First validation of the childhood lupus low disease activity state (cLLDAS) definition in a real-life longitudinal cSLE cohort.

OBJECTIVES: To validate the childhood lupus low disease activity state (cLLDAS) definition in cSLE by describing differences in time to reach first adult LLDAS (aLLDAS) versus cLLDAS. Secondly, to analyse positive and negative predictors for maintaining cLLDAS for at least 50% of follow-up time (cLLDAS-50) and for the occurrence of damage. METHODS: Prospective longitudinal data from a cSLE cohort were analysed. Used definitions were: aLLDAS according to Franklyn, cLLDAS by cSLE treat-to-target (T2T) Task Force, disease activity score by SLEDAI -2 K and damage by SLICC damage index. RESULTS: Fifty cSLE patients were studied, with a median follow-up of 3.1 years. Each patient reached aLLDAS and cLLDAS at least once. Mean time to reach first aLLDAS/cLLDAS was 8.2/9.0 months, respectively. For 22/42 patients the mean steroid-dose related delay to reach first cLLDAS was 6.2 months. 58% of patients were able to maintain cLLDAS-50. Time to first cLLDAS (OR 0.8, p = 0.013) and higher number of flares (OR 0.374, p = 0.03) were negative predictors to maintain cLLDAS-50. Damage occurred in 34% of patients (23.5% steroid-related), in 64.7% within one year after diagnosis. African/Afro-Caribbean ethnicity, neuropsychiatric involvement and ever use of a biologic were significant predictors for damage. CONCLUSION: Time to reach cLLDAS in cSLE differs from time to (a)LLDAS, which validates the new cLLDAS definition. Attaining cLLDAS-50 was difficult in real-life. This cohort shows the high risk for early damage in cSLE. T2T with earlier focus on steroid-tapering and starting steroid-sparing drugs seems important to prevent (steroid-related) damage in cSLE.

Efficacy Of Baricitinib in Patients With Moderate-To-Severe Rheumatoid Arthritis Up to 6.5 Years Of Treatment: Results Of A Long-Term Study.

OBJECTIVES: To evaluate the long-term efficacy of once-daily baricitinib 4 mg or 2 mg in patients with active rheumatoid arthritis who had inadequate response (IR) to MTX, csDMARDs, or bDMARDs. METHODS: Data from three completed phase III studies, RA-BEAM (MTX-IR), RA-BUILD (csDMARD-IR), and RA-BEACON (bDMARD-IR), and one completed long-term extension study (RA-BEYOND) were analyzed up to 6.5 years (340 weeks [RA-BEAM] and 336 weeks [RA-BUILD and RA-BEACON]). Low disease activity (LDA) (Simplified Disease Activity Index [SDAI] ≤11), clinical remission (SDAI ≤3.3), and physical function (Health Assessment Questionnaire Disability Index [HAQ-DI] ≤0.5) were the main outcomes assessed. Completer and non-responder imputation (NRI) analyses were conducted on each population. RESULTS: At week 340 or 336, LDA was achieved in 37%/83% of MTX-IR, 35%/83% of csDMARD-IR, and 23%/73% of bDMARD-IR patients treated with baricitinib 4 mg, assessed by NRI/completer analyses, respectively. Remission was achieved in 20%/40% of MTX-IR, 13%/32% of csDMARD-IR, and 9%/30% of bDMARD-IR patients treated with baricitinib 4 mg, assessed by NRI/completer analyses, respectively. HAQ-DI ≤0.5 was reached in 31%/51% of MTX-IR, 25%/46% of csDMARD-IR, and 24%/38% of bDMARD-IR patients treated with baricitinib 4 mg, assessed by NRI/completer analyses, respectively. CONCLUSION: Treatment with baricitinib 4 mg or 2 mg demonstrated efficacy up to 6.5 years with maintained LDA/remission results across SDAI, CDAI and DAS28-hsCRP consistent with previously reported data, and was well tolerated.

