Lupus Low Disease Activity State Research Articles

Association of systemic lupus erythematosus standard of care immunosuppressants with glucocorticoid use and disease outcomes: a multicentre cohort study

BackgroundThis study examines the association of standard-of-care systemic lupus erythematosus (SLE) medications with key outcomes such as low disease activity attainment, flares, damage accrual, and steroid-sparing, for which there is current paucity of data.MethodsThe Asia Pacific Lupus Collaboration (APLC) prospectively collects data across numerous sites regarding demographic and disease characteristics, medication use, and lupus outcomes. Using propensity score methods and panel logistic regression models, we determined the association between lupus medications and outcomes.ResultsAmong 1707 patients followed over 12,689 visits for a median of 2.19 years, 1332 (78.03%) patients achieved the Lupus Low Disease Activity State (LLDAS), 976 (57.18%) experienced flares, and on most visits patients were taking an anti-malarial (69.86%) or immunosuppressive drug (76.37%). Prednisolone, hydroxychloroquine and azathioprine were utilised with similar frequency across all organ domains; methotrexate for musculoskeletal activity. There were differences in medication utilisation between countries, with hydroxychloroquine less frequently, and calcineurin inhibitors more frequently, used in Japan. More patients taking leflunomide, methotrexate, chloroquine/hydroxychloroquine, azathioprine, and mycophenolate mofetil/mycophenolic acid were taking ≤ 7.5 mg/day of prednisolone (compared to > 7.5 mg/day) suggesting a steroid-sparing effect. Patients taking tacrolimus were more likely (Odds Ratio [95% Confidence Interval] 13.58 [2.23–82.78], p = 0.005) to attain LLDAS. Patients taking azathioprine (OR 0.67 [0.53–0.86], p = 0.001) and methotrexate (OR 0.68 [0.47–0.98], p = 0.038) were less likely to attain LLDAS. Patients taking mycophenolate mofetil were less likely to experience a flare (OR 0.79 [0.64–0.97], p = 0.025). None of the drugs was associated with a reduction in damage accrual.ConclusionsThis study suggests a steroid-sparing benefit for most commonly used standard of care immunosuppressants used in SLE treatment, some of which were associated with an increased likelihood of attaining LLDAS, or reduced incidence of flares. It also highlights the unmet need for effective treatments in lupus.

TNFSF13B rs9514828 C>T Polymorphism is Associated with Incidence of Atherosclerosis and Therapeutic Outcomes in Patients with Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with numerous clinical manifestations. Organ involvement can aggravate patients with SLE and cause comorbidities such as atherosclerosis. Recently, the TNFSF13B gene has been found to be linked with SLE events. This study aimed to analyze the association between single nucleotide polymorphisms of the TNFSF13B rs9514828 with incidence of atherosclerosis and therapeutic outcomes in patients with SLE. This case-control study included 84 SLE patients, of whom 21 patients with SLE with atherosclerosis and 63 patients with SLE without atherosclerosis. Using enzyme-linked immunosorbent assay method, interleukin-6 and interferon gamma levels were quantified. The TNFSF13B gene polymorphism was evaluated using polymerase chain reaction followed by sequencing. The lupus low disease activity state (LLDAS) criteria were used to measure the therapeutic outcomes. Statistical analysis was conducted using binary logistic regression. The genetic variations of TNFSF13B rs9514828 were CC = 35, CT = 41, and TT = 8. There was an association between TNFSF13B rs9514828 C>T polymorphism in patients with SLE with and without atherosclerosis (p = 0.03; odds ratio (OR) 4.72, 95% confidence interval [CI] 1.22-18.37). Furthermore, the TNFSF13B rs9514828 C>T polymorphism had association with the therapeutic outcomes of patients with SLE who manifested with LLDAS (p = 0.00; OR 7.58, 95% CI 2.61-21.99). The association of TNFSF13B rs9514828 C>T polymorphism and incidence of atherosclerosis as well as the therapeutic outcomes in patients with SLE indicate the potential utility of the gene variation as screening tool to employ personalized medicine to undertake preventive measures in order to prevent atherosclerosis and to predict a poor prognosis in SLE patient.

