OP0252 Organ damage progression and long-term safety of belimumab (BEL) in patients with systemic lupus erythematosus (SLE): an extension of pivotal phase 3 bliss studies

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.

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PMS3 Calibration of a Cost-Effectiveness MODEL for Systemic LUPUS Erythematosus Using NEWLY Observed LONG-TERM Organ Damage DATA

Value in Health Regional Issues ◽

10.1016/j.vhri.2020.07.342 ◽

2020 ◽

Vol 22 ◽

pp. S65

Author(s):

Y. Asukai ◽

C. Gait ◽

M. Treur

Keyword(s):

Systemic Lupus Erythematosus ◽

Cost Effectiveness ◽

Lupus Erythematosus ◽

Organ Damage ◽

Systemic Lupus ◽

Effectiveness Model ◽

Damage Data

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SAT0193 A PHASE 3, OPEN-LABEL, CONTINUATION STUDY EVALUATING LONG-TERM SAFETY AND EFFICACY OF BELIMUMAB IN PATIENTS FROM JAPAN AND KOREA WITH SYSTEMIC LUPUS ERYTHEMATOSUS, FOR UP TO 7 YEARS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.5783 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1038.2-1039

Author(s):

Y. Tanaka ◽

S. C. Bae ◽

D. Bass ◽

M. Chu ◽

P. Curtis ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Systemic Lupus ◽

Open Label ◽

Phase 3 ◽

Safety And Efficacy ◽

Sledai Score ◽

Organ Domain ◽

Domain Scores

Background:Systemic lupus erythematosus (SLE) is an autoimmune disorder more prevalent in the Asian population vs Caucasians. Belimumab (BEL), a monoclonal antibody targeting B-lymphocyte stimulator, is approved in patients (pts) ≥5 years with active, autoantibody-positive SLE.Objectives:Evaluate long-term safety and efficacy of intravenous (IV) BEL + standard SLE therapy (SST) in pts with SLE in Japan/Korea.Methods:In this Phase 3, multicentre, open-label (OL) study (BEL114333;NCT01597622), eligible (≥18 years of age) completers of the double-blind phase of GSK study BEL113750 in Japan and South Korea or the subcutaneous OL phase of GSK Study BEL112341 in Japan, received monthly BEL 10 mg/kg IV plus SST. Primary endpoints: safety assessments. Key secondary endpoints: SRI4 response rate at each scheduled visit (observed data), defined as a ≥4-point reduction from baseline in SELENA-SLEDAI score, no worsening in PGA (<0.3-point increase from baseline) and no new BILAG 1A/2B organ domain scores; time to first severe SFI flare over time. Endpoints were analysed relative to first BEL dose (parent or current study). No follow-up data were collected after study withdrawal.Results:Overall, 142 pts were enrolled (Japan n=72; Korea n=70), 104 (73.2%) completed the study, 1 (0.7%) died and 37 (26.1%) withdrew.Overall, 139 (97.9%) pts had ≥1 adverse event (AE) (Table). Most frequent AEs included: nasopharyngitis (60.6%); headache (28.2%); cough, herpes zoster and viral upper respiratory tract infection (18.3% each). Serious AEs (SAEs) occurred in 48 (33.8%) pts. Most common SAEs were infections and infestations, reported in 24 (16.9%) pts (Table). During this study, the annual incidence of AEs, including SAEs and AESI, remained stable or declined, with no trends of clinical concerns regarding the incidence of Grade 3 or 4 values for laboratory parameters. There was 1 transient positive immunogenicity result of no clinical concern.Table.The proportion of SRI4 responders was 47.8% at Year 1 (Week 24) and tended to increase numerically up to 84.6% at Year 7 (Week 48). The proportion of pts with a ≥4-point decrease from baseline in SELENA-SLEDAI score numerically increased from 51.5% at Year 1 (Week 24) to 84.6% at Year 7 (Week 48). Proportion of pts with no PGA worsening was 91.3-100% and the proportion with no new BILAG 1A/2B organ domain scores was 93.3-100% up to Year 7 (Week 48). A total of 21 (14.8%) pts had 24 severe SFI flares.Conclusion:BEL was well tolerated as add-on therapy to SST for ≤7 years in pts with SLE from Japan/Korea. Safety results were consistent with the known BEL safety profile.Study funding: GSK.Disclosure of Interests:Yoshiya Tanaka Grant/research support from: Received research grants from Asahi-Kasei, Mitsubishi-Tanabe, Chugai, Takeda, Sanofi, Bristol-Myers, UCB, Daiichi-Sankyo, Eisai, Ono, Speakers bureau: Received speaking fees and/or honoraria from Daiichi-Sankyo, Astellas, Chugai, Eli Lilly, Pfizer, AbbVie, YL Biologics, Bristol-Myers, Takeda, Mitsubishi-Tanabe, Novartis, Eisai, Janssen, Teijin, Sang-Cheol Bae: None declared, Damon Bass Shareholder of: GSK, Employee of: GSK, Myron Chu Shareholder of: GSK, Employee of: GSK, Paula Curtis Shareholder of: GSK, Employee of: GSK, Kathleen DeRose Shareholder of: GSK, Employee of: GSK, Beulah Ji Shareholder of: GSK, Employee of: GSK, Regina Kurrasch Shareholder of: GSK, Employee of: GSK, Jenny Lowe Shareholder of: GSK, Employee of: GSK, Paige Meizlik Shareholder of: GSK, Employee of: GSK, David Roth Shareholder of: GSK, Employee of: GSK