Lupus Low Disease Activity State and organ damage in relation to quality of life in systemic lupus erythematosus: a cohort study with up to 11 years of follow-up.

OBJECTIVES: Beyond prevention of organ damage, treatment goals in systemic lupus erythematosus (SLE) include optimisation of health-related quality of life (HRQoL). The Lupus Low Disease Activity State (LLDAS) has received increasing attention as a goal whenever remission cannot be achieved. How SLE disease activity, organ damage, and LLDAS attainment relate to patient-reported outcomes (PROs) is not fully explored, which formed the scope of this investigation. METHODS: We included 327 patients with SLE from a tertiary referral centre. Longitudinal registrations of disease activity using SLEDAI-2K and physician global assessment (PhGA), organ damage using the SLICC/ACR damage index (SDI), pharmacotherapies, EQ-5D-3L data, as well as visual analogue scale (VAS) scores for fatigue, pain, and overall SLE-related health state over a median follow-up time of 8.5 years were analysed. RESULTS: In the overall population, as well as subgroups of patients with recent-onset SLE and those with clinically active, autoantibody-positive disease, LLDAS attainment, lower PhGA, and lower clinical SLEDAI-2K scores were associated with favourable HRQoL by EQ-5D-3L and VAS assessments, while increasing SDI scores were associated with poor PROs yet not fatigue in the overall population. PROs were further enhanced by being in LLDAS sustainedly. In fully adjusted models of the entire study population, LLDAS attainment and lower disease activity were associated with favourable PROs, irrespective of SDI. CONCLUSION: In one of the longest to date observational studies, we demonstrated that low disease activity and being sustainedly in LLDAS were coupled with favourable HRQoL, pain, fatigue, and overall health experience, irrespective of organ damage.

[Low disease activity and remission status of systemic lupus erythematosus in a real-world study].

OBJECTIVE: To investigate the rates of low disease activity and clinical remission in patients with systemic lupus erythematosus (SLE) in a real-world setting, and to analyze the related factors of low disease activity and clinical remission. METHODS: One thousand patients with SLE were enrolled from 11 teaching hospitals. Demographic, clinical and laboratory data, as well as treatment regimes were collec-ted by self-completed questionnaire. The rates of low disease activity and remission were calculated based on the lupus low disease activity state (LLDAS) and definitions of remission in SLE (DORIS). Charac-teristics of patients with LLDAS and DORIS were analyzed. Multivariate Logistic regression analysis was used to evaluate the related factors of LLDAS and DORIS remission. RESULTS: 20.7% of patients met the criteria of LLDAS, while 10.4% of patients achieved remission defined by DORIS. Patients who met LLDAS or DORIS remission had significantly higher proportion of patients with high income and longer disease duration, compared with non-remission group. Moreover, the rates of anemia, creatinine elevation, increased erythrocyte sedimentation rate (ESR) and hypoalbuminemia was significantly lower in the LLDAS or DORIS group than in the non-remission group. Patients who received hydroxychloroquine for more than 12 months or immunosuppressant therapy for no less than 6 months earned higher rates of LLDAS and DORIS remission. The results of Logistic regression analysis showed that increased ESR, positive anti-dsDNA antibodies, low level of complement (C3 and C4), proteinuria, low household income were negatively related with LLDAS and DORIS remission. However, hydroxychloroquine usage for longer than 12 months were positively related with LLDAS and DORIS remission. CONCLUSION: LLDAS and DORIS remission of SLE patients remain to be improved. Treatment-to-target strategy and standar-dized application of hydroxychloroquine and immunosuppressants in SLE are recommended.

Post hoc analysis of patients with rheumatoid arthritis under clinical remission in two Japanese Phase 3 trials of peficitinib treatment (RAJ3 and RAJ4).

