scholarly journals Organ damage in patients treated with belimumab versus standard of care: a propensity score-matched comparative analysis

2019 ◽  
Vol 78 (3) ◽  
pp. 372-379 ◽  
Author(s):  
Murray B Urowitz ◽  
Robert L Ohsfeldt ◽  
Ronald C Wielage ◽  
Kari A Kelton ◽  
Yumi Asukai ◽  
...  
Keyword(s):  
Propensity Score ◽  
Lupus Erythematosus ◽  
Damage Index ◽  
Standard Of Care ◽  
Organ Damage ◽  
Systemic Lupus ◽  
American College Of Rheumatology ◽  
Damage Progression

ObjectivesThe study (206347) compared organ damage progression in patients with systemic lupus erythematosus (SLE) who received belimumab in the BLISS long-term extension (LTE) study with propensity score (PS)-matched patients treated with standard of care (SoC) from the Toronto Lupus Cohort (TLC).MethodsA systematic literature review identified 17 known predictors of organ damage to calculate a PS for each patient. Patients from the BLISS LTE and the TLC were PS matched posthoc 1:1 based on their PS (±calliper). The primary endpoint was difference in change in Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) score from baseline to 5 years.ResultsFor the 5- year analysis, of 567 (BLISS LTE n=195; TLC n=372) patients, 99 from each cohort were 1:1 PS matched. Change in SDI score at Year 5 was significantly lower for patients treated with belimumab compared with SoC (−0.434; 95% CI –0.667 to –0.201; p<0.001). For the time to organ damage progression analysis (≥1 year follow-up), the sample included 965 (BLISS LTE n=259; TLC n=706) patients, of whom 179 from each cohort were PS-matched. Patients receiving belimumab were 61% less likely to progress to a higher SDI score over any given year compared with patients treated with SoC (HR 0.391; 95% CI 0.253 to 0.605; p<0.001). Among the SDI score increases, the proportion of increases ≥2 was greater in the SoC group compared with the belimumab group.ConclusionsPS-matched patients receiving belimumab had significantly less organ damage progression compared with patients receiving SoC.

scholarly journals Comparative analysis of long-term organ damage in patients with systemic lupus erythematosus using belimumab versus standard therapy: a post hoc longitudinal study

2020 ◽  
Vol 7 (1) ◽  
pp. e000412
Author(s):  
Murray B Urowitz ◽  
Robert L Ohsfeldt ◽  
Ronald C Wielage ◽  
John J Dever ◽  
Mehdi Zakerifar ◽  
...  
Keyword(s):  
Propensity Score ◽  
Propensity Score Matching ◽  
Standard Therapy ◽  
Organ Damage ◽  
Systemic Lupus ◽  
Damage Progression ◽  
Damage Accrual ◽  
Post Hoc

ObjectiveLong-term extension (LTE) studies of belimumab in SLE do not include a comparator arm, preventing comparisons between belimumab plus standard therapy and standard therapy alone for organ damage accrual. Propensity score matching can be used to match belimumab-treated patients from LTE studies with standard therapy–treated patients from observational cohort studies. This analysis was designed to compare organ damage progression between treatment groups (belimumab plus standard therapy vs standard therapy alone) in patients with SLE with ≥5 years of follow-up, reproducing our previous study with more generalisable data.MethodsThis exploratory post hoc analysis used a heterogeneous population of US and non-US patients receiving monthly intravenous belimumab from pooled BLISS LTE trials (BEL112234/NCT00712933) and standard therapy–treated patients from the Toronto Lupus Cohort. Sixteen clinical variables were selected to calculate the propensity score.ResultsThe 592 LTE and 381 Toronto Lupus Cohort patients were highly dissimilar across the 16 variables; an adequately balanced sample of 181 LTE and 181 matched Toronto Lupus Cohort patients (mean bias=3.7%) was created using propensity score matching. Belimumab treatment was associated with a smaller increase in Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) over 5 years than standard therapy alone (mean treatment difference=–0.453 (95% CI –0.646 to –0.260); p<0.001). Patients treated with belimumab were 60% less likely to progress to a higher SDI score over any given year of follow-up, compared with standard therapy alone (HR (95% CI) 0.397 (0.275 to 0.572); p<0.001).ConclusionUsing propensity score matching, this highly heterogeneous sample was sufficiently matched to the Toronto Lupus Cohort, suggesting that patients treated with intravenous belimumab may have reduced organ damage progression versus standard therapy alone. This analysis of a large and diverse pooled SLE population was consistent with our previously published US-focused study.