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Resolution of the Expert Council «The role of type I interferon inhibitor in the treatment of patients with systemic lupus erythematosus»

Modern Rheumatology Journal ◽

10.14412/1996-7012-2021-4-126-128 ◽

2021 ◽

Vol 15 (4) ◽

pp. 126-128

Author(s):

A. M. Lila ◽

S. K. Soloviev ◽

T. V. Popkova

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Organ Damage ◽

Immunosuppressive Drugs ◽

Type I ◽

Type I Ifn ◽

Systemic Lupus ◽

Key Points

On April 28, 2021, a meeting of the Council of Experts was held with the participation of the leading experts in the field of rheumatic diseases, approaches to the treatment of patients with systemic lupus erythematosus (SLE) were discussed. The issues of medical care for patients with SLE and their routing, key points of Russian and international clinical guidelines for the management of patients with SLE, as well as the role of interferon (IFN) type I in the pathogenesis of the disease were discussed. It is noted that the management of patients with SLE requires a multidisciplinary approach. The basis of therapy is the use of glucocorticoids (GC), immunosuppressive drugs and their combinations. But long-term use of GC in patients with SLE leads to severe complications. Early prescription of biological disease-modifying antirheumatic drugs (bDMARDs) allows to achieve the greatest effect and prevent the development of irreversible organ damage associated with SLE. Currently data from three clinical trials on the efficacy and safety of the type I IFN inhibitor anifrolumab are available. During the discussion, experts defined the clinical profile of a patient with SLE, for whom administration of bDMARD therapy is indicated. According to experts, the use of a type I IFN inhibitor in routine clinical practice can improve disease outcomes in both short and long term.

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Treatment of Systemic Lupus Erythematosus

Korean Journal of Medicine ◽

10.3904/kjm.2020.95.3.162 ◽

2020 ◽

Vol 95 (3) ◽

pp. 162-169

Author(s):

Bo Young Kim ◽

Sung-Soo Kim

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Immunosuppressive Agents ◽

Organ Damage ◽

Long Term Outcomes ◽

Systemic Lupus ◽

Multiple Organs ◽

Organ Manifestations ◽

Specific Organ

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of autoantibodies that result in the inflammation of multiple organs, including the skin and musculoskeletal, renal, nervous, cardiovascular, respiratory, and gastrointestinal systems. Treatment includes the use of immunomodulatory and immunosuppressive agents to target specific organ manifestations. The treatment goal in SLE is to reduce disease activity and prevent organ damage and death. Optimal long-term outcomes require not only treatment of the disease, but also the management of comorbidities. This paper reviews treatments of SLE with the aim of improving outcomes.