Efficacy and safety of the type I interferon receptor inhibitor anifrolumab in patients with systemic lupus erythematosus (results of a 6-month study)

Objective: to evaluate the efficacy and safety of the type I interferon (IFN) receptor inhibitor anifrolumab (AFM, Safnelo®) in patients with systemic lupus erythematosus (SLE) in real-life clinical practice over an observation period of 6 months.Material and methods. The prospective 6-month study included 21 patients with SLE fulfilling the 2012 SLICC criteria, predominantly women (n=17,81%), median age – 31 [27; 46] years, disease duration – 9 [6.0; 11.0] years. Standard laboratory values and immunological markers of SLE were examined in all patients. The SLEDAI-2K index was used to determine the activity of SLE, and the severity of the mucocutaneous syndrome was assessed using the Cutaneous Lupus Disease Area and Severity Index (CLASI) index. Organ damage was assessed using the SLICC/ACR Damage Index (DI). After 6 months, the achievement of low activity was assessed according to the Lupus Low Disease Activity State (LLDAS) indexResults and discussion. At the time of inclusion in the study, the mean SLEDAI-2K activity index for the group was 8 [6.0; 10.0] points, the median CLASI index – 8.6±8.2 points, 81% of patients had skin and mucosal lesions, 66% had non-erosive polyarthritis, and high immunological activity was observed in all cases. Various irreversible organ damage was observed in 86 of patients. The average DI was 2.2±1.5 points. At the start of AFM therapy, all patients received glucocorticoids (GCs) at a mean dose of 10.7±5.6 mg/day, 52% of patients received a dose above 10 mg/day, 76% of patients continued to take hydroxychloroquine, and 33% of patients took immunosuppressants. Significant positive dynamics were observed with AFM therapy. The average CLASI index for the group after 3 months of treatment was 1.2±4.1 points, after 6 months – 0.3±1.2 points (p<0.0001). The SLEDAI-2K index fell significantly in the group on average from 8 [6.0; 10.0] to 2 [2.0; 4.0] points from the 3rd month of treatment (p<0.0001) and remained at the same level after 6 months. At month 6 of treatment, 13 (62%) of 21 patients met the LLDAS criteria for low disease activity. After the 3rd month of treatment, a significant decrease in antibodies against dsDNA was observed, which persisted for 6 months after the start of treatment. In the group as a whole, there were no significant changes in complement fractions values during the observation period. There was no increase in irreversible organ damage (DI – mean 2.2±1.5 points). The mean daily dose of GCs was significantly reduced from 10.7±5.6 mg/day to 7.5±4.0 mg/day (p<0.01) by the 3rd month and to 5.2±2.1 (p<0.001) by the 6th month of treatment. No infusion reactions were observed in any case. Adverse events occurred in 9 (42%) out of 21 patients, mainly herpes infections of varying severity, mainly after the 1st to 3rd infusions. In one case, severe herpes zoster was observed, so the drug was discontinued.Conclusion. At a dose of 300 mg intravenously monthly AFM is a highly effective drug with a relatively good safety profile in patients with active SLE in whom autoantibodies are present and who do not respond adequately to standard therapy.

Analysis of belimumab prescription and outcomes in a 10-year monocentric cohort: is there an advantage with early use?

ObjectiveThe objective is to evaluate perscriptions of belimumab (BEL), how these have changed over the years and their impact on clinical outcomes in patients with systemic lupus erythematosus (SLE).MethodsThis is...

