Definitions Of Remission In Systemic Lupus Erythematosus Research Articles

CD19 CAR T-Cell Therapy in Autoimmune Disease — A Case Series with Follow-up

BackgroundTreatment for autoimmune diseases such as systemic lupus erythematosus (SLE), idiopathic inflammatory myositis, and systemic sclerosis often involves long-term immune suppression. Resetting aberrant autoimmunity in these diseases through deep depletion of B cells is a potential strategy for achieving sustained drug-free remission.MethodsWe evaluated 15 patients with severe SLE (8 patients), idiopathic inflammatory myositis (3 patients), or systemic sclerosis (4 patients) who received a single infusion of CD19 chimeric antigen receptor (CAR) T cells after preconditioning with fludarabine and cyclophosphamide. Efficacy up to 2 years after CAR T-cell infusion was assessed by means of Definition of Remission in SLE (DORIS) remission criteria, American College of Rheumatology–European League against Rheumatism (ACR–EULAR) major clinical response, and the score on the European Scleroderma Trials and Research Group (EUSTAR) activity index (with higher scores indicating greater disease activity), among others. Safety variables, including cytokine release syndrome and infections, were recorded.ResultsThe median follow-up was 15 months (range, 4 to 29). The mean (±SD) duration of B-cell aplasia was 112±47 days. All the patients with SLE had DORIS remission, all the patients with idiopathic inflammatory myositis had an ACR–EULAR major clinical response, and all the patients with systemic sclerosis had a decrease in the score on the EUSTAR activity index. Immunosuppressive therapy was completely stopped in all the patients. Grade 1 cytokine release syndrome occurred in 10 patients. One patient each had grade 2 cytokine release syndrome, grade 1 immune effector cell–associated neurotoxicity syndrome, and pneumonia that resulted in hospitalization.ConclusionsIn this case series, CD19 CAR T-cell transfer appeared to be feasible, safe, and efficacious in three different autoimmune diseases, providing rationale for further controlled clinical trials. (Funded by Deutsche Forschungsgemeinschaft and others.)

Pragmatic targets for moderate/severe SLE and their implications for clinical care and trial design: sustained DORIS or LLDAS for at least 6 months is sufficient while their attainment for at least 24 months ensures high specificity for damage-free progression

ObjectivesTreatment targets in systemic lupus erythematosus (SLE) have been validated in unselected—in terms of severity—cohorts, which limits their generalisability. We assessed remission (Definition of Remission in SLE (DORIS)) and Lupus...

Nex-T TM Cluster of Differentiation 19 (CD19) Chimeric Antigen Receptor (CAR) T-Cell Therapy BMS-986353 (CC-97540): Comparative Analysis of Baseline Patient Data from Trials in Systemic Lupus Erythematosus (SLE) and Relapsed/Refractory Large B-Cell Lymphoma (R/R LBCL) Related to Manufacturability and Potential Safety