Childhood Systemic Lupus Erythematosus: Presentation, management and long-term outcomes in an Australian cohort

Lupus ◽  
2022 ◽  
pp. 096120332110697
Author(s):  
Megan P Cann ◽  
Anne M Sage ◽  
Elizabeth McKinnon ◽  
Senq-J Lee ◽  
Deborah Tunbridge ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Incidence Rate ◽  
Lupus Erythematosus ◽  
Renal Involvement ◽  
Damage Index ◽  
Organ Damage ◽  
Systemic Lupus ◽  
End Organ Damage ◽  
American College Of Rheumatology

Objectives Systemic Lupus Erythematosus (SLE) is a serious autoimmune disease often resulting in major end-organ damage and increased mortality. Currently, no data exists focussing on the presentation, long-term management and progression of SLE in the Australian paediatric population. We conducted the first Australian longitudinal review of childhood SLE, focussing on response to treatment and outcomes. Methods Detailed clinical and laboratory data of 42 children diagnosed with SLE before 16 years from 1998 to 2018 resident in Western Australia was collected. Data was collected at diagnosis and key clinical review time points and compared using the Systemic Lupus Collaborating Clinics (SLICC) and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) criteria. End organ damage was assessed against Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). Incidence rates of disease complications and end organ damage were determined. Results Of the 42 children, 88% were female with average age at diagnosis of 12.5 years. Indigenous Australians were over represented with an incidence rate 18-fold higher than non-Indigenous, although most children were Caucasian, reflecting the demographics of the Australian population. Median duration of follow-up was 4.25 years. On final review, 28.6% had developed cumulative organ damage as described by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (incidence rate: 0.08/PY (95% CI 0.04–0.14)), and one child died. Twenty-nine children had renal involvement (incidence rate: 0.38/PY (95% CI 0.26–0.56)). Of the 27 patients with biopsy proven lupus nephritis, 70% had Class III or IV disease. Average length of prednisolone use from diagnosis was 32.5 months. Hydroxychloroquine ( n = 36) and mycophenolate mofetil ( n =21) were the most widely used steroid sparing agents. 61.9% received rituximab and/or cyclophosphamide. Conclusion This is the first longitudinal retrospective review of Australian children with SLE, with a markedly higher incidence in Indigenous children. Although improving, rates of end organ complications remain high, similar to international cohort outcomes. Longitudinal multi-centre research is crucial to elucidate risk factors for poor outcomes, and identifying those warranting early more aggressive therapy.

scholarly journals Long-term safety and limited organ damage in patients with systemic lupus erythematosus treated with belimumab: a Phase III study extension

Rheumatology ◽  
2019 ◽  
Vol 59 (2) ◽  
pp. 281-291 ◽  
Author(s):  
Ronald F van Vollenhoven ◽  
Sandra V Navarra ◽  
Roger A Levy ◽  
Mathew Thomas ◽  
Amy Heath ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Damage Index ◽  
Organ Damage ◽  
Index Score ◽  
Phase Iii ◽  
Extension Study ◽  
Laboratory Parameters ◽  
Damage Accrual