OBJECTIVE: We evaluated remission rates and their relationship with baseline characteristics in patients with rheumatoid arthritis treated with the oral Janus kinase inhibitor peficitinib. METHODS: This post hoc analysis of data from two Phase 3 studies (RAJ3 and RAJ4) of peficitinib (100 and 150 mg/day) in Asian rheumatoid arthritis patients investigated clinical disease activity index (CDAI) remission and low disease activity rates from baseline to Week 52. CDAI, Health Assessment Questionnaire-Disability Index, and van der Heijde-modified total Sharp score remission/low disease activity rates at Week 52 were evaluated among patients achieving CDAI remission at Weeks 12/28. Logistic regression analyses explored the relationship between baseline characteristics and CDAI remission/low disease activity rates. RESULTS: CDAI remission rates increased over time in a dose-dependent manner in both peficitinib-treated groups. Most patients achieving CDAI remission at Weeks 12/28 also achieved remission at Week 52. Following the multivariate analysis of demographic and baseline characteristics, factors associated with the achievement of CDAI remission at Week 28 included male sex, low baseline prednisone dose (RAJ3 only), and low baseline Disease Activity Score 28-C-reactive protein (RAJ4 only). CONCLUSIONS: Peficitinib demonstrated persistent efficacy in clinical remission to Week 52. Baseline characteristics associated with CDAI remission were mostly consistent with previous studies using other disease-modifying antirheumatic drugs.

Intensive treatment for the progression of joint damage in rheumatoid arthritis patients with low disease activity or remission.

OBJECTIVES: To investigate the effects of intensive treatment on joint damage in patients with rheumatoid arthritis (RA) showing progression of joint damage and low disease activity or remission. METHODS: Eighty-nine patients who had change in the van der Heijde modified total Sharp score (TSS) of >0.5 points at baseline when compared with the score 1 year ago were enrolled and categorized into two groups to receive intensive (intensive group) or current (current group) treatment. The intensive and current groups were compared for change (Δ) from baseline to 1 year of erosion score, joint space narrowing score, and TSS. RESULTS: The ΔTSS values at 1 year in the intensive and current groups were 0.67 ± 1.09 and 1.79 ± 1.70, respectively (P < 0.001). In the intensive and current groups, the ΔTSS ≤ 0.5 at 1 year were 66.7% and 32.4%, respectively (P = 0.010). CONCLUSIONS: The intensive treatment was more effective at suppressing joint damage than the current treatment. The progression of joint damage is an important target to consider for intensive treatment.

PReS-endorsed international childhood lupus T2T task force definition of childhood lupus low disease activity state (cLLDAS).

OBJECTIVE: To achieve a consensus-based definition of Low Disease Activity (LDA) for use in cSLE trials. METHODS: The International cSLE T2T Task Force, comprising of paediatric rheumatologists/nephrologists, and adult rheumatologists undertook a series of Delphi surveys/consensus meetings to discuss, refine, and vote upon cSLE LDA criteria. RESULTS: The Task Force agreed that LDA should be based upon the adult-SLE Lupus Low Disease Activity State definition (LLDAS), with modifications to make it applicable to cSLE (cLLDAS). They agreed upon five cLLDAS criteria: (1) SLE Disease Activity Index (SLEDAI)-2 K ≤4, with no activity in major organ systems; (2) no new features of lupus disease activity compared with the last assessment; (3) Physician Global Assessment score of ≤1 (0-3 scale); (4) prednisolone dose of ≤0.15 mg/kg/day, 7.5 mg/day/maximum; while on (5) stable antimalarials, immunosuppressives, and biologics. CONCLUSIONS: A cSLE-appropriate definition of cLLDAS has been generated, maintaining alignment with the adult-SLE definition to promote life-course research.

Predictors and prognostic stratification for lupus low disease activity state: results from a prospective clinical trial.