Baixo estado de atividade da doença e avaliação de dano permanente em pacientes ambulatoriais com lúpus eritematoso sistêmico

ObjectiveVerify the association between low disease activity and damage accrual in Systemic Lupus Erythematosus patients.MethodsWe evaluated 60 patients following the Rheumatology Out patient Clinic with American College of Rheumatology and European League Against Rheumatism of Systemic Lupus Erythematosus diagnostic criteria. We evaluated clinical and demographic data like gender, age, and disease duration. We evaluated disease activity using the Systemic Lupus Erythematosus Low disease activity score, and damage accrual we evaluated using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index for systemic lupus erythematosus. The Chi-Square test realized statistical analysis, and a level of 0.05 was considered significant.ResultsOn 60 patients studied, we found lupus low disease activity state in 45 (75%) and 15 (25%) were in disease activity. Concerning damage accrual, we found that 11 (42.3%) had damage, and 40 (66,6%) did not have damage. Five patients with damage did not have disease activity, and 40 with no activity did not have damage. Of patients with disease activity, 11 we found with damage, and no damage was found in nine. Females predominate in this population with 98.3% of patients; the mean age was 43.4 years old, and the mean disease duration was 12.8 years. The statistical analysis results showed an association between low disease activity and no damage accrual in SLE patients (p<0.005).ConclusionOur results demonstrated an association between low disease activity and no damage accrual in systemic lupus erythematosus patients.

Comparison of Attainment and Protective Effects of Lupus Low Disease Activity State In Patients With Newly Diagnosed Versus Established Systemic Lupus Erythematosus.

To assess whether Lupus Low Disease Activity State (LLDAS) attainment is associated with favorable outcomes in patients with recent onset systemic lupus erythematosus (SLE). Data from a 13-country longitudinal SLE cohort were collected prospectively between 2013 and 2020. An inception cohort was defined based on disease duration < 1 year at enrollment. Patient characteristics between inception and noninception cohorts were compared. Survival analyses were performed to examine the association between LLDAS attainment and damage accrual and flare. Of the total 4106 patients, 680 (16.6%) were recruited within 1 year of SLE diagnosis (inception cohort). Compared to the noninception cohort, inception cohort patients were significantly younger, had higher disease activity, and used more glucocorticoids, but had less organ damage at enrollment. Significantly fewer inception cohort patients were in LLDAS at enrollment than the noninception cohort (29.6% vs 52.3%, P < 0.001), but three-quarters of both groups achieved LLDAS at least once during follow-up. Limiting analysis only to patients not in LLDAS at enrollment, inception cohort patients were 60% more likely to attain LLDAS (hazard ratio 1.37, 95% CI 1.16-1.61, P < 0.001) than noninception cohort patients and attained LLDAS significantly faster. LLDAS attainment was significantly protective against flare in both the inception and noninception cohorts. A total of 88 (13.6%) inception cohort patients accrued organ damage during a median 2.2 years of follow-up. LLDAS attainment is protective from flare in recent onset SLE. Significant protection from damage accrual was not observed because of low rates of damage accrual in the first years after SLE diagnosis. (ClinicalTrials.gov: NCT03138941).

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

ObjectivesTo 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. MethodsProspective 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. ResultsFifty 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. ConclusionTime 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.

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.

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. 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. 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. 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.

Molecular characterisation of lupus low disease activity state (LLDAS) and DORIS remission by whole-blood transcriptome-based pathways in a pan-European systemic lupus erythematosus cohort

ObjectivesTo unveil biological milieus underlying low disease activity (LDA) and remission versus active systemic lupus erythematosus (SLE).MethodsWe determined differentially expressed pathways (DEPs) in SLE patients from the PRECISESADS project (NTC02890121)...

Histone-Specific CD4+ T Cell Plasticity in Active and Quiescent Systemic Lupus Erythematosus.

