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 <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.

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.

scholarly journals POS0241 VALIDATION OF THE ANKYLOSING SPONDYLITIS DISEASE ACTIVITY SCORE WITH A QUICK QUANTITATIVE C-REACTIVE PROTEIN ASSAY (ASDAS-QCRP) IN PATIENTS WITH AXIAL SPONDYLOARTHRITIS (AXSPA): A PROSPECTIVE, NATIONAL, MULTICENTER STUDY

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 342.1-342
Author(s):  
F. Proft ◽  
J. Schally ◽  
H. C. Brandt ◽  
J. Brandt-Juergens ◽  
G. R. Burmester ◽  
...  
Keyword(s):  
Ankylosing Spondylitis ◽  
Disease Activity ◽  
Disease Activity Score ◽  
High Disease Activity ◽  
Activity Score ◽  
Inactive Disease ◽  
Treat To Target ◽  
C Reactive Protein ◽  
Low Disease Activity ◽  
Reactive Protein

Background:According to international recommendations, the Ankylosing Spondylitis Disease Activity Score (ASDAS) is the preferred score for assessing disease activity in axial spondyloarthritis (axSpA) [1]. However, routine determination of C-reactive protein (CRP) to calculate ASDAS values takes hours to days. This limits the use of ASDAS in clinical routine and clinical trials and hinders the implementation of treat-to-target approaches in axSpA. Whereas quick quantitative CRP (qCRP) tests allow CRP assessment within a few minutes. In a pilot project the performance of qCRP-based ASDAS assessment (ASDAS-qCRP) was already investigated in a single center study of 50 newly diagnosed, bDMARD-naïve axSpA patients with promising results [2].Objectives:To validate the ASDAS-qCRP in a prospective, multicenter study of axSpA patients in a typical axSpA cohort with an appropriate sample size.Methods:The study was conducted in five centers in Germany. Consecutive adult (≥ 18 years) axSpA patients were included. In addition to a rheumatological assessment, including patient reported outcomes (PROs), routine CRP and erythrocyte sedimentation rate (ESR) were measured in the local labs. Additionally, a qCRP testing with the „QuikRead go instrument“ (Aidian Oy, Finland) was performed at the study center (measurement range 0.5 - 200 mg/l for hematocrit concentrations of 40 – 45%). Statistical analysis included descriptive statistics, cross tabulation and weighted Cohen´s kappa comparing disease activity categories, Bland-Altman plots and intraclass correlation coefficient (ICC) for ASDAS-CRP and ASDAS-qCRP.Results:In this study 251 axSpA patients were included between January and September 2020 (mean age: 38.4 years; mean disease duration: 6.2 years, 159 patients (63.3%) were male, 211 (84.1%) HLA-B27 positive and 195 (77.7%) were classified as radiographic axSpA). 143 patients (57.0%) were treated with bDMARDs. CRP and qCRP showed mean values of 2.12 and 2.17 mg/l, respectively. With the ASDAS-qCRP, 242 patients (96.4%) were assigned to the same disease activity category as compared to the ASDAS based on the conventional lab CRP measurement (Table 1). Weighted Cohen´s kappa was 0.966 (95%CI: 0.943; 0.988). ICC for ASDAS-CRP- and ASDAS-qCRP-values was 0.997 (95%CI: 0.994; 0.999). The agreement of ASDAS-qCRP and ASDAS-CRP is shown in a Bland-Altman plot (Figure 1).Table 1.Disease activity categories by ASDAS-qCRP vs. ASDAS-CRPASDAS-qCRP (n = 251)Inactive Disease(< 1.3)Low Disease Activity (1.3 - < 2.1)High Disease Activity (2.1 - 3.5)Very high Disease Activity (> 3.5)ASDAS-CRPInactive Disease(< 1.3)56 (22.3%)2 (0.8%)Low Disease Activity (1.3 - < 2.1)62 (24.7%)7 (2.8%)High Disease Activity (2.1 - 3.5)97 (38.6%)Very high Disease Activity (> 3.5)27 (10.8%)The fields highlighted in red indicate that disease activity categories do not match.ASDAS = Ankylosing Spondylitis Disease Activity Score, CRP = C-reactive protein, qCRP = quick quantitative CRPConclusion:The ASDAS-qCRP and ASDAS-CRP showed an almost perfect agreement on the assignment to disease activity categories (96%) with the important advantage of time. With ASDAS-qCRP, rheumatologists could base their clinical decision-making on a disease activity measurement by using a composite score immediately. ASDAS-qCRP, therefore, can be integrated in clinical routine and clinical trials in the future and may facilitate implementation of the treat-to-target concept in axial SpA.References:[1]Smolen JS, et al. Ann Rheum Dis. 2018 Jan; 77(1):3-17.[2]Proft F, et al. Joint Bone Spine. 2019 Jul 29.Figure 1.Bland-Altman plot for ASDAS-qCRP and ASDAS-CRPAcknowledgements:The authors would like to deeply thank Braun T, Doerwald C, Deter N, Höppner C, Lackinger J, Lorenz C, Lunkwitz K, Mandt B, Sron S and Zernicke J for their practical support and coordinating the study.Funding statement: The AQUA study was supported by an unrestricted research grant from Novartis. Testing kits were provided free of charge from Aidian Oy, Finland.Disclosure of Interests:None declared