Introduction: CAR T-cell therapy is currently being evaluated in non-oncologic autoimmune diseases (Mougiakakos D et al. N Engl J Med 2021; Müller F et al. Lancet 2023). In a cohort of patients (pts) with SLE, CD19 CAR T-cell therapy resulted in B-cell depletion and treatment-free, durable remission per Definitions of Remission In SLE (DORIS), suggesting that CD19 CAR T therapy may be feasible, well-tolerated, and effective for patients with SLE (Mackensen A et al. Nat Med 2022). Baseline traits associated with greater manufacturing success and lower toxicity profiles for CAR T have been identified in hematologic oncology (Mashadi-Hossein A et al. J Clin Oncol 2023; Rytlewski J et al. J Clin Oncol 2022) including age, bone marrow function, inflammatory state, and tumor burden. Here, we compared baseline traits in pts with active SLE versus R/R LBCL to predict the potential manufacturing success and toxicity profile for the ongoing phase 1 study to evaluate the investigational NEX-T TM CAR T-cell product BMS-986353 (CC-97540) in pts with severe, refractory SLE (NCT05869955). Methods: This post hoc analysis compared 42 quantitative baseline traits between pts with active SLE from PAISLEY (NCT03252587; Morand E et al. Arthritis Rheumatol 2023) and pts with R/R LBCL from TRANSCEND (NCT02631044; Abramson J et al. Lancet 2020). Baseline traits associated with improved manufacturing success and/or lower toxicity profile for CAR T in hematologic oncology were compared (Mashadi-Hossein A et al. J Clin Oncol 2023; Rytlewski J et al. J Clin Oncol 2022). A Wilcoxon rank-sum test was used to compare pt cohorts. Data are median (95% confidence interval). Results: This analysis included 363 pts with SLE and 256 pts with R/R LBCL. Of 42 baseline traits compared, 36 had nominal P values ≤ 0.05; 33 of those were ≤ 0.001. High baseline absolute lymphocyte count (ALC), platelets (PLT), and hemoglobin (Hgb) were previously associated with both improved manufacturing success and a lower toxicity profile for CAR T; pts with SLE had higher ALC, PLT, and Hgb vs R/R LBCL (ALC: 1.15 10 9/L [1.07-1.20 10 9/L] vs 0.10 10 9/L [0.10-0.13 10 9/L], P < 0.001, Figure 1A; PLT: 239 10 9/L [232-249 10 9/L] vs 144 10 9/L [129-154 10 9/L], P < 0.001; Hgb: 128 g/L [126-130 g/L] vs 98.0 g/L [95.0-100.0 g/L], P < 0.001), which is predictive of both improved manufacturing success and potentially lower toxicity. Young baseline age and high red blood cell (RBC) counts were previously associated with improved manufacturing success, and pts with SLE were younger and had higher RBC counts vs R/R LBCL (age: 40 years [38-41 years] vs 63 years [61-64 years], P < 0.001; RBCs: 4.30 10 12/L [4.20-4.40 10 12/L] vs 3.13 10 12/L [3.05-3.20 10 12/L], P < 0.001), predicting improved CAR T manufacturing success. Baseline traits reflecting tumor burden and/or bone marrow involvement that have been previously associated with higher toxicity, such as high C reactive protein (CRP; Figure 1B), high lactate dehydrogenase (LDH), and low hematocrit (Hct), were different between pts with SLE vs R/R LBCL (CRP: 1.92 mg/L [1.60-2.48 mg/L] vs 20.0 mg/L [15.5-31.8 mg/L], P < 0.001; LDH: 184 U/L [179-191 U/L] vs 282 U/L [251-317 U/L], P < 0.001; Hct: 39.0% [39.0-40.0%] vs 29.6% [28.7-30.5%], P < 0.001), and predict potentially lower toxicity. Conclusions: Comparison of baseline pt data from trials in SLE vs R/R LBCL suggests that pts with SLE have traits that predict improved manufacturing success and lower rates/severity of common CAR T-associated toxicities such as cytokine release syndrome (CRS) and neurological events. A key difference between cohorts is the potential for high tumor burden in R/R LBCL which has been previously associated with CAR T toxicity. Our results show marked differences between cohorts for tumor burden surrogate measures (CRP, LDH, Hct), bone marrow function, inflammatory state, and age which we hypothesize may potentially lead to improved CAR T manufacturing success and lower risk of CRS and/or neurological events for patients with autoimmune disorders vs R/R LBCL. Further research is needed to understand if CAR T-cell therapy may provide a promising treatment option for pts with SLE and other autoimmune conditions. The ongoing phase 1, multicenter, open-label study will evaluate the safety, feasibility, and preliminary efficacy of BMS-986353 (CC-97540) in patients with severe, refractory SLE. Study support: Bristol Myers Squibb

Targeting DORIS Remission and LLDAS in SLE: A Review.

Remission is the established therapeutic goal for patients with systemic lupus erythematosus (SLE) and is currently defined by the widely adopted Definition Of Remission In SLE (DORIS) criteria. Attainment of remission is rare in the clinical setting, thus an alternative, pragmatic treatment target of low disease activity, as defined by the Lupus Low Disease Activity State (LLDAS), provides a less stringent and more attainable treatment goal for a wider proportion of patients compared with DORIS remission. Randomized controlled trials and real-world analyses have confirmed the positive clinical benefits of achieving either DORIS remission or LLDAS. The treat-to-target (T2T) approach utilizes practical clinical targets to proactively tailor individual treatment regimens. Studies in other chronic inflammatory diseases using the T2T approach demonstrated significantly improved clinical outcomes and quality-of-life measures compared with established standard of care. However, such trials have not yet been performed in patients with SLE. Here we review the evolution of DORIS remission and LLDAS definitions and the evidence supporting the positive clinical outcomes following DORIS remission or LLDAS attainment, before discussing considerations for implementation of these outcome measures as potential T2T objectives. Adoption of DORIS remission and LLDAS treatment goals may result in favorable patient outcomes compared with established standard of care for patients with SLE.