The aim of this study was to assess whether circulating histone-specific T cells represent tools for precision medicine in systemic lupus erythematosus (SLE). Seroprevalence of autoantibodies and HLA-DR beta (DRB) 1 profile were assessed among 185 patients with SLE and combined with bioinformatics and literature evidence to identify HLA-peptide autoepitope couples for ex vivo detection of antigen-specific T cells through flow cytometry. T cell differentiation and polarization was investigated in patients with SLE, patients with Takayasu arteritis, and healthy controls carrying HLA-DRB1*03:01 and/or HLA-DRB1*11:01. SLE Disease Activity Index 2000 and Lupus Low Disease Activity State were used to estimate disease activity and remission. Histone-specific CD4+ T cells were selectively detected in patients with SLE. Among patients with a history of anti-DNA antibodies, 77% had detectable histone-specific T cells, whereas 50% had lymphocytes releasing cytokines or upregulating activation markers after in vitro challenge with histone peptide antigens. Histone-specific regulatory and effector T helper (Th) 1-, Th2-, and atypical Th1/Th17 (Th1*)-polarized cells were significantly more abundant in patients with SLE with quiescent disease. In contrast, total Th1-, Th2-, and Th1*-polarized and regulatory T cells were similarly represented between patients and controls or patients with SLE with active versus quiescent disease. Histone-specific effector memory T cells accumulated in the blood of patients with quiescent SLE, whereas total effector memory T cell counts did not change. Immunosuppressants were associated with expanded CD4+ histone-specific naive T (TN ) and terminally differentiated T cells. Histone-specific T cells are selectively detected in patients with SLE, and their concentration in the blood varies with disease activity, suggesting that they represent innovative tools for patient stratification and therapy.

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...

CD19/BCMA CAR-T Cell Therapy for Refractory Systemic Lupus Erythematosus - Safety and Preliminary Efficacy Data from a Phase I Clinical Study

Background: Despite significant advances in the treatment of systemic lupus erythematosus (SLE), a subset of patients continue to experience severe progression of their disease despite multiple immunosuppressive and targeted therapies. Furthermore, to date, drug-free remission and seroconversion have been difficult to achieve in SLE. CD19 single-targeted chimeric antigen receptor (CAR) T-cell therapies have shown promising efficacy in SLE but have been unable to attack CD19-negative, long-lived plasma cells, which produce numerous antibodies.This trial aims to study the safety, tolerability and preliminary efficacy of deep B-cell clearance in patients with refractory SLE using autologous anti-CD19 and BCMA CAR-T cells. Method: The CAR product was manufactured by Shanghai YaKe Biotechnology Ltd. The clinical study was conducted in a dose-escalation format. T cells were enriched from patient's peripheral blood, transfected with lentiviral vectors and expanded. After lymphodepleting chemotherapy with cyclophosphamide/fludarabine (D-4 to D-2), patients receive a single infusion of 1-2x106 CD19 CAR-T cells and BCMA CAR-T cells per kilogram of body weight at D0. On the first day of chemotherapy initiation , all SLE-related immunosuppressants, biologics, etc. were discontinued except for a few patients who were maintained on low-dose prednisolone. Tolerability was assessed by monitoring cytokine release syndrome (CRS), immune-related effector cell neurotoxicity syndrome (ICANS), and infections. Initial efficacy was assessed by attainment of lupus low disease activity state (LLDAS), dsDNA antibody and ANA seroconversion, and discontinuation of all SLE-specific therapies. Results: As of July 31, 2023, 12 patients with refractory SLE were treated with CD19/BCMA CAR-T cells with a median follow-up of 118.5 (45-524) days. All patients had active severe SLE and had received glucocorticoids, hydroxychloroquine, tacrolimus, total glucosides of paeony, merti-macrolide, leflunomide, azathioprine, methotrexate, cyclophosphamide, immunoglobulin, rituximab, belimumab, and Tetracycline before treatment with CAR-T cells, which were standard treatments that were either ineffective or difficult to withdraw.3 patients received 1x10^6/kg of each of CD19 CAR-T cells and BCMA CAR-T cells, and 9 patients received 2x10^6/kg of each of CD19 CAR-T cells and BCMA CAR-T cells 2x10^6/kg. CAR-T cells were prepared successfully in all patients. BCMA CAR-T achieved expansion in all patients, while CD19 CAR-T did not expand in 1 patient, and expansion of CAR T cells preceded depletion of circulating B cells. All patients developed grade 1 CRS, which manifested as controllable fever, and no ICANS occurred. 11 patients (91.7%) developed grade 4 hematologic toxicity, and 1 patient (8.3%) developed grade 3 hematologic toxicity. Within 6 months of CAR-T treatment, 2 patients were infected with neocoronavirus, 1 patient developed gastrointestinal tract infection, and 1 patient developed pulmonary infection , and all of them recovered after treatment. The SLEDAI-2K score decreased in all patients, from a mean of 18.3 to 1.5. Low-level proteinuria persisted in some patients, possibly due to previously accumulated glomerular filtration impairment. All patients met LLDAS criteria and were able to successfully discontinue all SLE-related medications, including glucocorticoids. peripheral blood B cells recovered at approximately 3 months after CAR-T therapy. To date, no SLE flares have occurred. Conclusions: These data suggest that CD19/BCMA CAR-T cell therapy is well tolerated and can induce rapid and durable remission in severe refractory SLE.

