OP0001 The lupus low disease activity state (LLDAS) definition discriminates responders in a systemic lupus erythematosus (SLE) trial: post-hoc analysis of the phase iib muse trial of anifrolumab

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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Lupus Low Disease Activity State (LLDAS) discriminates responders in the BLISS-52 and BLISS-76 phase III trials of belimumab in systemic lupus erythematosus

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2018-214427 ◽

2019 ◽

Vol 78 (5) ◽

pp. 629-633 ◽

Cited By ~ 17

Author(s):

Shereen Oon ◽

Molla Huq ◽

Vera Golder ◽

Pei Xuan Ong ◽

Eric F Morand ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Lupus Erythematosus ◽

Phase Iii ◽

Systemic Lupus ◽

Low Disease Activity ◽

Phase Iii Trials ◽

The Difference ◽

Activity State ◽

Post Hoc

ObjectiveWe evaluated the discriminant capacity of the Lupus Low Disease Activity State (LLDAS) in post-hoc analysis of data from the BLISS-52 and BLISS-76 trials of belimumab in systemic lupus erythematosus (SLE).MethodsLLDAS attainment, discrimination between belimumab and placebo arms, and the effects in subgroups with high disease activity at recruitment were evaluated at week 52 using appropriate descriptive statistics, χ2 test and logistic regression.ResultsAt week 52, for belimumab 10 mg/kg, 17.0% and 19.3% of patients who achieved a Systemic Lupus Erythematosus Responder Index-4 also attained LLDAS in BLISS-52 and BLISS-76, respectively. Significantly more patients attained LLDAS on belimumab 10 mg/kg compared with placebo (12.5% vs 5.8%, OR 2.32, p=0.02 for BLISS-52; 14.4% vs 7.8%, OR 1.98, p=0.04 for BLISS-76). In a subgroup analysis, the difference in week 52 LLDAS attainment between belimumab 10 mg/kg and placebo was greater in patients who had higher disease activity at baseline, compared with the overall group.ConclusionsLLDAS was able to discriminate belimumab 10 mg/kg from placebo in the BLISS-52 and BLISS-76 trials. Our findings support the validity of LLDAS as an outcome measure in SLE clinical trials.

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Time in remission and low disease activity state (LDAS) are associated with a better quality of life in patients with systemic lupus erythematosus: results from LUMINA (LXXIX), a multiethnic, multicentre US cohort

RMD Open ◽

10.1136/rmdopen-2019-000955 ◽

2019 ◽

Vol 5 (1) ◽

pp. e000955 ◽

Cited By ~ 4

Author(s):

Manuel Francisco Ugarte-Gil ◽

Guillermo J Pons-Estel ◽

Luis M Vila ◽

Gerald McGwin ◽

Graciela S Alarcón

Keyword(s):

Quality Of Life ◽

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Lupus Erythematosus ◽

Short Form ◽

Systemic Lupus ◽

Low Disease Activity ◽

Sf 36 ◽

Activity State

AimsTo determine whether the proportion of time systemic lupus erythematosus patients achieve remission/low disease activity state (LDAS) is associated with a better quality of life (QoL).Patients and methodsPatients from a well-established multiethnic, multicentre US cohort were included: remission: Systemic Lupus Activity Measure (SLAM) score=0, prednisone≤5 mg/day and no immunosuppressants); LDAS not in remission, SLAM score≤3, prednisone≤7.5 mg/day, no immunosuppressants; the combined proportion of time patients were in these states was the independent variable. The endpoints were the Physical and Mental Components Summary measures (PCS and MCS, respectively) and the individual subscales of the Short Form (SF)-36 at the last visit. Linear regression was used to estimate the association between the proportion of follow-up time in remission/LDAS and the SF-36 measures with and without adjustment for possible confounders.ResultsFour hundred and eighty-three patients were included. The per cent of time on remission/LDAS was associated with better QoL after adjusting for potential confounders; for the PCS the parameter estimate was 9.47 (p<0.0001), for the MCS 5.89 (p=0.0027), and for the subscales they ranged between 7.51 (p=0.0495) for mental health and 31.79 (p<0.0001) for role physical.ConclusionsThe per cent of time lupus patients stay on remission/LDAS is associated with a better QoL as measured by SF-36.

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Predictors of Remission and Low Disease Activity State in Systemic Lupus Erythematosus: Data from a Multiethnic, Multinational Latin American Cohort

The Journal of Rheumatology ◽

10.3899/jrheum.180433 ◽

2019 ◽

Vol 46 (10) ◽

pp. 1299-1308 ◽

Cited By ~ 3

Author(s):

Manuel F. Ugarte-Gil ◽

Daniel Wojdyla ◽

Guillermo J. Pons-Estel ◽

Rosana Quintana ◽

José A. Gómez-Puerta ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Lupus Erythematosus ◽