Impact of low disease activity, remission, and complete remission on flares following tapering of corticosteroids and immunosuppressive therapy in patients with systemic lupus erythematous: a multinational cohort study.

Targets of treatment for systemic lupus erythematosus (SLE) include the Lupus Low Disease Activity State (LLDAS), remission, and complete remission. Whether treatment can be tapered after attaining these targets and whether tapering is safer in patients in complete remission compared with LLDAS are unknown. We aimed to assess the odds of disease flares after treatment tapering in stable disease, versus continuing the same therapy. We also aimed to examine whether tapering in complete remission resulted in fewer flares or longer time to flare compared with tapering in LLDAS or remission. This multinational cohort study was conducted at 25 sites across 13 Asia-Pacific countries. We included adult patients aged 18 years or older with stable SLE who were receiving routine clinical care, had two or more visits and had attained stable disease at one or more visits. We categorised stable disease into: LLDAS (Systemic Lupus Erythematosus Disease Activity Index 2000 [SLEDAI-2K] score ≤4, Physician Global Assessment [PGA] ≤1, and prednisolone ≤7·5 mg/day); Definitions of Remission in SLE (DORIS) remission (clinical SLEDAI-2K score 0, PGA <0·5, and prednisolone ≤5 mg/day); or complete remission on therapy (SLEDAI-2K score 0, PGA <0·5, and prednisolone ≤5 mg/day). Stable disease categories were mutually exclusive. Tapering was defined as any decrease in dose of corticosteroids or immunosuppressive therapy (mycophenolate mofetil, calcineurin inhibitors, azathioprine, leflunomide, or methotrexate). Using multivariable generalised estimating equations, we compared flares (SELENA-SLEDAI Flare Index) at the subsequent visit after drug tapering. We used generalised estimating equations and Cox proportional hazard models to compare tapering attempts that had begun in LLDAS, remission, and complete remission. Between May 1, 2013, and Dec 31, 2020, 4106 patients were recruited to the cohort, 3002 (73·1%) of whom were included in our analysis. 2769 (92·2%) participants were female, 233 (7·8%) were male, and 2636 (88·1%) of 2993 with ethnicity data available were Asian. The median age was 39·5 years (IQR 29·0-50·0). There were 14 808 patient visits for patients in LLDAS, or remission or complete remission, of which 13 140 (88·7%) entered the final multivariable model after excluding missing data. Among the 9863 visits at which patients continued the same therapy, 1121 (11·4%) flared at the next visit, of which 221 (19·7%) were severe flares. Of the 3277 visits at which a patient received a tapering of therapy, 557 (17·0%) flared at the next visit, of which 120 (21·5%) were severe flares. Tapering was associated with higher odds of flare compared with continuing the same therapy (odds ratio [OR] 1·24 [95% CI 1·10-1·39]; p=0·0005). Of 2095 continuous tapering attempts, 860 (41·1%) were initiated in LLDAS, 596 (28·4%) in remission, and 639 (30·5%) in complete remission. Tapering initiated in LLDAS (OR 1·37 [95% CI 1·03-1·81]; p=0·029) or remission (1·45 [1·08-1·94]; p=0·013) had higher odds of flare in 1 year compared with complete remission. Tapering in LLDAS (hazard ratio 1·24 [95% CI 1·04-1·48]; p=0·016) or remission (1·30 [1·08-1·56]; p=0·0054) had a significantly shorter time to first flare than tapering initiated in complete remission. Attaining sustained LLDAS, remission, or complete remission for at least 6 months just before the time of taper was associated with lower odds of flare at next visit, flares in 1 year, and longer time to flare. Tapering of corticosteroids or immunosuppressive therapy in patients with stable SLE was associated with excess flares. Our findings suggest that drug tapering should be carefully considered, weighing the risks and benefits, and is best exercised in complete (clinical and serological) remission and after maintaining stable disease for at least 6 months. AstraZeneca, BMS, Eli Lily, Janssen, Merck Serono, GSK, and UCB.