OBJECTIVE: To identify predictors for lupus low disease activity state (LLDAS), early-achieved LLDAS and long-term disease activity, and to refine a prognostic stratification tool for use in active SLE patients. METHOD: A total of 245 active SLE patients were enrolled, followed up quarterly from 2014 to 2016. LLDAS-50 was defined as the maintenance of LLDAS for ≥50% of the observed time. LLDAS at 3 months after cohort entry (LLDAS-3mo) was considered an early-achieved LLDAS. Multivariate analysis was performed to identify predictors for LLDAS, early-achieved LLDAS and long-term disease activity. Based on the factors associated with LLDAS, a prognostic stratification tool for LLDAS was established. RESULTS: The 2-year probability of achieving LLDAS was 62.9% (154/245). Multivariate analysis-determined renal involvement, haematological involvement and hypocomplementaemia were negative predictors for achieving LLDAS and LLDAS-50. In multivariate logistic analysis, antiphospholipid antibodies positivity, hypocomplementaemia, renal involvement and haematological involvement were identified as negative predictors for achieving LLDAS-3mo. LLDAS-3mo (P < 0.0001; risk ratio: 47.694; 95% CI: 13.776, 165.127) was a strong predictor for LLDAS-50. The probability of achieving LLDAS, LLDAS-50 and LLDAS-3mo were 88.9% (32/36), 69.4% (25/36) and 41.7% (15/36) in the low-risk group, 65% (65/100), 51.0% (51/100) and 32.0% (32/100) in intermediate-risk group, and 52.8% (57/108), 27.8% (30/108) and 13.0% (14/108) in high-risk group respectively. Significant differences (P < 0.0001) were observed in the LLDAS Kaplan-Meier estimates for the three risk groups based on the identified risk factors. CONCLUSION: Renal involvement, haematological involvement and hypocomplementaemia were negative predictors of LLDAS achievement and maintenance. LLDAS-3mo was a positive predictor for the long-term sustainment of LLDAS.

Grit personality of physicians and achievement of treatment goals in patients with system lupus erythematosus.

OBJECTIVES: Although personality characteristics of patients with SLE affect their disease activity and damage, it is unclear whether those of attending physicians affect the outcomes of patients with SLE. Grit is a personality trait for achieving long-term goals that may influence the decision-making for continuing treatment plans for patients. We aimed to evaluate the relationship between the grit of attending physicians and achievement of treatment goals in patients with SLE. METHODS: This cross-sectional study was conducted at five referral hospitals. The main exposure was 'consistency of interest' and 'perseverance of effort' of the attending physicians, measured by the Short Grit Scale. The primary outcome was achievement of a lupus low disease activity state (LLDAS). The association between physicians' grit score and LLDAS was analysed by generalized estimating equation (GEE) logistic regression with cluster robust variance estimation, with adjustment for confounders. RESULTS: The median (interquartile range) total, consistency and perseverance scores of 37 physicians were 3.1 (2.9-3.6), 3.3 (2.8-3.8) and 3.3 (3.0-3.5), respectively. Among the 386 patients, 154 (40%) had achieved LLDAS. Low consistency score (≤2.75) in physicians was related to LLDAS achievement independently using GEE logistic regression. The score of the question 'I often set a goal but later choose to pursue a different one' was significantly higher in patients achieving LLDAS. CONCLUSIONS: Difficulty of attending physicians to change treatment goals might be related to lower LLDAS achievement in patients with SLE.

Evaluation of belimumab in treatment of Chinese childhood-onset systemic lupus erythematosus: a prospective analysis from multicenter study.

