ
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Clinical Trials ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Activity Index ◽  
Disease Activity Index ◽  
Systemic Lupus ◽  
Original Definition ◽  
Definition Of

Objective.To evaluate the performance of the Systemic Lupus Erythematosus (SLE) Responder Index (SRI) when the SLE Disease Activity Index 2000 (SLEDAI-2K) is substituted with SLEDAI-2K Responder Index-50 (SRI-50), a valid and reliable index of disease activity improvement. Also, to determine whether the SRI-50 will enhance the ability of SRI in detecting responders.Methods.Our study was conducted on patients who attended the Lupus Clinic from September 2009 to September 2010. SLEDAI-2K, SRI-50, the British Isles Lupus Assessment Group measure, and the Physician’s Global Assessment were determined initially and at followup. SRI was determined at the followup visit according to its original definition using the SLEDAI-2K score and by substituting SLEDAI-2K with SRI-50.Results.A total of 117 patients with SLEDAI-2K ≥ 4 at baseline were studied. Patients had 1 followup visit over a 3-month period. Twenty-nine percent of patients met the original definition of SRI and 35% of patients met the definition of SRI when SLEDAI-2K was substituted with SRI-50. The use of SRI-50 allowed determination of significant improvement in 7 additional patients. This improvement could not be discerned with the use of SLEDAI-2K as a component of SRI. At followup visits that showed improvement, SRI-50 scores decreased to a greater extent than SLEDAI-2K scores (p < 0.0001).Conclusion.SRI-50 enhances the ability of SRI to identify patients with clinically important improvement in disease activity. SRI-50 was superior to SLEDAI-2K in detecting partial clinical improvement, ≥ 50%, between visits. These properties of the SRI-50 enable it to be used as an independent outcome measure of improvement or as a component of SRI in clinical trials.

scholarly journals Lupus Low Disease Activity State (LLDAS) attainment discriminates responders in a systemic lupus erythematosus trial: post-hoc analysis of the Phase IIb MUSE trial of anifrolumab

2018 ◽  
Vol 77 (5) ◽  
pp. 706-713 ◽  
Author(s):  
Eric F Morand ◽  
Teodora Trasieva ◽  
Anna Berglind ◽  
Gabor G Illei ◽  
Raj Tummala
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Activity Index ◽  
Controlled Trial ◽  
Systemic Lupus ◽  
Low Disease Activity ◽  
Link Type ◽  
Activity State ◽  
Post Hoc

ObjectivesIn a post-hoc analysis, we aimed to validate the Lupus Low Disease Activity State (LLDAS) definition as an endpoint in an systemic lupus erythematosus (SLE) Phase IIb randomised controlled trial (RCT) (MUSE [NCT01438489]) and then utilize LLDAS to discriminate between anifrolumab and placebo.MethodsPatients received intravenous placebo (n=102) or anifrolumab (300 mg, n=99; 1,000 mg, n=104) Q4W plus standard of care for 48 weeks. LLDAS attainment (SLE Disease Activity Index 2000 ≤4 without major organ activity, no new disease activity, Physician’s Global Assessment ≤1, prednisolone ≤7.5 mg/d and standard immunosuppressant dosage tolerance) was assessed. Associations with endpoints and LLDAS attainment differences between treatments were explored.ResultsLLDAS attainment at Week 52 was associated with SLE Responder Index 4 (SRI[4]) and British Isles Lupus Assessment Group–based Composite Lupus Assessment (BICLA) (74/85[87%] and 62/84[74%] were also SRI[4] and BICLA responders, respectively; both nominal p<0.001). Only 74/159 (47%) of SRI(4) and 62/121 (51%) of BICLA responders reached LLDAS.Anifrolumab-treated patients achieved earlier LLDAS, and more spent at least half their observed time in LLDAS (OR vs. placebo; 300 mg: 3.04, 95% CI 1.34 to 6.92, nominal p=0.008; 1,000 mg: 2.17, 95% CI 0.93 to 5.03, nominal p=0.072) vs placebo-treated patients. At Week 52, 17/102 (17%), 39/99 (39%) and 29/104 (28%) of patients on placebo, anifrolumab 300 and 1,000 mg, respectively, attained LLDAS (OR vs. placebo; 300 mg: 3.41, 95% CI 1.73 to 6.76, p<0.001; 1,000 mg: 2.03, 95% CI 1.01 to 4.07, nominal p=0.046).ConclusionsLLDAS attainment represents a clinically meaningful SLE outcome measure, and anifrolumab is associated with more patients who met LLDAS criteria versus placebo. These data support LLDAS as an SLE RCT endpoint.Trial registration numberNCT1438489; Post-results.