Viewpoint on anifrolumab in patients with systemic lupus erythematosus and a high unmet need in clinical practice

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease characterised by unpredictable flares. Many patients with SLE are unable to achieve the recommended treatment goal of remission or the intermediate,...

Risk Assessment Model for Postpartum Venous Thromboembolism Prevention in Patients with Systemic Lupus Erythematosus.

This article assesses the application of the Royal College of Obstetricians and Gynaecologists (RCOG) venous thromboembolism (VTE) risk model on a cohort of postpartum patients with a history of systemic lupus erythematosus (SLE). This is a secondary analysis of an ongoing patient registry of women with SLE from 2016 to 2022. There were 49 SLE patients with 55 pregnancies using the Definitions of Remission in SLE (DORIS) criteria to determine SLE disease activity. RCOG risk assessment model scoring was calculated for each patient prior to and after delivery. The primary outcome was the qualification of "active SLE" by standard rheumatologic criteria and assessment of recommendations for VTE prophylaxis based on RCOG VTE risk assessment scoring. Data were analyzed using Fisher's exact test, chi-square test, and Mann-Whitney U test with significance defined as p < 0.05. In the study cohort, 34 pregnancies (61.8%) were in DORIS remission at delivery. Twenty-one pregnancies (38.2%) were not and scored 3 points on the RCOG VTE risk model. Of these pregnancies, only 19% (n = 4) were recommended for VTE prophylaxis by the obstetrical provider despite RCOG score ≥3. Only 35.7% (n = 5) of pregnancies in DORIS remission, but with 3 points for non-SLE-related VTE risk factors (n = 14), were recommended for VTE prophylaxis. Of the 20 pregnancies in remission with an RCOG score < 3 after assessing all risk factors, 15% (n = 3) were nevertheless recommended for VTE prophylaxis. No patients had a postpartum VTE regardless of therapy. These data reveal a need to improve upon providing postpartum VTE prophylaxis to SLE patients not in remission while also recognizing a diagnosis of SLE alone should not equate with active disease. Moreover, SLE patients in remission may still warrant VTE prophylaxis if other non-SLE-related risk factors are present. · Those with SLE are at increased risk for VTE postpartum.. · VTE prophylaxis should be instituted when clinically appropriate.. · Caution should be exercised in broadly assigning disease activity for SLE diagnosis only.. · This study supports VTE prophylaxis use in postpartum patients with SLE..

Risk Assessment Model for Postpartum Venous Thromboembolism Prevention in Patients with Systemic Lupus Erythematosus

Background Patients with Systemic Lupus Erythematosus (SLE) may be at increased risk for developing a venous thromboembolism (VTE), particularly in the postpartum period. The Royal College of Obstetricians and Gynaecologists (RCOG) guideline for postpartum VTE prophylaxis is often used to triage which patients should get VTE prophylaxis. In this RCOG guideline, a score ≥ 3 drives a formal recommendation for postpartum anticoagulation. RCOG is unique in its inclusion of “active SLE” as an actionable VTE risk factor (adding 3 points). We sought to determine if a cohort of postpartum patients with a known history of SLE a) qualify as having “active” SLE by standard rheumatologic criteria b) have other risk factors for VTE c) received the recommended prophylaxis based on RCOG VTE risk assessment scoring and d) had a postpartum VTE. Objective To assess the application of the RCOG venous thromboembolism (VTE) risk model on a cohort of postpartum patients with a history of Systemic Lupus Erythematosus (SLE). Study Design This is a secondary analysis of an ongoing patient registry of women with SLE from 2016-2022. There were 49 SLE patients with 55 pregnancies using Definitions of Remission in SLE (DORIS) criteria to determine SLE disease activity. RCOG risk assessment model scoring was calculated for each patient prior to and after delivery. The primary outcome was the qualification of “active SLE” by standard rheumatologic criteria and assessment of recommendations for VTE prophylaxis based on RCOG VTE risk assessment scoring. Data were analyzed using Fisher’s Exact test, chi-square test, and Mann-Whitney U test with significance defined as p&lt;0.05. Results In the study cohort, 34 pregnancies (61.8%) were in DORIS remission at delivery. Twenty-one pregnancies (38.2%) were not and scored 3 points on the RCOG VTE risk model. Of these pregnancies, only 19% (n=4) were recommended for VTE prophylaxis by the obstetrical provider despite RCOG score ≥ 3. Only 35.7% (n=5) of pregnancies in DORIS remission, but with 3 points for non-SLE related VTE risk factors (n=14), were recommended for VTE prophylaxis. Of the 20 pregnancies in remission with an RCOG score &lt; 3 after assessing all risk factors, 15% (n=3) were nevertheless recommended for VTE prophylaxis. No patients had a postpartum VTE regardless of therapy. Conclusion These data reveal a need to improve upon providing postpartum VTE prophylaxis to SLE patients not in remission while also recognizing a diagnosis of SLE alone should not equate with active disease. Moreover, SLE patients in remission may still warrant VTE prophylaxis if other non-SLE-related risk factors are present.