OBJECTIVE: The aim of this study is to identify whether low lupus disease activity status (LLDAS) and clinical remission (CR) of belimumab plus standard of care (SoC) therapy are achievable goals in childhood-onset SLE (cSLE). METHODS: This multicentre, one arm pre-post intervention study was conducted at 15 centers in China. The primary end point was to describe the proportion of patients who achieved LLDAS and CR after 3, 6, and 12 months after treatment with belimumab plus SoC therapy. A multiple regression model was used to impute missing data. A Poisson regression model was used to calculate the effect of belimumab treatment on the reduced risk of serious diseases and the incidence of new damage. RESULT: 193 (92.2% female) with active cSLE from 15 centers were included. At 3, 6 and 12 months, the proportion of LLDAS (CR) was 12.4% (1.0%), 25.6% (4.5%) and 70.3% (29.7%), respectively. The mean SELENA-SLEDAI score decreased from 11.0 at baseline to 3.7, 2.9 and 1.7 at 3, 6, and 12 months. At baseline, all patients received steroids at a mean (SD) prednisone equivalent dose of 31.0 (18.2) mg/day, which decreased to 19.4 (10.8) mg/day at month 3, 12.6 (7.2) mg/day at month 6 and 6.7 (5.3) mg/day at month 12. The symptoms and immunological indicators were also significantly improved. CONCLUSION: This is the first and largest sample size prospective clinical intervention study of cSLE patients treated with belimumab in China. LLDAS and CR were attainable treat-to-target of belimumab plus SoC therapy in cSLE.

Low disease activity state associated with fewer incident vertebral fractures in Mestizo women with systemic lupus erythematosus.

BACKGROUND: Low disease activity state (LDAS) has been linked to a significant reduction in flares and damage accrual in patients with systemic lupus erythematosus (SLE); however, the effect of LDAS on the risk of vertebral fractures (VFs) in subjects with SLE is unknown, considering that low bone mineral density (BMD) and VF are frequent in SLE. OBJECTIVE: to evaluate whether achieving LDAS ≥50% of the observation time prevents new VF and BMD changes in Mestizo women. METHODS: We carried out a longitudinal, observational, and retrospective study. Mestizo women with SLE were included for a median of an 8-year follow-up. LDAS was described as Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score ≤4, prednisone ≤7.5 mg/day, and stable immunosuppressive therapies. BMD measurements and lateral thoracic and lumbar radiographs for a semiquantitative analysis for VF were assessed at baseline and during the follow-up. Uni- and multivariable interval-censored survival regression models were carried out. RESULTS: We included 110 patients: 35 (31.8%) had new VF. A total of 56 patients (50.1%) achieved LDAS ≥50% of the time during the follow-up and achieved a significantly lesser risk of incident VF (HR = 0.16; 95% CI, 0.06-0.49). After adjusting by age, BMI, menopause, prevalent VF, baseline BMD, cumulative glucocorticoid use, and anti-osteoporotic therapy, LDAS-50 was significantly related to a decrease in the risk of a new VF (HR = 0.39; 95% CI, 0.16-0.98). There was no association between LDAS and BMD measurement changes. When only patients on LDAS but not in remission (n = 43) were evaluated for the risk of incident VF, both uni- and multivariate analyses were significant (HR = 0.12; 95 CI, 0.04-47; p = 0.001, and HR = 0.26; 95% CI, 0.7-0.88; p = 0.03). CONCLUSIONS: LDAS ≥50% of the time was significantly associated with a diminished risk of new VF in Mestizo women with SLE, even in patients not in remission. However, LDAS did not help modify BMD changes over time.

Treat-to-Target in Pediatric Rheumatic Diseases.

PURPOSE OF REVIEW: To summarize the current evidence on the adoption of the treat-to-target (T2T) strategy in pediatric rheumatic diseases (PRD). RECENT FINDINGS: The recent advances in the management of PRD have markedly increased the ability to achieve disease remission. Complete disease quiescence is regarded as the ideal therapeutic goal because its attainment leads to lesser long-term damage and physical disability, and to optimization of quality of life. Studies in adult rheumatic diseases have shown that patient outcomes are improved if complete suppression of the inflammatory process is aimed for by frequent adjustments of therapy according to quantitative indices. This approach, which underlies the T2T concept, has been applied in strategic trials in rheumatoid arthritis (RA). Furthermore, recommendations for the T2T have been issued for RA and other adult rheumatic diseases. There is currently a growing interest for the introduction of T2T in PRD, and recommendations for treating juvenile idiopathic arthritis (JIA) to target were promulgated. A similar initiative has been undertaken for childhood-onset systemic lupus erythematosus. Preliminary therapeutic studies have explored the T2T design in JIA. The T2T strategy is a modern therapeutic approach that holds the promise of improving the outcomes in patients with PRD.

