scholarly journals Determinants and protective associations of the lupus low disease activity state in a prospective Chinese cohort

2021 ◽  
Author(s):  
Yanjie Hao ◽  
Shereen Oon ◽  
Lanlan Ji ◽  
Dai Gao ◽  
Yong Fan ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Serum Creatinine ◽  
Disease Activity ◽  
Protective Factor ◽  
Treat To Target ◽  
Low Disease Activity ◽  
Damage Accrual ◽  
Chinese Cohort ◽  
Activity State

Abstract Objective To investigate the frequency and determinants of achieving the lupus low disease activity state (LLDAS), and the effect of LLDAS attainment on disease flare and damage accrual in a prospective, single-center cohort of Chinese lupus patients. Methods Baseline and follow-up data from consecutive patients at the Peking University First Hospital were collected from January 2017 to June 2020. Results A total of 185 patients were enrolled, with median (range) disease duration at enrolment of 2.3 (0.8–7.7) years, and median follow-up of 2.2 (1.0–2.9) years. By the end of the study, 139 (75.1%) patients had achieved LLDAS at least once; 82 (44.3%) patients achieved LLDAS for ≥ 50% of observations. Multivariable logistic regression analysis showed that 24-h urinary total protein (UTP; per g) (OR = 0.447, 95%CI [0.207–0.968], p = 0.041), serum creatinine (Scr; per 10 µmol/L) (OR = 0.72, 95%CI [0.52–0.99], p = 0.040), and C3 level (per 100 mg/L) (OR = 1.60, 95%CI [1.18–2.17], p = 0.003) at recruitment had independent negative associations with achieving LLDAS for ≥ 50% of observations. Kaplan–Meier analyses showed a significant reduction in flare rate with increased proportion of time in LLDAS. Attainment of LLDAS in at least 50% of observations was an independent protective factor for damage accrual (OR = 0.19, 95%CI [0.04–0.99], p = 0.049). Conclusions In this prospective Chinese cohort, LLDAS was an attainable goal in clinical practice. Nephritis-related markers (UTP and Scr) and C3 level at recruitment negatively influenced achievement of LLDAS. LLDAS achievement was significantly protective from flare and damage accrual. Key points • Low disease activity status (LLDAS) is an achievable target during SLE treatment in China. Urine protein, serum creatinine, and C3 level at recruitment independently affect LLDAS achievement in this group of Chinese lupus patients. • As a treatment target, LLDAS achievement has a highly protective effect for preventing flare and damage accrual, especially in case of achieving LLDAS for ≥ 50% of observations. • The present results further highlight the practical significance of treat-to-target principle in SLE management (T2T/SLE) and the needs for promoting the application of T2T/SLE in clinical practice as well as exploring the concrete implement strategy.

scholarly journals AB0376 DETERMINANTS AND PROTECTIVE EFFECTS OF A LOW DISEASE ACTIVITY STATE IN SYSTEMIC LUPUS ERYTHEMATOSUS: RESULTS FROM A PROSPECTIVE CHINESE COHORT

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1488-1489
Author(s):  
Y. Hao ◽  
L. Ji ◽  
D. Gao ◽  
Y. Fan ◽  
E. F. Morand ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Asia Pacific ◽  
Systemic Lupus ◽  
Low Disease Activity ◽  
Disease Flare ◽  
Damage Accrual ◽  
Activity State