Maintenance Dose ◽

Renal Involvement ◽

Immunosuppressive Drugs ◽

Older Age ◽

Systemic Lupus ◽

Low Disease Activity ◽

Activity State

Objective.To determine the predictors of remission and low disease activity state (LDAS) in patients with systemic lupus erythematosus (SLE).Methods.Three disease activity states were defined: Remission = SLE Disease Activity Index (SLEDAI) = 0 and prednisone ≤ 5 mg/day and/or immunosuppressants (maintenance dose); LDAS = SLEDAI ≤ 4, prednisone ≤ 7.5 mg/day and/or immunosuppressants (maintenance dose); and non-optimally controlled state = SLEDAI > 4 and/or prednisone > 7.5 mg/day and/or immunosuppressants (induction dose). Antimalarials were allowed in all groups. Patients with at least 2 SLEDAI reported and not optimally controlled at entry were included in these analyses. Outcomes were remission and LDAS. Multivariable Cox regression models (stepwise selection procedure) were performed for remission and for LDAS.Results.Of 1480 patients, 902 were non-optimally controlled at entry; among them, 196 patients achieved remission (21.7%) and 314 achieved LDAS (34.8%). Variables predictive of a higher probability of remission were the absence of mucocutaneous manifestations (HR 1.571, 95% CI 1.064–2.320), absence of renal involvement (HR 1.487, 95% CI 1.067–2.073), and absence of hematologic involvement (HR 1.354, 95% CI 1.005–1.825); the use of immunosuppressive drugs before the baseline visit (HR 1.468, 95% CI 1.025–2.105); and a lower SLEDAI score at entry (HR 1.028, 95% CI 1.006–1.051 per 1-unit decrease). These variables were predictive of LDAS: older age at entry, per 5-year increase (HR 1.050, 95% CI 1.004–1.098); absence of mucocutaneous manifestations (HR 1.401, 95% CI 1.016–1.930) and renal involvement (HR 1.344, 95% CI 1.049–1.721); and lower SLEDAI score at entry (HR 1.025, 95% CI 1.009–1.042).Conclusion.Absence of mucocutaneous, renal, and hematologic involvement, use of immunosuppressive drugs, and lower disease activity early in the course of the disease were predictive of remission in patients with SLE; older age was predictive of LDAS.

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THU0298 Consensus Definition of a Low Disease Activity State in Systemic Lupus Erythematosus

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2013-eular.826 ◽

2013 ◽

Vol 72 (Suppl 3) ◽

pp. A267.1-A267 ◽

Cited By ~ 1

Author(s):

C. S. Lau ◽

M. Nikpour ◽

S. V. Navarra ◽

W. Louthrenoo ◽

A. Lateef ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Lupus Erythematosus ◽

Systemic Lupus ◽

Consensus Definition ◽

Low Disease Activity ◽

Activity State ◽

Definition Of

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176 Lupus low disease activity state: predicting organ damage accrual and cardiovascular risk in patients with systemic lupus erythematosus

10.1136/lupus-2019-lsm.176 ◽

2019 ◽

Author(s):

Harrison Lam ◽

Ruta Tesfamicael ◽

Oria Lu ◽

Ratushtar Kapadia ◽

Caroline Siegel ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Cardiovascular Risk ◽

Disease Activity ◽

Lupus Erythematosus ◽

Organ Damage ◽

Systemic Lupus ◽

Low Disease Activity ◽

Damage Accrual ◽

Activity State

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Low disease activity state in juvenile-onset systemic lupus erythematosus

Lupus ◽

10.1177/09612033211054399 ◽

2021 ◽

pp. 096120332110543

Author(s):

Kubra Ozturk ◽

Senğul Caglayan ◽

Ayse Tanatar ◽

Esra Baglan ◽

Gulcin Yener Otar ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Lupus Erythematosus ◽

Low Dose ◽

Systemic Lupus ◽

Juvenile Onset ◽

Low Disease Activity ◽

Significant Difference ◽

Activity State ◽

Dose Corticosteroid

Objectives To determine the rate of achieving The Lupus Low Disease Activity State (LLDAS) in children with systemic lupus erythematosus (SLE) for tracing pertinent treatment modalities. Methods A total of 122 juvenile-onset SLE (jSLE) patients from six pediatric rheumatology centers in Turkey were enrolled in the study. LLDAS-50 was defined as encountering LLDAS for at least 50% of the observation time. According to the achievement of LLDAS-50, clinical features, immunological profiles, and treatments of patients with jSLE have been revealed. Results LLDAS of any duration was achieved by 82% of the cohort. Although only 10.8% of the patients achieved remission, 68.9% reached LLDAS-50. A significant difference was found between patients who reached LLDAS-50 and those who did not, in terms of the time to reach low-dose corticosteroid treatment ( p = 0.002), the presence of subacute cutaneous findings ( p = 0.007), and the presence of proteinuria ( p = 0.002). Both of the groups were under similar treatment approaches. However, the number of patients being treated with corticosteroids at the last visit was found to be significantly higher in patients who achieved LLDAS-50 ( p<0.001). Conclusion Targeting LLDAS in jSLE, even with long-term, low-dose corticosteroid use, seems to be an achievable goal in clinical practice.

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