Remission and low disease activity in Polish patients with systemic lupus erythematosus - real-life, five-year follow-up outcomes.

Remission in systemic lupus erythematosus (SLE) or Lupus Low Disease Activity State (LLDAS) are associated with less organ damage and thus create new perspectives for effective damage-limiting treatment. The aim of this study was to assess the occurrence of remission defined by The Definition of Remission In SLE (DORIS) and of LLDAS as well as their predictors in the Polish SLE cohort. In this retrospective study data were collected on patients with SLE that achieved at least one year of DORIS remission or LLDAS and were followed up for 5 years. Clinical and demographic data were gathered; DORIS and LLDAS predictors were determined by univariate regression analysis. The full analysis set included 80 patients at baseline and 70 at follow-up. Over half of patients with SLE (39; 55.7%) fulfilled the DORIS remission criteria. In this group, 53.8% (21) of patients were in remission on-treatment and 46.1% (18) in remission off-treatment. LLDAS was fulfilled by a cohort of 43 (61.4%) patients with SLE. Among patients that achieved DORIS or LLDAS at follow-up, 77% were not treated with glucocorticoids (GCs). The most important predictors for DORIS and LLDAS off-treatment were mean SLEDAI-2K score with cut-off of ≤8.0, treatment with mycophenolate mofetil or antimalarials, and the age at disease onset above 43 years. Remission and LLDAS are achievable goals in treating SLE as over half of study patients fulfilled the DORIS remission and LLDAS criteria. The identified predictors for DORIS and LLDAS indicate the importance of effective therapy leading to reduction of GC use.

Can lupus low disease activity state predict mortality in patients with SLE?

Since 2000, our ability to measure systemic lupus erythematosus (SLE) from a diagnostic, assessment, and prognostic standpoint has advanced substantially. These advances include the incorporation of the SLE Disease Activity Index, the British Isles Lupus Assessment Group, and their composite indices in clinical trials. Additional benchmarks, such as the Definition of Remission in SLE (DORIS) framework and lupus low disease activity state (LLDAS), have been used to evaluate disease activity and attainment of remission.

Long-Term Clinical Outcome in Systemic Lupus Erythematosus Patients Followed for More Than 20 Years: The Milan Systemic Lupus Erythematosus Consortium (SMiLE) Cohort.

Tackling active disease to prevent damage accrual constitutes a major goal in the management of patients with systemic lupus erythematosus (SLE). Patients with early onset disease or in the early phase of the disease course are at increased risk of developing severe manifestations and subsequent damage accrual, while less is known about the course of the disease in the long term. To address this issue, we performed a multicentre retrospective observational study focused on patients living with SLE for at least 20 years and determined their disease status at 15 and 20 years after onset and at their last clinical evaluation. Disease activity was measured through the British Isles Lupus Assessment Group (BILAG) tool and late flares were defined as worsening in one or more BILAG domains after 20 years of disease. Remission was classified according to attainment of lupus low-disease-activity state (LLDAS) criteria or the Definitions Of Remission In SLE (DORIS) parameters. Damage was quantitated through the Systemic Lupus Erythematosus International Collaborating Clinics/American College of Rheumatology damage index (SLICC/ACR-DI). LLAS/DORIS remission prevalence steadily increased over time. In total, 84 patients had a late flare and 88 had late damage accrual. Lack of LLDAS/DORIS remission status at the 20 year timepoint (p = 0.0026 and p = 0.0337, respectively), prednisone dose ≥ 7.5 mg (p = 9.17 × 10−5) or active serology (either dsDNA binding, low complement or both; p = 0.001) were all associated with increased late flare risk. Late flares, in turn, heralded the development of late damage (p = 2.7 × 10−5). These data suggest that patients with longstanding SLE are frequently in remission but still at risk of disease flares and eventual damage accrual, suggesting the need for tailored monitoring and therapeutic approaches aiming at effective immunomodulation besides immunosuppression, at least by means of steroids.

