Dataset Information

Real-World Effectiveness of Belimumab in the Treatment of Systemic Lupus Erythematosus: Pooled Analysis of Multi-Country Data from the OBSErve Studies.

ABSTRACT:

Introduction

The 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.

Methods

OBSErve (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.

Results

In 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).

Conclusions

Belimumab 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.

SUBMITTER: Collins CE

PROVIDER: S-EPMC7695800 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Publications

Real-World Effectiveness of Belimumab in the Treatment of Systemic Lupus Erythematosus: Pooled Analysis of Multi-Country Data from the OBSErve Studies.

Collins Christopher E CE Cortes-Hernández Josefina J Garcia Mercedes A MA von Kempis Johannes J Schwarting Andreas A Touma Zahi Z Kurtinecz Milena M Gairy Kerry K

Rheumatology and therapy 20201118 4

<h4>Introduction</h4>The 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.<h4>Methods</h4>OBSErve (Argentina, Canada, Germany, Spain, Switzerland, and the USA) enrolled adults ≥ 18 years of age with SLE, who were prescribed belimu ...[more]

PMID: 33206344

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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.

Project description:This study evaluated the real-world effectiveness of belimumab (BLM) in the treatment of systemic lupus erythematosus (SLE) patients with moderate to high disease activity. This retrospective cohort study enrolled 129 Japanese patients with moderate to high SLE disease activity who received BLM between January 2013 and March 2023. The clinical outcomes, including the flare-free survival, SLE Disease Activity Index 2000 (SLEDAI-2K) score, and prednisone-equivalent dose, in the BLM and mycophenolate mofetil (MMF) treatment groups were compared before and after treatment. Safety data for BLM were collected. Additionally, we compared the effectiveness of BLM and intravenous cyclophosphamide (IV-CY) treatment using the stabilized inverse probability of treatment weighting (IPTW) method based on the propensity scores. This observational study enrolled 129 patients with moderate/severe SLE: 48 patients received belimumab, 45 received IV-CY, and 36 received MMF and prednisolone for remission induction therapy. The median follow-up for the BLM group was 17.0 months. Among them, 19 received BLM plus MMF. BLM significantly reduced the mean SLEDAI-2K (from mean baseline to 52 weeks: 49.2% reduction from 12.8 to 6.5) and prednisone daily dose (from mean baseline to 52 weeks: 21.9% reduction from 12.8 to 10.0 mg/day). The flare-free survival at 52 weeks was not significantly different between the BLM and MMF groups. There was no significant difference in the flare-free survival rates or reduction rates of the SLEDAI-2K between the patients treated with BLM and those treated with BLM plus MMF. In the propensity score-matched comparative analyses, there was no significant difference in the flare-free survival rates or an estimated decline in the SLEDAI-2K scores between the patients with lupus treated with BLM and IV-CY. BLM may be a promising alternative treatment option for lupus patients with moderate or high disease activity who do not respond to conventional treatments.

Project description: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.

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.

Dataset Information

Real-World Effectiveness of Belimumab in the Treatment of Systemic Lupus Erythematosus: Pooled Analysis of Multi-Country Data from the OBSErve Studies.

Introduction

Methods

Results

Conclusions

Publications

Real-World Effectiveness of Belimumab in the Treatment of Systemic Lupus Erythematosus: Pooled Analysis of Multi-Country Data from the OBSErve Studies.

Similar Datasets

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