Dataset Information

Response to belimumab among patients with systemic lupus erythematosus in clinical practice settings: 24-month results from the OBSErve study in the USA.

ABSTRACT: To examine disease activity and clinical outcomes, and describe overall patterns of systemic lupus erythematosus (SLE) care in patients who received belimumab in a real-world clinical setting.This observational cohort study was conducted in US clinical practices. Rheumatologists (n=92) identified adults with SLE who had received ?8 infusions of belimumab plus standard of care (SoC). Physicians assessed disease outcomes at 6-month intervals using patient medical charts, for up to 24?months. The primary outcome was physician-assessed change in SLE disease. Other outcomes included change in steroid use, laboratory tests and healthcare resource utilisation (HCRU).Of 501 patients (intent-to-treat population (ITT)), 446 were female, mean age was 43.3?years and 98% had moderate/severe disease activity at baseline (first dose of belimumab). Data for 277 patients who completed 24?months of belimumab treatment were available. Among the ITT, a ?50% improvement in overall clinical response between baseline and month 6 was reported for 48.7% of patients; continued improvement was seen at all subsequent 6-month intervals relative to the previous timepoint. The percentage of patients with moderate/severe disease also decreased at each timepoint. At baseline, 77.0% of patients received steroids at a mean (SD) prednisone equivalent dose of 19.9 (14.39) mg/day, which decreased to 8.4 (7.35) mg/day at month 6 and 6.1 (9.31) mg/day at month 24. Abnormal laboratory values typically associated with SLE also demonstrated improvements at month 6, which continued through 24?months. HCRU decreased over the duration of the study.Patients with SLE who received belimumab plus SoC for up to 24?months demonstrated improvements in disease severity and laboratory values and a reduction in steroid use and HCRU as early as month 6. Improvements continued through 24?months, providing evidence of reduced disease activity among patients taking belimumab in real-world clinical practice.

SUBMITTER: Collins CE

PROVIDER: S-EPMC4716417 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Response to belimumab among patients with systemic lupus erythematosus in clinical practice settings: 24-month results from the OBSErve study in the USA.

Collins C E CE Dall'Era M M Kan H H Macahilig C C Molta C C Koscielny V V Chang D J DJ

Lupus science & medicine 20160111 1

<h4>Objective</h4>To examine disease activity and clinical outcomes, and describe overall patterns of systemic lupus erythematosus (SLE) care in patients who received belimumab in a real-world clinical setting.<h4>Methods</h4>This observational cohort study was conducted in US clinical practices. Rheumatologists (n=92) identified adults with SLE who had received ≥8 infusions of belimumab plus standard of care (SoC). Physicians assessed disease outcomes at 6-month intervals using patient medical ...[more]

PMID: 26835146

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Project description:IntroductionThe real-world effectiveness of belimumab for systemic lupus erythematosus (SLE) in six countries was evaluated in the OBSErve program. The aim of this post hoc analysis (GSK study 206351) was to pool individual patient OBSErve data to further evaluate the effectiveness of belimumab in a large sample of patients with SLE.MethodsOBSErve (Argentina, Canada, Germany, Spain, Switzerland, and the USA) enrolled adults ≥ 18 years of age with SLE, who were prescribed belimumab as part of standard therapy (index: date of belimumab initiation). Endpoints (month 6 vs. index) included physician-assessed overall clinical response to belimumab in the overall population (primary) and high disease activity subgroups (secondary; patients with a SLEDAI-2K/SELENA-SLEDAI score ≥ 10 or patients with high anti-dsDNA or low complement at index); other secondary endpoints included changes in glucocorticosteroid (GCS) use and changes in disease activity. Factors associated with physician-assessed overall clinical response were also evaluated.ResultsIn total, 830 patients were included in the overall population (mean [standard deviation (SD)] age: 41.9 [12.57] years; female: 89.3%; 60.4% from the USA). Nearly half (48.1%) of belimumab-treated patients experienced a ≥ 50% physician-assessed improvement in their overall manifestations, and 13% achieved a near normalization of their condition (equal to ≥ 80% improvement). Initiating belimumab while on high-dose (> 7.5 mg/day) GCS use was associated with ≥ 50% clinical improvement at month 6 (OR: 1.9, p = 0.003). Most (78.1%; n = 518/663) patients were able to reduce or discontinue their oral GCS dose after 6 months of belimumab, with a mean (SD) change of - 8.5 (10.74) mg/day prednisone-equivalent. The mean (SD) change from belimumab initiation in disease activity score (SLEDAI-2K/SELENA-SLEDAI) was - 5.7 (4.5; n = 344).ConclusionsBelimumab improves clinical manifestations of SLE and is associated with GCS dose reductions in a real-world clinical setting, supporting the real-world effectiveness of belimumab for SLE.