POS0759 DOES LLDAS DEFINITION MATCH THE RHEUMATOLOGIST OPINION? THE FIRST VISIT EVALUATION OF A LONGITUDINAL SPANISH MULTICENTER STUDY TO ASSESS REASONS OF DISAGREEMENT.

BackgroundTreat to Target strategies are necessary in Systemic Lupus Erythematosus (SLE). They are difficult to establish due to the heterogeneity of the disease. The current definitions of Lupus Low Disease Activity State (LLDAS) according to the Asia Pacific Lupus Collaboration (APLC) and remission according to Definition of Remission in SLE (DORIS) 2021 are difficult to achieve and maintain over time.ObjectivesTo evaluate the concordance between the LLDAS and the clinical status according to the rheumatologist opinion and reasons of disagreement. To explore modifications in LLDAS definition that best fit with the expert´s opinion.MethodsProspective multicenter study of SLE patients (ACR 1997 Classification Criteria or clinical diagnosis by the physician) from seven Spanish Rheumatology Departments. Statistical analysis: descriptive cross-sectional (at the time of recruitment) analysis of the demographic and clinical characteristics, treatments; remission and LLDAS and the subjective evaluations of SLE activity by the rheumatologist. Analysis of the level of agreement between expert opinion and the definition of LLDAS and its modification were evaluated using Cohen’s kappa.ResultsDEMOGRAPHIC, DISEASE CHARACTERISTICS AND TREATMENTS. Five hundred and eight were included (92% women; mean age (±SD): 50.4 years (±13.7)). Mean SLEDAI-2K (±SD) was 2.84 (±3.31). A total of 406 (79.9%) patients presented SLEDAI-2K≤4. A total of 317 (74.1%) patients were on antimalarial treatment. Two hundred and twenty-two (43.7%) patients were on some type of immunosuppressive or biological therapy. More than half of patients were not taking glucocorticoids (n=310, 61%). A total of 38 patients (7.5%) were taking doses of prednisone higher than 7.5mg/day.REMISSION/LLDAS 267 (54.4%) patients were in remission and 304 (62.7%) patients were in LLDAS. According to the expert opinion of the rheumatologist, remission was the most frequent state considered (n=206, 41.6%); followed by low activity (n=153, 30.9%); serologically active (n=71, 14.3%); moderate activity (n=55, 11.1%) and high activity (n=10, 2%).AGREEMENT Overall agreement between expert opinion and the definition of LLDAS was 71.4 % with a Cohen’s kappa of 0.3. The majority of the cases (96.1%) that fulfilled the definition of LLDAS, were classified by the expert as remission, serologically active or low activity. Only 12 (3,9%) patients were classified by the expert as moderate or high activity. Of the patients that did not fulfill the definition of LLDAS, 126 out of 179 (70.4%) patients were classified by the expert as remission/low disease activity (Figure 1). The main reasons for discordance in the group that did not fulfill the definition of LLDAS were the presence of new clinical features compared to previous visit and a SLEDAI 2-K &gt;4, in 74 (58.7%) and 59 (46.8%) patients, respectively. The LLDAS adjustment that meant a significant increase in the agreement was the exclusion of the comparative features with the previous visit, with an increase in the agreement to 82.6% (95% CI: 81.61-83.96%). The modification of prednisone to 5mg/daily dose, did not represent a significant change in agreement from the original definition.Figure 1.Comparison of LLDAS and expert opinionConclusionAt a given point in time, almost two thirds of SLE patients were in remission or in LLDAS. There is a good correlation between LLDAS and the physician’s opinion, particularly for those patients who fulfill LLDAS definition. However, the agreement is not so good for patients who don’t, these being excessively classified by the physician as remission or low activity. The main LLDAS items causing this disagreement were a SLEDAI-2K &gt;4 and the appearance of different clinical manifestations from the previous evaluation. On the contrary, physician assessment by the PGA adequately fits the LLDAS definition. The modification of the LLDAS definition excluding the comparison with previous assessment increases the agreement with the expert opinion to 82.6%.Disclosure of InterestsNone declared