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Problems of low activity and remission in systemic lupus erythematosus

Rheumatology Science and Practice ◽

10.14412/1995-4484-2019-218-221 ◽

2019 ◽

Vol 57 (2) ◽

pp. 218-221 ◽

Cited By ~ 3

Author(s):

S. K. Soloviev ◽

E. A. Aseeva ◽

E. G. Zotkin ◽

S. Yu. Kireeva ◽

E. L. Nasonov

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Organ Damage ◽

Systemic Lupus ◽

Term Survival ◽

Long Term Survival ◽

Definition Of ◽

Low Activity

In recent years, the long-term survival of patients with systemic lupus erythematosus (SLE) has increased to more than 90%, but there are still quite a few unresolved problems. Although the main objective of the concept of «Treatment of SLE to target» is «remission of symptoms and absence of organ damage», it was recognized that there is currently no generally accepted definition of remission in SLE. The article discusses different variants of the definition of «remission» in SLE.

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

Lupus ◽

10.1177/09612033211069765 ◽

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.

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POS0739 DEVELOPMENT OF A CONCEPTUAL MODEL TO UNDERSTAND DISEASE BURDEN IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS AND LONG-TERM ORGAN DAMAGE

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.1907 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 621.1-621

Author(s):

L. Broderick ◽

W. H. Chen ◽

R. Levy ◽

A. Foster ◽

C. Umanzor ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Literature Review ◽

Conceptual Model ◽

Patient Experience ◽

Lupus Erythematosus ◽

Disease Burden ◽

Organ Damage ◽

Systemic Lupus ◽

Patient Burden

Background:Systemic lupus erythematosus (SLE) is a chronic, multisystem, autoimmune disease resulting in increased morbidity and mortality and reduced health-related quality of life (HRQoL). Patients with SLE are at risk of developing irreversible long-term organ damage (LTOD) caused by both disease activity and cumulative medication toxicities. Data regarding the overall disease burden and impact of LTOD in patients with SLE are limited.Objectives:The primary objective of this qualitative study was to develop a conceptual model to describe the burden experienced by patients with SLE and LTOD.Methods:This study (GSK Study 209754) was conducted in three phases. First, a targeted literature review was performed to aid the development of an initial draft conceptual model. Key opinion leaders (KOLs) with experience in SLE and LTOD were then interviewed to assess the clarity, language, comprehensibility, and potential use of the conceptual model, and to help shape the patient interview materials. Finally, one-on-one interviews were performed with patients with SLE and LTOD in any of the 12 organ areas (defined by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index [SDI]), to gather patient perspectives on the common symptoms, functional impacts, treatment experiences, and HRQoL factors associated with LTOD. Data from the interviews were coded and analysed using NVivo software to identify patterns in responses concerning the key concepts of the overall patient burden of LTOD, and used to identify concepts to include in the model.Results:The literature review produced the preliminary conceptual model of LTOD. Results of the KOL interviews (n=5 clinicians and n=1 patient advocate) indicated that the preliminary conceptual model broadly captured the patient experience of LTOD. KOLs emphasised the difference between SLE activity (flares) and LTOD; the conceptual model was subsequently updated in accordance with these recommendations. Interviews conducted with patients with confirmed single (n=9) and multiple LTOD (n=31) indicated that the burden of LTOD associated with SLE was more severe, debilitating, and life threatening than that caused by SLE flares. Almost all patients (39/40) reported aspects of their lives that were more severely affected since their LTOD diagnosis. All 40 patients reported LTOD-related physical impacts, which often affected patients’ ability to perform everyday tasks. The most frequent physical impacts reported were a loss of vitality (39/40), long-term complications (e.g. unstable blood pressure, extreme pain, poor mobility, inflammation, dialysis, infection; 36/40), and severe fatigue (29/40). Cognitive impairments that became more pronounced after their LTOD diagnosis were reported by 27/40 of patients. Typically characterised as “brain fog”, these impairments were described as slower cognitive processing, forgetfulness, confusion, and aphasia. Economic impacts associated with LTOD included patients’ inability to work (31/40), costs of care (33/40), and non-medical-related costs (17/30). Psychosocial impacts reported by patients with LTOD affected their emotional state (39/40), ability to socialise (40/40) and relationships (30/40). Additionally, 30/40 patients reported symptoms as more severe since their LTOD diagnosis, including pain (14/40), fatigue (9/40), and oedema (8/40). Patients’ treatment goals were largely aligned with their experienced impacts of LTOD, including managing the disease and symptoms (25/40), limiting further organ damage (15/40), and improving HRQoL (11/40).Conclusion:The findings from this research clearly indicate that the patient burden of LTOD far surpasses that of SLE without LTOD. These data were incorporated and refined into a conceptual model that fully represents the patient experience of LTOD. The model will help researchers, clinicians, and patients to better understand the impact of SLE-related LTOD progression.Funding:GSKAcknowledgements:Medical writing assistance was provided by Casmira Brazaitis, PhD, Fishawack Indicia Ltd., UK, part of Fishawack Health, and was funded by GSK.Disclosure of Interests:Lynne Broderick Consultant of: GSK, Wen-Hung Chen Shareholder of: GSK, Employee of: GSK, Roger Levy Shareholder of: GSK, Employee of: GSK, April Foster Consultant of: GSK, Cindy Umanzor Consultant of: GSK, Deven Chauhan Shareholder of: GSK, Employee of: GSK