Background:The concept of treat to target in systemic lupus erythematosus has moved forward in recent years. The Lupus low disease activity state (LLDAS) defined by the Asia-Pacific Lupus Collaboration (APLC) in 2016 has been validated prospectively in the APLC cohort itself and retrospectively in multiple other cohorts.Objectives:The concept of treat to target in systemic lupus erythematosus has moved forward in recent years. The Lupus low disease activity state (LLDAS) defined by the Asia-Pacific Lupus Collaboration (APLC) in 2016 has been validated prospectively in the APLC cohort itself and retrospectively in multiple other cohorts. The aim of this study was to investigate the frequency and determinants of achieving LLDAS, and the influence of LLDAS on short term outcomes including disease flare and damage accrual in Chinese lupus patients.Methods:The baseline and follow-up data of all consecutive patients in a longitudinal lupus cohort from January 2017 to December 2018 were collected prospectively. SLEDAI-2K, PGA and disease flare were assessed at each follow-up visit, and further compared to the previous routine clinical visits. Irreversible disease damage was captured using the SLICC damage index and the short form (36) health survey for health-related quality of life was completed annually.Results:One hundred and forty-nine patients were enrolled, with the median disease duration at recruitment of 2.4 (0.9–8.2) years, and median follow-up of 15.4 (10.1-18.2) months. By the end of the study, 104 (69.8%) patients achieved LLDAS at least once; 59 patients achieved LLDAS for≥50% of observations. Multivariate logistic regression analysis showed that age at disease onset< 30 years (OR=0.05, 95%CI [0.01-0.59], p=0.017), 24-hour urine total protein (UTP) level at recruitment (OR=0.9992, 95%CI [0.9987-0.9998], p=0.007), and C3 level (OR=1.004, 95%CI [1.001-1.008], p=0.024) had independent associations with achieving LLDAS for≥50% of all observations (Table 1). During follow-up, 56 (37.6%) patients experienced disease flare including 14 (9.4%) patients with severe flare. Kaplan-Meier analyses showed significant differences in flare rates according to whether LLDAS was achieved and the percentage follow-up time in LLDAS (Figure 1). Multivariate cox analysis revealed that the percentage time of time in LLDAS was an independent negative determinant of disease flare (HR=0.18, 95% CI [0.07-0.48], p=0.001) (Table 2). There were 16 (15.0%)/107 patients who had damage accrual after one year of follow-up. Multivariate logistic analysis showed a tendency for achieving LLDAS during follow-up being protective for damage accrual (OR=0.27, 95%CI [0.07-1.00], p=0.050).Conclusion:In this Chinese early disease cohort, LLDAS was an attainable goal in clinical practice. Age at onset, UTP and C3 level at recruitment influenced achievement of LLDAS. LLDAS was negatively associated with disease flare and damage accrual; this needs to be confirmed by future longer follow-up.Acknowledgments:The data in this cohort was collected and recorded using the framework of the lupus low disease activity status (LLDAS) study from the Asia-Pacific Lupus Collaboration (APLC).Disclosure of Interests:Yanjie Hao: None declared, Lanlan Ji: None declared, Dai Gao: None declared, Yong Fan: None declared, Eric F. Morand Grant/research support from: AstraZeneca, Consultant of: AstraZeneca, Speakers bureau: AstraZeneca, Mandana Nikpour: None declared, Zhuoli Zhang: None declared

Is Treat-to-target in Lupus Nephritis Realistic in Clinical Practice?

2018 ◽  
Vol 15 (1) ◽  
pp. 2-6 ◽  
Author(s):  
Chi Chiu Mok
Keyword(s):  
Lupus Nephritis ◽  
Disease Activity ◽  
Safety Concern ◽  
Real Life ◽  
Current Treatment ◽  
Treat To Target ◽  
Low Disease Activity ◽  
Activity State ◽  
Definition Of ◽  
Comparative Trials

The Treat-to-Target (T2T) principle has been advocated in a number of inflammatory and non-inflammatory medical illnesses. Tight control of disease activity has been shown to improve the outcome of rheumatoid arthritis and psoriatic arthritis as compared to the conventional approach. However, whether T2T can be applied to patients with lupus nephritis is still under emerging discussion. Treatment of lupus nephritis should target at inducing and maintaining remission of the kidney inflammation so as to preserve renal function and improve survival in the longterm. However, there is no universal agreement on the definition of remission or low disease activity state of nephritis, as well as the time points for switching of therapies. Moreover, despite the availability of objective parameters for monitoring such as proteinuria and urinary sediments, differentiation between ongoing activity and damage in some patients with persistent urinary abnormalities remains difficult without a renal biopsy. A large number of serum and urinary biomarkers have been tested in lupus nephritis but none of them have been validated for routine clinical use. In real life practice, therapeutic options for lupus nephritis are limited. As patients with lupus nephritis are more prone to infective complications, tight disease control with aggressive immunosuppressive therapies may have safety concern. Not until the feasibility, efficacy, safety and cost-effectiveness of T2T in lupus nephritis is confirmed by comparative trials, this approach should not be routinely recommended with the current treatment armamentarium and monitoring regimes.