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 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 Lupus Low Disease Activity State (LLDAS) attainment discriminates responders in a systemic lupus erythematosus trial: post-hoc analysis of the Phase IIb MUSE trial of anifrolumab

2018 ◽  
Vol 77 (5) ◽  
pp. 706-713 ◽  
Author(s):  
Eric F Morand ◽  
Teodora Trasieva ◽  
Anna Berglind ◽  
Gabor G Illei ◽  
Raj Tummala
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Activity Index ◽  
Controlled Trial ◽  
Systemic Lupus ◽  
Low Disease Activity ◽  
Link Type ◽  
Activity State ◽  
Post Hoc

ObjectivesIn a post-hoc analysis, we aimed to validate the Lupus Low Disease Activity State (LLDAS) definition as an endpoint in an systemic lupus erythematosus (SLE) Phase IIb randomised controlled trial (RCT) (MUSE [NCT01438489]) and then utilize LLDAS to discriminate between anifrolumab and placebo.MethodsPatients received intravenous placebo (n=102) or anifrolumab (300 mg, n=99; 1,000 mg, n=104) Q4W plus standard of care for 48 weeks. LLDAS attainment (SLE Disease Activity Index 2000 ≤4 without major organ activity, no new disease activity, Physician’s Global Assessment ≤1, prednisolone ≤7.5 mg/d and standard immunosuppressant dosage tolerance) was assessed. Associations with endpoints and LLDAS attainment differences between treatments were explored.ResultsLLDAS attainment at Week 52 was associated with SLE Responder Index 4 (SRI[4]) and British Isles Lupus Assessment Group–based Composite Lupus Assessment (BICLA) (74/85[87%] and 62/84[74%] were also SRI[4] and BICLA responders, respectively; both nominal p<0.001). Only 74/159 (47%) of SRI(4) and 62/121 (51%) of BICLA responders reached LLDAS.Anifrolumab-treated patients achieved earlier LLDAS, and more spent at least half their observed time in LLDAS (OR vs. placebo; 300 mg: 3.04, 95% CI 1.34 to 6.92, nominal p=0.008; 1,000 mg: 2.17, 95% CI 0.93 to 5.03, nominal p=0.072) vs placebo-treated patients. At Week 52, 17/102 (17%), 39/99 (39%) and 29/104 (28%) of patients on placebo, anifrolumab 300 and 1,000 mg, respectively, attained LLDAS (OR vs. placebo; 300 mg: 3.41, 95% CI 1.73 to 6.76, p<0.001; 1,000 mg: 2.03, 95% CI 1.01 to 4.07, nominal p=0.046).ConclusionsLLDAS attainment represents a clinically meaningful SLE outcome measure, and anifrolumab is associated with more patients who met LLDAS criteria versus placebo. These data support LLDAS as an SLE RCT endpoint.Trial registration numberNCT1438489; Post-results.

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