Lupus low disease activity state as a treatment target for pediatric patients with lupus nephritis.

BACKGROUND: Lupus low disease activity state (LLDAS) is a treatment target for patients with SLE and is associated with decreased risk for severe flare and new damage. We investigated the utility of the achievement of LLDAS in children with lupus nephritis and whether attainment of LLDAS is associated with more favorable outcomes. METHODS: Data of children, diagnosed with biopsy-proven lupus nephritis between January 2012 and December 2020, were retrospectively analyzed. RESULTS: For patients who did not achieve LLDAS after initial treatment (first 6 months), presence of autoimmune hemolytic anemia (62% vs. 18%, p = 0.047), anti-Sm (85% vs. 18%, p = 0.003) and anti-dsDNA (77% vs. 27%, p = 0.038) antibodies, proliferative lupus nephritis (77% vs. 27%, p = 0.038), and hypertension (69% vs. 9%, p = 0.005) at onset were more frequently encountered. Also, a lower rate of complete kidney response (43% vs. 100%, p = 0.005) and a higher rate of hypertension (86% vs. 13%, p = 0.002) were observed in patients who did not achieve LLDAS-50, defined as being in LLDAS at least 50% of the observation time. Attainment of both LLDAS after initial treatment and LLDAS-50 were associated with lower rates of kidney flare (p = 0.001 and p = 0.002, respectively) and damage accrual (p = 0.007 and p = 0.02, respectively) through the observation period. CONCLUSIONS: LLDAS is an attainable treatment target for children with lupus nephritis and associated with lower rates of kidney flare and damage. Presence of hematologic involvement, hypertension, and proliferative lupus nephritis at onset adversely influenced the early achievement of LLDAS. A higher resolution version of the Graphical abstract is available as Supplementary information.

Relative Remission and Low Disease Activity Rates of Tofacitinib, Baricitinib, Upadacitinib, and Filgotinib versus Methotrexate in Patients with Disease-Modifying Antirheumatic Drug-Naive Rheumatoid Arthritis.

BACKGROUND: The relative efficacy of Janus kinase (JAK) inhibitors in producing remission and low disease activity (LDA) states remains unknown since there are currently no trials that provide direct comparisons among JAK inhibitors in disease-modifying antirheumatic drug (DMARD)-naive patients with rheumatoid arthritis (RA). OBJECTIVES: This study aimed to assess the relative remission and LDA rates of tofacitinib, baricitinib, upadacitinib, and filgotinib compared to those of methotrexate (MTX) in DMARD-naive patients with RA. METHOD: We conducted Bayesian network meta-analysis and included information from direct and indirect comparisons from randomized controlled trials that examined remission (Disease Activity Score in 28 Joints using C-reactive protein level [DAS28-CRP] <2.6) and LDA (DAS28-CRP ≤ 3.2) produced by tofacitinib, baricitinib, upadacitinib, filgotinib monotherapy, and MTX in patients with DMARD-naive RA. RESULTS: Four randomized controlled trials, comprising 2,185 patients, met the inclusion criteria. This network meta-analysis showed that treatment with tofacitinib, baricitinib, upadacitinib, and filgotinib achieved a significantly higher remission rate than that with MTX (odds ratio [OR] = 4.13, 95% CI = 2.88-6.02; OR = 2.12, 95% CI = 1.17-4.13; OR = 1.95, 95% CI = 1.10-3.50; OR = 1.79, 95% CI = 1.27-3.53). The ranking probability based on the surface under the cumulative ranking curve indicated that upadacitinib 15 mg had the highest probability of achieving remission (SUCRA = 0.985), followed by tofacitinib 5 mg (SUCRA = 0.574), baricitinib 4 mg (SUCRA = 0.506), filgotinib 200 mg (SUCRA = 0.431), and MTX (SUCRA = 0.004). Moreover, treatment with tofacitinib, baricitinib, upadacitinib, and filgotinib achieved significantly higher LDA rate than that with MTX. The ranking probability for LDA was similar to that for remission; upadacitinib 15 mg had the highest probability of achieving LDA, followed by tofacitinib 5 mg, baricitinib 4 mg, filgotinib 200 mg, and MTX. CONCLUSIONS: Upadacitinib seems to be one of most effective interventions for achieving remission and LDA in DMARD-naive patients with RA based on the comparative analysis, and there are differences in remission and LDA rates induced by different JAK inhibitors.