Are remission and low disease activity state ideal targets for pregnancy planning in Systemic Lupus Erythematosus? A multicentre study

Rheumatology ◽  
2021 ◽  
Author(s):  
Chiara Tani ◽  
Dina Zucchi ◽  
Isabell Haase ◽  
Maddalena Larosa ◽  
Francesca Crisafulli ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Intrauterine Fetal Death ◽  
Treat To Target ◽  
Low Disease Activity ◽  
Disease Flare ◽  
Disease Remission ◽  
Adverse Pregnancy ◽  
Activity State

Abstract Objectives To determine whether disease remission or low disease activity state at the beginning of pregnancy in SLE patients is associated with better pregnancy outcome. Methods pregnancies in SLE patients prospectively monitored by pregnancy clinics at four rheumatology centres were enrolled. Patient demographics and clinical information were collected at baseline (pregnancy visit before 8 weeks of gestation) including whether patients were in remission according to DORIS criteria and and/or Lupus Low Disease Activity State (LLDAS). Univariate and multivariate analysis were performed to determine predictors of disease flare and adverse pregnancy outcomes (APOs) including preeclampsia, preterm delivery, small for gestational age infant, intrauterine growth restriction and intrauterine fetal death. Results 347 pregnancies were observed in 281 SLE patients. Excluding early pregnancy losses, 212 pregnancies (69.7%) occurred in patients who were in remission at baseline, 33 (10.9%) in patients in LLDAS, and the remainder in active patients. 73 flares (24%) were observed during pregnancy or puerperium, and 105 (34.5%) APOs occurred. Multivariate analysis revealed that patients in disease remission or taking hydroxychloroquine were less likely to have disease flare, while a history of lupus nephritis increased the risk. The risk of APOs was increased in patients with shorter disease duration, while being on hydroxychloroquine resulted a protective variable. An almost significant association between complete remission and a decreased risk of APOs was observed. Conclusions Prenatal planning with a firm treat-to-target goal of disease remission is an important strategy to reduce the risk of disease flares and severe obstetrical complications in SLE pregnancies.

scholarly journals AB0374 LUPUS LOW DISEASE ACTIVITY STATE AND MAINTAINING DRUG THERAPY: A RETROSPECTIVE INVESTIGATION

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1487.2-1487
Author(s):  
E. Gotelli ◽  
A. Sulli ◽  
G. Ferrari ◽  
G. Pacini ◽  
C. Schenone ◽  
...  
Keyword(s):  
Disease Activity ◽  
Hemolytic Anemia ◽  
Clinical Remission ◽  
Disease Onset ◽  
Treat To Target ◽  
Research Support ◽  
Low Disease Activity ◽  
Wide Range ◽  
Target Strategy ◽  
Activity State