2022 Systemic lupus erythematosus remission in clinical practice. Message for Polish rheumatologists.

Systemic lupus erythematosus (SLE) is a complicated multiorgan disease and can lead to organ damage and increased risk of morbidity and mortality. The strategy of management while avoiding complications, especially caused by chronic glucocorticoid therapy, improves outcomes. Different definitions of the treatment goal in different configurations of lupus activity indexes have appeared over the years. In 2021 the definition of remission and recommendations for its achievement were published and it become a way to implement a treat-to-target strategy. The main goal of treatment has become DORIS (definition of remission in SLE) remission and the alternative LLDAS (low lupus disease activity state).Prolonging remission with clinical and immunological lupus activity restrictions and minimizing or stopping steroid doses reduced flares and damage accrual. The analysis and neutralization of poor prognosis predictive factors in lupus could be the most beneficial for less morbidity and mortality and better quality of life.

Flare rates and factors determining flare occurrence in patients with systemic lupus erythematosus who achieved low disease activity or remission: results from a prospective cohort study.

ObjectiveTo investigate the frequency and determinants of flare in Chinese patients with lupus, focusing on the effect of glucocorticoid (GC) tapering on flare in patients who achieved low disease activity or remission.MethodsWe collected baseline and follow-up data from all consecutive patients in a prospective lupus cohort between January 2017 and December 2020. We defined low disease activity using the lupus low disease activity status (LLDAS), applied the DORIS (Definitions of Remission in SLE) for remission criteria and then assessed flare using the SELENA-SLEDAI Flare Index.ResultsAmong a total of 185 patients enrolled, 139 exhibited low disease activity or remission with a median follow-up of 29.8 (21.2–35.2) months. The flare rates after achievement of LLDAS, clinical remission and complete remission on treatment were 0.23, 0.12 and 0.1 per patient-year, respectively. In contrast, the flare rate of patients who never achieved remission or LLDAS was 0.49 per patient-year. In patients with LLDAS or remission achievement, multivariate Cox regression analysis showed that lower C3 level at the time of first achieving LLDAS or clinical remission was an independent predictive factor for subsequent flares. Kaplan-Meier curves showed a significantly lower flare-free survival during the subsequent follow-up in patients with GC withdrawal compared with those maintained on a low dose of prednisone (≤7.5 mg/day) (HR=6.94, 95% CI 1.86 to 25.86, p=0.004). However, no significant differences in flare were observed in patients maintained on different low doses of prednisone (>5 mg/day and ≤7.5 mg/day vs >2.5 mg/day and ≤5 mg/day vs >0 mg/day and ≤2.5 mg/day) (p=0.200).ConclusionsTarget achievement significantly lowered the rate of subsequent flare, from the perspective of both stricter targets and longer period in targets. C3 level was a strong predictor of flare in patients who have achieved treatment targets. Although GC tapering to minimal doses was feasible, its withdrawal may accelerate the risk of recurrence.

Pregnancy outcomes between pregnant systemic lupus erythematosus patients with clinical remission and those with low disease activity: A comparative study.

This study aims to compare pregnancy outcomes between systemic lupus erythematosus (SLE) patients who attained clinical remission based on the Definition of Remission in SLE (DORIS) and those with lupus low disease activity based on Low Lupus Disease Activity State (LLDAS). Between January 1993 and June 2017, a total of 90 pregnancies (one twin pregnancy) from 77 patients (mean age: 26.9±4.8 years; range, 17.9 to 37.3 years) were included in the study. The clinical remission and the LLDAS groups were modified into modified clinical remission and LLDAS groups, respectively by omitting Physician Global Assessment (PGA). The clinical SLE disease activity index (cSLEDAI) score was used for LLDAS. Pregnancies in 49 patients occurred, when they were in modified clinical remission and in 57 in modified LLDAS. There was no significant difference in demographic characteristics, disease activity, or medication received at conception between the two groups. Pregnancy outcomes were similar between the modified clinical remission and the modified LLDAS groups in terms of successful pregnancy (83.67% vs. 84.21%), full-term births (38.78% vs. 38.60%), fetal losses (16.33% vs. 15.79%), spontaneous abortions (14.29% vs. 14.04%), small for gestational age infants (18.37% vs. 19.30%), low birth weight infants (42.86% vs. 40.35%), maternal complications (46.94% vs. 49.12%), and maternal flares (36.73% vs. 40.35%). The agreement of pregnancy outcomes was very high between the two groups (91.11% agreement). Pregnancy outcomes in SLE patients who achieved modified clinical remission and modified LLDAS were comparable.