AbstractObjectiveThis extension study of the Phase III, randomized, placebo-controlled Belimumab International SLE Study (BLISS)-52 and BLISS-76 studies allowed non-US patients with SLE to continue belimumab treatment, in order to evaluate its long-term safety and tolerability including organ damage accrual.MethodsIn this multicentre, long-term extension study (GlaxoSmithKline Study BEL112234) patients received i.v. belimumab every 4 weeks plus standard therapy. Adverse events (AEs) were assessed monthly and safety-associated laboratory parameters were assessed at regular intervals. Organ damage (SLICC/ACR Damage Index) was assessed every 48 weeks. The study continued until belimumab was commercially available, with a subsequent 8-week follow-up period.ResultsA total of 738 patients entered the extension study and 735/738 (99.6%) received one or more doses of belimumab. Annual incidence of AEs, including serious and severe AEs, remained stable or declined over time. Sixty-nine (9.4%) patients experienced an AE resulting in discontinuation of belimumab or withdrawal from the study. Eleven deaths occurred (and two during post-treatment follow-up), including one (cardiogenic shock) considered possibly related to belimumab. Laboratory parameters generally remained stable. The mean (s.d.) SLICC/ACR Damage Index score was 0.6 (1.02) at baseline (prior to the first dose of belimumab) and remained stable. At study year 8, 57/65 (87.7%) patients had no change in SLICC/ACR Damage Index score from baseline, indicating low organ damage accrual.ConclusionBelimumab displayed a stable safety profile with no new safety signals. There was minimal organ damage progression over 8 years.Trial registrationClinicalTrials.gov, https://clinicaltrials.gov, NCT00424476 (BLISS-52), NCT00410384 (BLISS-76), NCT00732940 (BEL112232), NCT00712933 (BEL112234).

scholarly journals Clinical profile of systemic lupus erythematosus among children less than 12 years

2018 ◽  
Vol 5 (2) ◽  
pp. 343
Author(s):  
Senthil Kumar Andy ◽  
Elayaraja Kandasamy
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Damage Index ◽  
Organ Damage ◽  
Clinical Profile ◽  
Connective Tissues ◽  
Systemic Lupus ◽  
Initial Manifestation ◽  
Double Stranded Dna

Background: Systemic lupus erythematosus (SLE) is an episodic multisystem autoimmune disease characterized by widespread inflammation of blood vessels and connective tissues and by the presence of antinuclear antibodies especially antibodies to native double stranded DNA. The aim was to study the clinical profile of SLE among children less than 12 years attending an urban referral hospital, SLEDAI scoring at onset and follow up at 1 year and SLICC/ACR damage index at 1 year.Methods: A descriptive, prospective and observational study was conducted in Medical, Nephrology, Rheumatology OPD wards, in ICH and HC, from November 2007 to August 2009 among all children diagnosed to have SLE. Results: In this study there were 50 cases over the last 2 years. Majority of the children were diagnosed within a year of their initial manifestation. The mean age at the time of onset of symptoms was 7.94 years. Female to male ratio in our study is 2.5:1.Conclusions: Efforts should be directed in diagnosing at earlier stage itself for better outcome. SLEDAI and SLICC/ACR DI can be incorporated in routine follow up to detect mild to moderate and severe flare and extent of organ damage.

SAT0179 ADHERENCE TO HYDROXYCHLOROQUINE INFLUENCES THE INCIDENCE OF ORGAN DAMAGE DURING FOLLOW-UP IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1031.1-1031
Author(s):  
J. H. Kang ◽  
S. E. Choi ◽  
H. Xu ◽  
D. J. Park ◽  
S. S. Lee
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Damage Index ◽  
Clinical Manifestations ◽  
Medication Possession Ratio ◽  
Organ Damage ◽  
Systemic Lupus ◽  
Laboratory Findings ◽  
The Impact

Background:Objectives:Hydroxychloroquine (HCQ) is a cornerstone drug in patients with systemic lupus erythematosus (SLE), decreasing the risk of flares and comorbidities and improving survival. This study investigated the effects of HCQ adherence on clinical manifestations, disease activity, and organ damage in Korean patients with SLE.Methods:Data on 299 SLE patients were obtained from the Korean Lupus Network registry. Demographic variables, clinical manifestations, laboratory findings, PGA, and SLEDAI-2000 and SLICC damage index scores were recorded at the time of enrollment and repeated annually for 4 consecutive years. Patients were divided into two groups according to the level of HCQ adherence. Adherence was defined by the medication possession ratio and dichotomized as ≤ 80% vs. > 80%. Univariate and multivariate analyses were performed to assess the impact of adherence to HCQ on clinical outcomes.Results:Of the 299 patients, 31 (10.4%) showed poor drug adherence during the follow-up period. Patients with poor HCQ adherence were older (P=0.011), less insured (P=0.024), experienced lower employment (P=0.033), and had a higher rate of comorbidities such as hypertension (P=0.048) and depression (P<0.001). The non-adherent group had higher mean and changed SLICC damage index scores than the adherent group across all 4 years. In the multivariate analysis, HCQ non-adherence was significantly associated with older age (OR, 1.043; 95% CI, 1.006–1.081; P=0.021), depression (OR, 11.98; 95% CI, 1.099–130.6; P=0.042), and an annual increase in the SLICC damage index score (OR, 2.275; 95% CI, 1.369–3.779; P=0.002).Conclusion:HCQ adherence might be influenced by age and depressive mood. Additionally, the poor adherence to HCQ in SLE patients was correlated with higher cumulative organ damage. Therefore, patients with SLE should be educated to take HCQ appropriately to improve their clinical outcome in clinical practice.Disclosure of Interests:None declared

