“…The previous analysis of our cohort found that, if >50% of the follow‐up time satisfied LLDAS, there was a 50% reduction in later organ damage . Furthermore, LLDAS has now been found to be a meaningful and discriminative end point in both primary and post hoc analyses of several SLE randomized clinical trials .The achievability of lupus low disease activity state (LLDAS) in both African Americans and Caucasian patients was demonstrated, supporting the validity of LLDAS in multiple ethnicities.African American patients with systemic lupus erythematosus (SLE) were found to take longer to achieve LLDAS.These findings point to the need to include African American patients with SLE in both clinical and pharmaceutical research, because we cannot generalize from studies from Europe and Asia.…”
Objective. Lupus low disease activity state (LLDAS) is a potential treat-to-target goal in systemic lupus erythematosus (SLE). This study determined predictors of time to reach LLDAS in a longitudinal cohort.Methods. Patients were grouped according to LLDAS status at cohort entry. Those who did not satisfy LLDAS at cohort entry were analyzed prospectively. The Kaplan-Meier approach was used to estimate the time to LLDAS. Cox regression was used to identify patient characteristics that were associated with time to LLDAS.Results. The probability of LLDAS attainment within 1 year was 52% for Caucasians, 36% for African Americans, and 33% for SLE patients with renal involvement. The median time to LLDAS was 1.1 years. In multivariable models, African American ethnicity, baseline prednisone >10 mg daily, hypocomplementemia, baseline damage, and baseline renal activity remained significant predictors of longer time to attain LLDAS, while disease duration <1 year and cutaneous activity were associated with earlier attainment.Conclusion. LLDAS is potentially attainable in the majority of SLE patients. The time to LLDAS was found to be longer in African American patients with SLE. Characteristics of African American patients with SLE, such as renal activity and hypocomplementemia, were also independent predictors of slower attainment of LLDAS. These findings point to the need to include African American patients with SLE in both clinical and pharmaceutical research.
“…The previous analysis of our cohort found that, if >50% of the follow‐up time satisfied LLDAS, there was a 50% reduction in later organ damage . Furthermore, LLDAS has now been found to be a meaningful and discriminative end point in both primary and post hoc analyses of several SLE randomized clinical trials .The achievability of lupus low disease activity state (LLDAS) in both African Americans and Caucasian patients was demonstrated, supporting the validity of LLDAS in multiple ethnicities.African American patients with systemic lupus erythematosus (SLE) were found to take longer to achieve LLDAS.These findings point to the need to include African American patients with SLE in both clinical and pharmaceutical research, because we cannot generalize from studies from Europe and Asia.…”
Objective. Lupus low disease activity state (LLDAS) is a potential treat-to-target goal in systemic lupus erythematosus (SLE). This study determined predictors of time to reach LLDAS in a longitudinal cohort.Methods. Patients were grouped according to LLDAS status at cohort entry. Those who did not satisfy LLDAS at cohort entry were analyzed prospectively. The Kaplan-Meier approach was used to estimate the time to LLDAS. Cox regression was used to identify patient characteristics that were associated with time to LLDAS.Results. The probability of LLDAS attainment within 1 year was 52% for Caucasians, 36% for African Americans, and 33% for SLE patients with renal involvement. The median time to LLDAS was 1.1 years. In multivariable models, African American ethnicity, baseline prednisone >10 mg daily, hypocomplementemia, baseline damage, and baseline renal activity remained significant predictors of longer time to attain LLDAS, while disease duration <1 year and cutaneous activity were associated with earlier attainment.Conclusion. LLDAS is potentially attainable in the majority of SLE patients. The time to LLDAS was found to be longer in African American patients with SLE. Characteristics of African American patients with SLE, such as renal activity and hypocomplementemia, were also independent predictors of slower attainment of LLDAS. These findings point to the need to include African American patients with SLE in both clinical and pharmaceutical research.
“…Mycophenolate mofetil (MMF) is a potent immunosuppressant with efficacy in renal and non-renal lupus (although not in neuropsychiatric disease) 51–53. In a recent randomised, open-label trial in extrarenal SLE, enteric-coated mycophenolate sodium (EC-MPS) was superior to AZA in achieving remission and reducing flares 54. However, its teratogenic potential (needs to be discontinued at least 6 weeks before conceiving), along with its higher cost compared with AZA or MTX, poses a limitation towards universal recommendation in women of reproductive age with non-renal manifestations.…”
Our objective was to update the EULAR recommendations for the management of systemic lupus erythematosus (SLE), based on emerging new evidence. We performed a systematic literature review (01/2007–12/2017), followed by modified Delphi method, to form questions, elicit expert opinions and reach consensus. Treatment in SLE aims at remission or low disease activity and prevention of flares. Hydroxychloroquine is recommended in all patients with lupus, at a dose not exceeding 5 mg/kg real body weight. During chronic maintenance treatment, glucocorticoids (GC) should be minimised to less than 7.5 mg/day (prednisone equivalent) and, when possible, withdrawn. Appropriate initiation of immunomodulatory agents (methotrexate, azathioprine, mycophenolate) can expedite the tapering/discontinuation of GC. In persistently active or flaring extrarenal disease, add-on belimumab should be considered; rituximab (RTX) may be considered in organ-threatening, refractory disease. Updated specific recommendations are also provided for cutaneous, neuropsychiatric, haematological and renal disease. Patients with SLE should be assessed for their antiphospholipid antibody status, infectious and cardiovascular diseases risk profile and preventative strategies be tailored accordingly. The updated recommendations provide physicians and patients with updated consensus guidance on the management of SLE, combining evidence-base and expert-opinion.
“…Recently, rates of LLDAS attainment were demonstrated to differentiate treatments in a trial comparing azathioprine and mycophenolate in nonrenal SLE. 9 Utility of a novel endpoint such as LLDAS in trials of novel therapies requires it to be attainable and to align with existing response measures, but also to offer additional information, and to allow for discrimination between active treatment and placebo. Here, we present a post-hoc analysis of a large Phase IIb SLE RCT dataset and demonstrate LLDAS utility.…”
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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