Systemic Lupus Erythematosus Disease Activity Score (SLE-DAS) enables accurate and user-friendly definitions of clinical remission and categories of disease activity

ObjectivesThere is an unmet need for accurate and user-friendly definitions of systemic lupus erythematosus (SLE) disease activity and remission. We aimed to derive and validate the SLE Disease Activity Score...

Predicting lupus low disease activity state and remission in SLE: novel insights

ABSTRACT Introduction:Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with extreme heterogeneity, which sometimes may be life-threatening. Principles of treat to target (T2T) in SLE were put forward more recently, leading to better long-term survival and reduced damage accrual. Areas covered: Lupus low disease activity state (LLDAS) and remission are currently the most widely accepted principal goals of SLE-T2T recommendations. In this article, we will deliver the novel insights into the definitions of LLDAS/remission, attainability, and, most importantly, clinical predictors of LLDAS and remission in SLE. Expert opinion: Since the release of the LLDAS and the framework on definitions of remission in SLE, there has been much evidence of a correlation between target attainment or maintenance and better prognosis. In the meantime, researchers are searching for predictors of target attainment. Noteworthy, prospective randomized trials are lacking worldwide to verify the benefits of T2T in various aspects of SLE. The most essential issue is that the optimal definition of the therapeutic target for SLE remains controversial, particularly regarding the maintenance dose of prednisone, the need for immunosuppressive withdrawal, and the requirement for serologic conversion. How to implement T2T principles in clinical practice also needs further investigation.

Long-term remission in patients with systemic lupus erythematosus.

Remission has been introduced as a desirable outcome and the primary target of treatment in systemic lupus erythematosus (SLE). The purpose of this study was to identify the number of patients in remission and the long-term outcome of the disease and their predictors. Of the 379 patients in our SLE Database, a total of 193 patients fulfilled the inclusion criteria. Remission was definition according to the definitions of remission in SLE. Three levels of remission were defined, including remission on-treatment, remission off-treatment and complete remission. In addition, we have defined a sustained remission for each level of remission in which the remission should last at least 5years. During a median follow-up of 96months, remission on-treatment and off-treatment, and complete remission were obtained in 49.2%, 38.9% and 19.2% of patients, respectively. Predictors of remission on-treatment in multivariate regression analysis were adherence to therapy and remission induction during 6months after treatment. Predictors of remission off-treatment were age ≥40 at the time of analysis and remission induction during 6months after treatment. Poor outcome (SLE Damage Index ≥1) was observed in 28% of the patients. Age at disease onset <30, kidney and nervous system involvement and SLEDAI-2K≥11 at the cohort entry were the risk factors of poor outcome in multivariate analysis. However, sustained remission on-treatment had a negative association with poor outcome. Treatment with glucocorticoids, antimalarials, immunosuppressants and biologics in sequential or in combination may cause durable remission. Patients with durable remission have significantly lower organ damage.

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

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. 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. 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. 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.

Treat to target in systemic lupus erythematosus

For the first time, the European League Against Rheumatism (EULAR) recommendations for the management of systemic lupus erythematosus (SLE) include atreat to target (T2T) strategy, naming remission as the main target. The aim is to improve the long-term survival, prevent damage and optimize the health-related quality of life. Compared to rheumatoid arthritis (RA) for which the T2T approach is already widely used, establishing T2T in SLE remains challenging due to its heterogeneity and limited treatment options. The aim of this article is to outline the current status of the T2T concept for SLE and to identify challenges and particularities. A special focus is placed on the use of activity scores and the importance of steroids in targeted treatment of SLE. The use of T2T for SLE remains achallenge. With the definitions of the lupus low disease activity states (LLDAS) and the definitions of remission in SLE (DORIS) abig step forward has been taken on the road towards the ideal treatment target; however, many aspects of the "treat" remain unclear. As an example, due to alack of data there are no explicit strategies for steroid reduction although it is often mandatory to achieve the targets. The T2T also includes much more than only immunosuppressive treatment and antimalarial agents, as disease damage which has already occurred and damage due to drugs, concomitant phenomena (such as depression) and comorbidities as well as measures for secondary prophylaxis must also be included.