Lupus nephritis is associated with more corticosteroid-associated organ damage but less corticosteroid non-associated organ damage

Lupus ◽  
2016 ◽  
Vol 26 (6) ◽  
pp. 598-605 ◽  
Author(s):  
Y B Joo ◽  
S Won ◽  
C-B Choi ◽  
S-C Bae
Keyword(s):  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Immunosuppressive Agents ◽  
Damage Index ◽  
Organ Damage ◽  
Standardized Mortality Ratio ◽  
Systemic Lupus ◽  
American College Of Rheumatology ◽  
Mortality Ratio ◽  
Standardized Mortality Ratios

Objective The objective of this study was to investigate the association of lupus nephritis on organ damage and mortality in patients with systemic lupus erythematosus (SLE). Methods A total of 1112 patients with SLE were investigated. Lupus nephritis was defined as a proteinuria based on the 1997 American College of Rheumatology criteria. Damage was assessed using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index. The associations of lupus nephritis with overall, non-renal, corticosteroid-associated, and non-associated damage were analyzed using logistic regression. The age-adjusted and sex-adjusted standardized mortality ratio was evaluated in patients with and without lupus nephritis. Results The prevalence of lupus nephritis in patients with SLE was 46.3%. Patients with lupus nephritis had a higher percentage of overall cumulative damage than patients without lupus nephritis (51.5% vs. 35.7%, p < 0.001). The odds ratio was 1.40 after adjusting for age at SLE diagnosis, sex, disease duration, anti-malarial agents, immunosuppressive agents and cumulative corticosteroid dose. Among non-renal damage, the odds of corticosteroid-associated damage were higher (2.06, 95% confidence interval (CI) 1.43–2.96) whereas the odds of non-associated damage were lower (0.50, 95% CI 0.35–0.75) in patients with lupus nephritis. The standardized mortality ratios of patients with and without lupus nephritis were 5.17 (95% CI 3.49–7.38) and 2.32 (95% CI 1.47–3.48), respectively. Conclusion In patients with SLE, the presence of lupus nephritis is associated with increased corticosteroid-associated damage but less corticosteroid non-associated damage. Also, mortality is significantly higher in patients with lupus nephritis than in those without lupus nephritis.

scholarly journals FRI0146 SLICC/ACR DAMAGE INDEX IN PATIENTS WITH ANTIPHOSPHOLIPID SYNDROME WITH AND WITHOUT SYSTEMIC LUPUS ERYTHEMATOSUS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 657.2-657
Author(s):  
F. Cheldieva ◽  
T. Reshetnyak ◽  
A. Shumilova ◽  
N. Kosheleva ◽  
T. Lisitsyna ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Independent Predictor ◽  
Damage Index ◽  
Organ Damage ◽  
Systemic Lupus ◽  
Group Iii ◽  
Group I ◽  
Group Ii