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Long-term outcomes of patients with systemic lupus erythematosus: A Multicenter Cohort Study from CSTAR registry

Rheumatology and Immunology Research ◽

10.2478/rir-2021-0025 ◽

2021 ◽

Vol 2 (3) ◽

pp. 195-202

Author(s):

Ziqian Wang ◽

Mengtao Li ◽

Zhizhong Ye ◽

Caifeng Li ◽

Zhijun Li ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Logistic Regression ◽

Regression Analysis ◽

Survival Rate ◽

Lupus Erythematosus ◽

Disease Onset ◽

Organ Damage ◽

Long Term Outcomes ◽

Systemic Lupus

Abstract Objective To study the long-term outcomes, in the context of both mortality and organ damage in patients with systemic lupus erythematosus (SLE) in the Chinese SLE Treatment and Research group (CSTAR) registry cohort. Methods Patients were enrolled from April 2009 to February 2010 and they were followed up. The demographic data, clinical manifestations, labs test results and imaging examinations, disease activity (SLEDAI-2K), damage scores (SLLIC/Damage Index [SDI]), and medications were collected. Data were censored at either the last clinic visit or telephonic interview. Survival rate was analyzed by Kaplan–Meier (KM) method. COX proportional hazard model was adopted to perform the analysis of predicting factors for mortality and organ damage. Logistic regression analysis was employed to discuss the relationship among mortality, organ damage, and flare. Results A total of 2104 patients were recruited at baseline and 1494 patients were followed up. The cumulative 1-year, 3-year, and 5-year survival rates were 98.3%, 96.9%, and 95.7%, respectively. Seventy-eight patients died during follow-up, and the main causes of death were infection (34.6%), active disease (26.9%), cardiovascular and cerebrovascular events (5.13%), and malignancy (5.13%). At entry, 247 patients presented with irreversible organ damage and it increased to 398 patients at the endpoint. The major accumulated organ damages were kidney (25.9%), musculoskeletal disease (20.2%), neuropsychiatric disease (12.2%), and pulmonary damage (10.9%). Cox regression analysis further showed that male, late disease onset, delayed diagnosis (diagnosis from disease onset >1 year), baseline organ damage, and specific organ involvements predicted for higher mortality. In addition, early disease onset was a protecting factor for organ damage, and anti-SSA was an independent predicting factor for new organ damage. Logistic regression analysis showed that flare predicted for more organ damage. Conclusion The 5-year survival rate of Chinese SLE patients has improved and is comparable to Caucasians SLE patients. Disease flare impact on prognosis is the increasing risk of damage development. Early diagnosis, prevention for flare and damage to maintain remission, may improve outcome.

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