Background:Systemic lupus erythematosus (SLE) is a chronic autoimmune multisystemic disease, that can begin with a wide range of clinical manifestations, and requires immunosuppressive therapies (1). A treat-to-target strategy leads to a high rate of clinical remission among patients (2). Several “remission” definitions have been provided in the last years and Lupus Low Disease Activity State (LLDAS) seems one of the best tools to evaluate it in clinical practice (3).Objectives:To evaluate the prevalence of SLE signs and symptoms at onset and the drugs used to induce and maintain the clinical remission, evaluated by LLDAS, in a real-life cohort of SLE patients.Methods:Thirty female SLE patients (mean age 52±15 years; mean age at disease onset 34±16 years, mean disease duration 18±13 years) in clinical remission have been enrolled (EULAR/ACR 2019 criteria) (4). Remission was defined by LLDAS (SLEDAI-2K < 4 and no activity in major organ systems, no hemolytic anemia; no new features of activity compared with previous assessment, physician global assessment (PGA) ≤ 1, prednisone dose ≤7.5 mg/day, well tolerated and stable therapy with maintenance doses of immunosuppressive drugs). Clinical and serological manifestations, SLEDAI-2K and pharmacological treatments were recorded at baseline and during follow-up.Results:Mucocutaneous involvement (57%), arthritis (30%), serositis (30%), nephritis (27%), leukopenia (23%), thrombocytopenia (20%), hemolytic anemia (13%), antiphospholipid syndrome manifestations (16%), neuro-psychiatric lupus symptoms (6%) were present in various combinations at disease onset. Baseline mean SLEDAI-2K was 10.5±2.5. Patients were treated with different dosages of glucocorticoids (100%), hydroxychloroquine (HCQ, 73%), cyclofosfamide (20%), mycophenolate mofetile (MMF, 13%), azathioprine (AZA, 13%), methotrexate (MTX, 13%), cyclosporine A (CSA, 6%), rituximab (3%), abatacept (ABA, 3%). Glucocorticoids were prescribed together with a single DMARD in 50% of cases and with two DMARDs in the remaining 50% of patients. Patients reached LLDAS remission after a mean time of 14±12 years, with a mean remission duration of 4.2±3.2 years (mean SLEDAI-2K at last visit 1±1; Mean PGA 0.4±0.1). Maintenance therapies during remission were prednisone ≤ 5 mg/day and/or HCQ ≤ 400 mg/day and/or CSA ≤ 200 mg/day and/or MTX ≤ 10 mg/weekly and/or MMF ≤ 2 g/day and/or AZA ≤ 100 mg/day. In particular, only prednisone 7%, only HCQ 3%, prednisone + HCQ 53%, prednisone + single DMARD (different from HCQ) 7%, prednisone + HCQ + DMARDs 30%.Conclusion:After reaching the clinical remission by a treat to target strategy, the administration of low dose of prednisone and HCQ in the majority of SLE patients (63%) seems useful to prevent new SLE flares. The retrospective design and the absence of a control group of patients with active disease limit this study.References:[1]Lisnevskaia L et al. 2014.Lancet384(9957):1878-1888.[2]Van Vollenhoven RF et al. 2014.Ann Rheum Dis73(6): 958-967.[3]Franklyn K et al. 2016.Ann Rheum Dis. 75(9): 1615-21.[4]Aringer M et al. 2019.Arthritis Rheumatol.71(9): 1400-1412.Disclosure of Interests:Emanuele Gotelli: None declared, Alberto Sulli Grant/research support from: Laboratori Baldacci, Giorgia Ferrari: None declared, Greta Pacini: None declared, Carlotta Schenone: None declared, Massimo Patanè: None declared, Pietro Francesco Bica: None declared, Carmen Pizzorni: None declared, Maurizio Cutolo Grant/research support from: Bristol-Myers Squibb, Actelion, Celgene, Consultant of: Bristol-Myers Squibb, Speakers bureau: Sigma-Alpha, Sabrina Paolino: None declared

scholarly journals Attainment of treat-to-target endpoints in SLE patients with high disease activity in the atacicept phase 2b ADDRESS II study

Rheumatology ◽  
2020 ◽  
Vol 59 (10) ◽  
pp. 2930-2938 ◽  
Author(s):  
Eric F Morand ◽  
David A Isenberg ◽  
Daniel J Wallace ◽  
Amy H Kao ◽  
Cristina Vazquez-Mateo ◽  
...  
Keyword(s):  
Disease Activity ◽  
B Lymphocyte ◽  
High Disease Activity ◽  
Treat To Target ◽  
Low Disease Activity ◽  
Post Hoc Analysis ◽  
Disease Outcomes ◽  
B Lymphocyte Stimulator ◽  
Activity State ◽  
Post Hoc