Project description:Background and objectiveIntravenous (IV) belimumab is the first treatment approved for children ≥5 years of age with active autoantibody-positive systemic lupus erythematosus (SLE) in the USA, Europe, and Japan. Pharmacokinetic data for belimumab were collected from several clinical trials in Chinese and non-Chinese adults and non-Chinese pediatric patients with SLE. This study aimed to predict the belimumab dose-exposure relationship to Chinese pediatric patients with SLE, as part of the belimumab registration process for this population in China, using a population PK modeling approach.MethodsAn initial linear two-compartment population pharmacokinetic model was built using data from adults only, and considering and adjusting for the covariates age, body weight, body mass index, fat-free mass, race, baseline albumin and immunoglobulin G levels. The model was used to study possible ethnic differences between Chinese and non-Chinese adults and to predict pediatric pharmacokinetic data in a study of non-Chinese pediatric patients (PLUTO study; NCT01649765). The predicted data were compared with the observed data from PLUTO. The model was then updated with pediatric data from PLUTO to predict steady-state belimumab exposure in Chinese pediatric patients with SLE receiving belimumab 10 mg/kg IV every 4 weeks.ResultsThe dataset comprised 9650 sampled concentration values from 1783 patients. The pharmacokinetics of belimumab were adequately described by the final model using all adult and pediatric data with the estimated typical clearance of 238 ml/day in adult and pediatric patients and steady-state volume of distribution of 4915 ml in adults. Between-patient variability was modest (coefficients of variation: 26.1% for clearance; 8.9% and 28.5%, respectively, for volumes of distribution of the central and peripheral compartments). Six covariates were identified that influenced pharmacokinetics: age, fat-free mass, an indicator of North East Asian race, baseline albumin, immunoglobulin G, and an early study indicator (two early phase I and phase II belimumab studies: LBSL01 and LBSL02). The analysis showed no apparent difference in steady-state exposure between Chinese and non-Chinese populations and between pediatric and adult populations receiving belimumab 10 mg/kg IV.ConclusionsIn Chinese pediatric patients with SLE, belimumab 10 mg/kg IV every 4 weeks is expected to have exposure similar to that in Chinese adults and non-Chinese pediatric patients with SLE, supporting the use of this regimen in Chinese pediatric patients with SLE.Clinical trial registration numbersNCT01649765, NCT00657007, NCT00071487, NCT01345253, NCT01516450, NCT00410384, NCT00424476, NCT02880852, NCT01583530.

Project description:IntroductionBelimumab is a recombinant human monoclonal antibody that binds to soluble B-lymphocyte stimulator and inhibits its biological activity. Since receiving approvals for the treatment of systemic lupus erythematosus (SLE), several observational studies have investigated the effectiveness of belimumab in the real-world setting. This study reports a systematic review and meta-analysis of the literature to evaluate the real-world effectiveness of belimumab for the treatment of SLE.MethodsA literature search following PRISMA Guidelines and limited to studies in English was performed (2014-2020) to identify relevant studies reporting effectiveness outcomes of belimumab in patients with SLE. A modified version of the Newcastle-Ottawa Scale was used to assess study quality. Outcomes, including SLE Disease Activity Index (SLEDAI) score, prednisone-equivalent use, and SLE flare were pooled and analyzed using statistical aggregation methods.ResultsThe literature search identified 514 articles for initial review. Of these, 17 articles were suitable for data extraction and summary. Baseline characteristics of patients in real-world studies were generally similar to those of relevant clinical trials, including age, sex, disease duration, SLEDAI score, and prednisone-equivalent use. Real-world use of belimumab was associated with reductions in SLEDAI score (mean baseline score to month 6: 10.1-4.4; 57% reduction), prednisone-equivalent dosing (mean baseline dose to month 6: 12.1 mg/day to 6.9 mg/day; 43% reduction), and flare frequency (12 months prior to belimumab to 12 months after belimumab: 1.15-0.39 mean flares per patient per year; 66% reduction). Long-term data (up to 2 years post-treatment initiation) for SLEDAI score and prednisone-equivalent dose indicated that improvements in both outcomes continue over time among patients remaining on therapy.ConclusionsIn the real-world setting, observed outcomes with belimumab for the treatment of SLE are consistent with those reported from randomized clinical trials. Improvements persist long-term for SLEDAI activity and prednisone-equivalent use with belimumab.

Dataset Information

Response to belimumab among patients with systemic lupus erythematosus in clinical practice settings: 24-month results from the OBSErve study in the USA.

Publications

Response to belimumab among patients with systemic lupus erythematosus in clinical practice settings: 24-month results from the OBSErve study in the USA.

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