Epstein-Barr Virus Reactivation as a New Predictor of Achieving Remission or Lupus Low Disease Activity State in Patients with Systemic Lupus Erythematosus with Cutaneous Involvement.

Although Epstein-Barr virus (EBV) reactivation has long been associated with the pathogenesis of systemic lupus erythematosus (SLE), many aspects of this relationship remain unclear. Our objective was to investigate the association between EBV reactivation and the achievement of SLE remission and lupus low disease activity state (LLDAS) over a six-month period. Clinical, laboratory, and virological tests (anti-EBV antibodies and EBV DNA) were performed among 51 patients with the active form of SLE on two occasions six months apart. SLE remission and LLDAS achievement were assessed at the end of the follow-up period. Active EBV infection was detected in 45% of active SLE patients at baseline, and 77% transitioned to latent EBV infection at six months (p < 0.001). Multivariate regression revealed a higher titer of anti-EA(D) IgM-Abs and the presence of anti-EA(D) IgM-Abs as independent predictors of remission and LLDAS in SLE patients with mucocutaneous manifestations (p = 0.042) and rash only (p = 0.023), respectively. Since a higher C3 level was an independent predictor of transition to latent EBV infection (p = 0.027), the estimated cut-off value that could identify active SLE patients who will transition to latent EBV infection after six months was ≥0.780 g/L with a sensitivity of 70.6% and a specificity of 75.0% (AUC = 0.756, p = 0.003). EBV reactivation is common in patients with active SLE, and most of them transition to latent EBV infection after six months. Achieving remission and LLDAS in SLE patients with mucocutaneous manifestations can be predicted by a higher titer, whereas in SLE patients who have only a rash, the presence of anti-EA (D) IgM-Abs was a predictor of remission and LLDAS.

[Assessment tools for systemic lupus erythematosus]. / Assessment-Tools für den systemischen Lupus erythematodes.

A systematic assessment is critical for taking advantage of the current options for optimizing systemic lupus erythematosus (SLE) management. Without regular SLE activity measurements, treat to target and remission are empty words, and the EULAR recommendations therefore insist on these assessments. They rely on activity scores, such as SLEDAI, ECLAM and BILAG or more recently, EasyBILAG and SLE-DAS. Assessment is completed by organ-specific measurement methods and the evaluation of damage. In the study setting the classification criteria and combined endpoints for clinical testing are crucial, as is measurement of the quality of life. This review article provides an overview of the current state of SLE assessments.

Real-world efficacy of belimumab in achieving remission or low-disease activity in systemic lupus erythematosus: A retrospective study.