Abstract Objective Low disease activity (LDA) and remission are emerging treat-to-target (T2T) endpoints in SLE. However, the rates at which these endpoints are met in patients with high disease activity (HDA) are unknown. Atacicept, which targets B lymphocyte stimulator and a proliferation-inducing ligand, improved disease outcomes in SLE patients with HDA (SLEDAI-2K ≥10) at baseline in the phase 2b ADDRESS II study. This is a post hoc analysis of T2T endpoints in these patients. Methods Patients received weekly atacicept (75 or 150 mg s.c.) or placebo for 24 weeks (1:1:1 randomization). Attainment of three T2T endpoints, LDA (SLEDAI-2K ≤ 2), Lupus Low Disease Activity State (LLDAS) and remission (clinical SLEDAI-2K = 0, prednisone-equivalent ≤5mg/day and Physician’s Global Assessment &lt;0.5), was assessed and compared with SLE Responder Index (SRI)-4 and SRI-6 response. Results Of 306 randomized patients, 158 (51.6%) had baseline HDA. At week 24, 37 (23.4%) HDA patients attained LDA, 25 (15.8%) LLDAS and 17 (10.8%) remission. Each of these endpoints was more stringent than SRI-4 (n = 87; 55.1%) and SRI-6 (n = 67; 42.4%). Compared with placebo (n = 52), at week 24, patients treated with atacicept 150 mg (n = 51) were more likely to attain LDA [odds ratio (OR) 3.82 (95% CI: 1.44, 10.15), P = 0.007], LLDAS [OR 5.03 (95% CI: 1.32, 19.06), P = 0.018] or remission [OR 3.98 (95% CI: 0.78, 20.15), P = 0.095]. Conclusion At week 24, LDA, LLDAS and remission were more stringent than SRI-4 and SRI-6 response, were attainable in the HDA population and discriminated between treatment with atacicept 150 mg and placebo. These results suggest that T2T endpoints are robust outcome measures in SLE clinical trials and support further evaluation of atacicept in SLE. Trail registration ClinicalTrials.gov, http://clinicaltrials.gov, NCT01972568.

Definition and initial validation of a Lupus Low Disease Activity State (LLDAS)

2015 ◽  
Vol 75 (9) ◽  
pp. 1615-1621 ◽  
Author(s):  
Kate Franklyn ◽  
Chak Sing Lau ◽  
Sandra V Navarra ◽  
Worawit Louthrenoo ◽  
Aisha Lateef ◽  
...  
Keyword(s):  
Disease Activity ◽  
Lupus Erythematosus ◽  
Organ Damage ◽  
Nominal Group ◽  
Systemic Lupus ◽  
Low Disease Activity ◽  
Organ Systems ◽  
Damage Accrual ◽  
Activity State ◽  
Definition Of

AimsTreating to low disease activity is routine in rheumatoid arthritis, but no comparable goal has been defined for systemic lupus erythematosus (SLE). We sought to define and validate a Lupus Low Disease Activity State (LLDAS).MethodsA consensus definition of LLDAS was generated using Delphi and nominal group techniques. Criterion validity was determined by measuring the ability of LLDAS attainment, in a single-centre SLE cohort, to predict non-accrual of irreversible organ damage, measured using the Systemic Lupus International Collaborating Clinics Damage Index (SDI).ResultsConsensus methodology led to the following definition of LLDAS: (1) SLE Disease Activity Index (SLEDAI)-2K ≤4, with no activity in major organ systems (renal, central nervous system (CNS), cardiopulmonary, vasculitis, fever) and no haemolytic anaemia or gastrointestinal activity; (2) no new lupus disease activity compared with the previous assessment; (3) a Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA)-SLEDAI physician global assessment (scale 0–3) ≤1; (4) a current prednisolone (or equivalent) dose ≤7.5 mg daily; and (5) well tolerated standard maintenance doses of immunosuppressive drugs and approved biological agents. Achievement of LLDAS was determined in 191 patients followed for a mean of 3.9 years. Patients who spent greater than 50% of their observed time in LLDAS had significantly reduced organ damage accrual compared with patients who spent less than 50% of their time in LLDAS (p=0.0007) and were significantly less likely to have an increase in SDI of ≥1 (relative risk 0.47, 95% CI 0.28 to 0.79, p=0.005).ConclusionsA definition of LLDAS has been generated, and preliminary validation demonstrates its attainment to be associated with improved outcomes in SLE.