Development and Assessment of Users’ Satisfaction with the Systemic Lupus Erythematosus Disease Activity Index 2000 Responder Index-50 Website

2012 ◽  
Vol 40 (1) ◽  
pp. 34-39 ◽  
Author(s):  
ZAHI TOUMA ◽  
DAFNA D. GLADMAN ◽  
ANNE MacKINNON ◽  
SIMON CARETTE ◽  
MAHMOUD ABU-SHAKRA ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Clinical Trials ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Online Survey ◽  
Activity Index ◽  
Disease Activity Index ◽  
Second Phase ◽  
Systemic Lupus Erythematosus Disease ◽  
Systemic Lupus

Objective.To describe the development of the Systemic Lupus Erythematosus Disease Activity Index 2000 Responder Index-50 (S2K RI-50) Website (www.s2k-ri-50.com) and to assess satisfaction with its training and examination modules among rheumatologists and rheumatology fellows.Methods.The development of the Website occurred in 3 phases. The first was a deployment phase that consisted of preparing the site map along with its content. The content included the S2K RI-50 training manual, the tests and corresponding question bank, and the online adaptive training module, along with the extensive site testing. The second phase included the participation of rheumatologists and trainees who completed the Website modules. The third was a quality assurance phase in which an online survey was developed to determine the satisfaction level of its users. Further modifications were implemented per participants’ recommendations.Results.The site has been online since it was registered in September 2010. Fourteen rheumatologists and rheumatology trainees from different centers reviewed and completed the material contained in the Website. The survey revealed acceptance among rheumatologists for the Website’s content, design, and presentation. The Website was rated as user-friendly and useful in familiarizing investigators with the S2K RI-50. After completion of the training and examination modules, participants reported a suitable level of preparation to implement the S2K RI-50 in clinical trials and research settings in a timely manner.Conclusion.The Website includes training and examination modules that familiarize rheumatologists with the S2K RI-50 and assesses their competence to use the index. This prepares them for the use of the S2K RI-50 in clinical trials and research settings.

Lupus Low Disease Activity State (LLDAS) discriminates responders in the BLISS-52 and BLISS-76 phase III trials of belimumab in systemic lupus erythematosus

2019 ◽  
Vol 78 (5) ◽  
pp. 629-633 ◽  
Author(s):  
Shereen Oon ◽  
Molla Huq ◽  
Vera Golder ◽  
Pei Xuan Ong ◽  
Eric F Morand ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Phase Iii ◽  
Systemic Lupus ◽  
Low Disease Activity ◽  
Phase Iii Trials ◽  
The Difference ◽  
Activity State ◽  
Post Hoc

ObjectiveWe evaluated the discriminant capacity of the Lupus Low Disease Activity State (LLDAS) in post-hoc analysis of data from the BLISS-52 and BLISS-76 trials of belimumab in systemic lupus erythematosus (SLE).MethodsLLDAS attainment, discrimination between belimumab and placebo arms, and the effects in subgroups with high disease activity at recruitment were evaluated at week 52 using appropriate descriptive statistics, χ2 test and logistic regression.ResultsAt week 52, for belimumab 10 mg/kg, 17.0% and 19.3% of patients who achieved a Systemic Lupus Erythematosus Responder Index-4 also attained LLDAS in BLISS-52 and BLISS-76, respectively. Significantly more patients attained LLDAS on belimumab 10 mg/kg compared with placebo (12.5% vs 5.8%, OR 2.32, p=0.02 for BLISS-52; 14.4% vs 7.8%, OR 1.98, p=0.04 for BLISS-76). In a subgroup analysis, the difference in week 52 LLDAS attainment between belimumab 10 mg/kg and placebo was greater in patients who had higher disease activity at baseline, compared with the overall group.ConclusionsLLDAS was able to discriminate belimumab 10 mg/kg from placebo in the BLISS-52 and BLISS-76 trials. Our findings support the validity of LLDAS as an outcome measure in SLE 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).

Definitions of remission in systemic lupus erythematosus: a post-hoc analysis of two randomised clinical trials

2019 ◽  
Vol 1 (3) ◽  
pp. e163-e173 ◽  
Author(s):  
Ioannis Parodis ◽  
Sharzad Emamikia ◽  
Alvaro Gomez ◽  
Cidem Gentline ◽  
Elizabeth V Arkema ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Clinical Trials ◽  
Lupus Erythematosus ◽  
Randomised Clinical Trials ◽  
Systemic Lupus ◽  
Post Hoc Analysis ◽  
Post Hoc

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.

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