OBJECTIVES: We investigated the effect of belimumab (BEL) on achieving low disease activity (LDA) and remission as an additive molecular-targeting agent to standard of care (SoC) in patients with SLE. METHODS: Clinical information was retrospectively collected from patients with SLE who received BEL additive to SoC (BEL+SoC), and from patients treated with SoC alone as a control arm. Disease activity was measured by SLE-disease activity score (SLE-DAS). The proportion of patients in LDA and remission at 12 months was compared after propensity score matching. The factors contributing to LDA and remission achievement was identified by Cox proportional hazard model. RESULTS: BEL+SoC significantly reduced SLE-DAS at 6 months, with a significantly higher proportion of patients achieving LDA and remission at 12 months compared to SoC alone. The presence of arthritis at baseline was significantly associated with achieving LDA and remission. Additionally, both treatment groups experienced a significant reduction in daily glucocorticoid dose. CONCLUSIONS: Adding BEL to SoC was beneficial for patients with arthritis, leading to higher proportion of achieving LDA and remission, while also reducing their glucocorticoid dose. Our results indicate the utility of BEL in a treat-to-target approach for SLE patients in a real-world setting.

Lupus Nephritis in Children: Novel Perspectives.

Childhood-onset systemic lupus erythematosus is an inflammatory and autoimmune condition characterized by heterogeneous multisystem involvement and a chronic course with unpredictable flares. Kidney involvement, commonly called lupus nephritis, mainly presents with immune complex-mediated glomerulonephritis and is more frequent and severe in adults. Despite a considerable improvement in long-term renal prognosis, children and adolescents with lupus nephritis still experience significant morbidity and mortality. Moreover, current literature often lacks pediatric-specific data, leading clinicians to rely exclusively on adult therapeutic approaches. This review aims to describe pediatric lupus nephritis and provide an overview of the novel perspectives on the pathogenetic mechanisms, histopathological classification, therapeutic approach, novel biomarkers, and follow-up targets in children and adolescents with lupus nephritis.

Peripheral immunophenotypes associated with the flare in the systemic lupus erythematosus patients with low disease activity state.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by clinical heterogeneity and flare unpredictability. It was still unclear for the association between SLE flare and immunophenotypes. Flow cytometric analysis defined the B and T subsets of the low disease activity state (LDAS) patients and healthy controls. Principal components analysis (PCA) and cluster analysis (CA) distinguished the immunophenotypes. Compared with the 66 healthy controls, the 93 LDAS patients had higher proportions of plasma cells, double negative B cells, naïve B cells and CD8+T cells, and lower proportions of unswitched memory B cells and CD4+T cells. PCA showed the abnormalities of T and B cell axes. CA divided the patients into 3 groups. The memory B cells group had the lower flare risk compared with the non-memory B cells group (including naïve B cells group and T cells group). The immunophenotypes were associated with SLE flare in the LDAS patients.

Lupus low disease activity state within 12 months is associated with favourable outcomes in severely active systemic lupus erythematosus.

OBJECTIVES: To demonstrate the significance of the time to attain lupus low disease activity state (LLDAS) after remission induction therapy in patients with severely active SLE. METHODS: We enrolled 79 patients starting prednisolone ≥0.4 mg/kg/day for active lupus with a BILAG 2004 index of A ≥ 1 or B ≥ 2, or for severe flare based on the Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI). The time to LLDAS attainment was divided into ≤6, 6-12 and >12 months and non-LLDAS; associations between the timing of LLDAS and flares, damage accrual and ≥50% LLDAS attainment were examined. RESULTS: The mean SLEDAI was 17; median starting dose of prednisolone, 0.95 mg/kg/day; and mean observational period, 39.7 months. Six (7.6%) and 41 (51.9%) patients achieved LLDAS within 6 and 12 months. Patients with a shorter time to LLDAS achievement were more likely to spend ≥50% of the time in LLDAS and had a lower cumulative prednisolone dose; no differences were observed in damage accrual. Patients requiring longer than 12 months to achieve LLDAS had a higher prevalence of thrombocytopenia and those with non-LLDAS had lower renal function and a higher starting dose of prednisolone and steroid pulse therapy than those who achieved LLDAS within 12 months. CONCLUSION: Achieving LLDAS within 12 months of induction therapy may be favourable in patients with severely active SLE. The low frequency of LLDAS attainment in high-risk populations highlights the need for a new strategy for SLE treatment.