Background:The role of antiphospholipid syndrome (APS) as a cause of chronic organ damage in patients with systemic lupus erythematosus (SLE) is important. While acute disease manifestations of APS are well known, information on the long-term prognosis and damage in affected patients is still very limited.Objectives:Тo assess the severity of organ damage in patients with APS without SLE and with concomitant SLE, as well as the feature of irreversible damage to internal organs in patients with primary APS during a dynamic observation using SLICC/ACR Damage Index (SDI).Methods:Тhe study included 195 patients (41 men and 154 women) who were observed at the Institute of Rheumatology from 2007 to June 2018 with a diagnosis of SLE and APS. The study inclusion criteria were: a follow-up period of at least 3 years with the study of serological markers of APS for previous years, the possibility of dynamic monitoring of patients, patient consent. Patients were divided into 3 groups, depending on presence of APS: group I -SLE with APS (n=99 with average age 34.6 [25-44), group II - SLE without APS (n=45; 33.5[26-42]) and group III - 45 (average age 37.7 [27-46]) patients with primary APS (PAPS) diagnosed according to international diagnostic criteria, without signs of any disease. In all three groups organ damage was assessed using SDI. SDI 1-2 points corresponded to moderate damage, more than 2 points - to severe.Results:A linear increase in irreversible organ damage was noted over 10 years of follow-up. At the time of inclusion in the study, the average SDI was significantly higher in the SLE + APS group than in the SLE group: 1.32 versus 0 when included (p <0.0001). A direct correlation was found between the age of patients and the value of SDI both in the group I (p=0.004, r=0.284) and in the group II (p=0.04, r=0.281) when included in the study. There was a direct correlation between the activity of the disease on the SLEDAI at the end of the study and the value of SDI (p=0.03, r=0.41) in the group II. The number of patients by the 10th year of follow-up remained in group I were 44 of 99, in group II - 24 of 51 and in group III - 14 of 45. SDI was more than 2 points in 39 (89%) of 44 patients in group I, in 12 (50%) of 24 in group II and 9 (65%) of 14 in Group III (p=0.0002 OR=13; 95% CI 2,4-70). 5 years after the start of the observation average SDI in group I and II was 2.5 and 1.3 (p <0.0001) and after 10 years - 2.8 and 1.9 (p = 0.0008) accordingly. An increase of total SDI occurred primarily due to damage to peripheral vessels due to the large number of thromboses (in 55% of patients) in the group II. Using step-by-step multiple logistic regressions in the study groups only APS was an independent predictor of increased SDI. The most common cause of an increase in SDI in the PAPS group was damage to peripheral vessels (64%) as a result of a high frequency of venous thrombosis, followed by damage to the neuropsychiatric system (55%) and the cardiovascular system (40%).Conclusion:APS is an independent predictor of increased SDI. The determination of irreversible organ damage in patients with PAPS using SDI allows us to assess the functional disorders of organs and systems and can be used in clinical practice in these patients.Disclosure of Interests:None declared

scholarly journals Impact of glucocorticoids on the incidence of lupus-related major organ damage: a systematic literature review and meta-regression analysis of longitudinal observational studies

2021 ◽  
Vol 8 (1) ◽  
pp. e000590
Author(s):  
Manuel Francisco Ugarte-Gil ◽  
Anselm Mak ◽  
Joanna Leong ◽  
Bhushan Dharmadhikari ◽  
Nien Yee Kow ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Observational Studies ◽  
Case Reports ◽  
Damage Index ◽  
Organ Damage ◽  
Systemic Lupus ◽  
Major Organ ◽  
Meta Regression ◽  
Longitudinal Observational Studies

ObjectiveIn systemic lupus erythematosus (SLE), disease activity and glucocorticoid (GC) exposure are known to contribute to irreversible organ damage. We aimed to examine the association between GC exposure and organ damage occurrence.MethodsWe conducted a literature search (PubMed (Medline), Embase and Cochrane January 1966–October 2021). We identified original longitudinal observational studies reporting GC exposure as the proportion of users and/or GC use with dose information as well as the occurrence of new major organ damage as defined in the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index. Meta-regression analyses were performed. Reviews, case-reports and studies with <5 years of follow-up, <50 patients, different outcomes and special populations were excluded.ResultsWe selected 49 articles including 16 224 patients, 14 755 (90.9%) female with a mean age and disease duration of 35.1 years and of 37.1 months. The mean follow-up time was 104.9 months. For individual damage items, the average daily GC dose was associated with the occurrence of overall cardiovascular events and with osteoporosis with fractures. A higher average cumulative dose adjusted (or not)/number of follow-up years and a higher proportion of patients on GC were associated with the occurrence of osteonecrosis.ConclusionsWe confirm associations of GC use with three specific damage items. In treating patients with SLE, our aim should be to maximise the efficacy of GC and to minimise their harms.

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