scholarly journals Treatment targets in SLE: remission and low disease activity state

Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_5) ◽  
pp. v19-v28
Author(s):  
Vera Golder ◽  
Michel W P Tsang-A-Sjoe
Keyword(s):  
Disease Activity ◽  
Patient Outcomes ◽  
Patient Reported Outcomes ◽  
Organ Damage ◽  
Treat To Target ◽  
Low Disease Activity ◽  
Patient Reported ◽  
Target States ◽  
Activity State ◽  
Development And Validation

Abstract Treat-to-target strategies have changed the approach to management of many chronic conditions, with improvements in patient outcomes. The key to success of treat to target is the availability of validated treatment endpoints, which have been difficult to derive for SLE, a condition notorious for its heterogeneity. This review will focus on the development and validation of the definitions of remission in SLE framework and the lupus low disease activity state. Lupus low disease activity state is more attainable than remission, with a stepwise concentric relationship between the target states indicating increasing stringency. Both lupus low disease activity state and definitions of remission in SLE remission have been proven to be associated with reduction in disease flares, reduced risk of accrual of irreversible end organ damage, and improvement in patient reported outcomes. These endpoints have therefore provided the key for the development of a treat-to-target approach in clinical practice in SLE and for the design of future clinical trials.

scholarly journals Frequencies and predictors of the Lupus Low Disease Activity State and remission in treatment-naïve patients with systemic lupus erythematosus

Rheumatology ◽  
2020 ◽  
Vol 59 (11) ◽  
pp. 3400-3407
Author(s):  
Dai Gao ◽  
Yanjie Hao ◽  
Lin Mu ◽  
Wenhui Xie ◽  
Yong Fan ◽  
...  
Keyword(s):  
Disease Activity ◽  
Lupus Erythematosus ◽  
Clinical Remission ◽  
Treatment Target ◽  
Low Disease Activity ◽  
Prednisone Dose ◽  
Peking University ◽  
Treatment Naïve ◽  
Activity State

Abstract Objectives To evaluate the attainability of Lupus Low Disease Activity State (LLDAS) and definitions of remission in SLE (DORIS) in a treatment-naïve cohort of SLE. Methods LLDAS5 was defined as LLDAS with a prednisone dose ≤5 mg/day. There were four definitions in DORIS: clinical remission on treatment (RONT), complete RONT, clinical remission off treatment (ROFT) and complete ROFT. The treatment-naïve patients from Peking University First Hospital SLE cohort were enrolled. The time to each state and their annual cumulative probabilities were estimated. The frequencies of patients who achieved each component of LLDAS or DORIS during follow-up were determined. The predictors of time to each state were identified. Results A total of 218 patients were included, with a median follow-up of 4.48 years. Respectively, 190 (87.2%), 160 (73.4%), 148 (67.9%), 94 (43.1%), 23 (10.6%) and 18 (8.3%) patients achieved LLDAS, LLDAS5, clinical RONT, complete RONT, clinical ROFT and complete ROFT. The median time to LLDAS, LLDAS5, clinical RONT and complete RONT were 1.4, 2.3, 2.6 and 4.7 years, respectively. Positive anti-dsDNA, RP and anaemia were significantly associated with prolonged time to LLDAS, LLDAS5 or clinical RONT. Conclusion Our data confirmed that LLDAS is an attainable early treatment target for SLE. Though with more difficulty, RONT can be achieved in two-thirds of our patients. ROFT may not be an ideal treatment target at present as it is only attained in few patients.

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