Efficacy and safety of telitacicept in patients with systemic lupus erythematosus: a multicentre, retrospective, real-world study

ObjectiveTo examine the efficacy and safety of telitacicept in the treatment of patients with SLE in everyday clinical practice.MethodsSeventy-two patients with active SLE who received telitacicept for more than 24...

Efficacy of baricitinib for the treatment of systemic lupus erythematosus patients: A meta-analysis of randomized controlled trials.

Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by abnormal autoantibody production, inflammation, and organ damage. Most SLE treatment strategies aim to induce remission or reduce disease activity while avoiding flares. Baricitinib has been used effectively to manage various inflammatory diseases, and some randomized controlled trials (RCT) have shown that it is beneficial in treating SLE. The current study aims to assess the efficacy of baricitinib in treating SLE patients. Various databases such as PubMed, Scopus, and Science Direct were searched to obtain eligible studies for the present meta-analysis. Data such as baseline characteristics of patients, doses of the baricitinib, follow-up duration, and treatment outcome in the form of SLE responder index-4 (SRI-4) and lupus low disease activity state (LLDAS) were extracted. Combined odds ratio, 95% confidence interval, and probability values were calculated to study the efficacy of baricitinib in treating SLE patients. A p-value less than .05 was taken as significant. Comprehensive meta-analysis v3 was used for all analyses. Three articles were found eligible for the present meta-analysis comprising 614 patients with placebo, 614 SLE patients receiving 4 mg, and 621 patients with 2 mg of baricitinib. Meta-analysis revealed a beneficial effect of 4 mg baricitinib in SLE patients compared to placebo, as measured by an increase in the SRI-4 (p = .006, OR = 1.370) and LLDAS (p = .083, OR = 1.252) rates. In contrast to the placebo group, however, patients receiving 2 mg of baricitinib exhibited no significant improvement. The trial sequential analysis revealed the need for additional RCTs to determine the role of baricitinib in treating SLE patients. In treating SLE patients, administrating a higher dose of baricitinib (4 mg) may be effective. However, additional RCTs in different populations with larger sample sizes are required to validate our findings.

Safety and efficacy of anifrolumab therapy in systemic lupus erythematosus in real-world clinical practice: LOOPS registry

Abstract Objective To determine the safety and efficacy of anifrolumab in patients with systemic lupus erythematosus (SLE) classified based on the Lupus Low Disease Activity State (LLDAS) in real-world clinical practice. Methods This retrospective observational study involved SLE patients who started anifrolumab therapy. The primary end point was the retention rate over 26 weeks after initiating anifrolumab therapy; 45 patients followed up for 12 weeks or longer were analysed in the following groups to determine the safety and efficacy up to week 12 after treatment initiation: (i) non-LLDAS achievement group and (ii) minor flare group. Safety and efficacy were compared between the minor flare group and the standard of care (SoC) group (treated by adding glucocorticoids [GCs] or immunosuppressants) after adjustment with inverse probability of treatment weighting using propensity score (PS-IPTW). Results The retention rate of anifrolumab was 89.7% at week 26.The LLDAS achievement rates at week 12 were 42.9% and 66.7% in the non-LLDAS achievement and minor flare groups, respectively. In both groups, GC doses and SELENA–SLEDAI score significantly decreased. When the anifrolumab group with minor flare was compared with the SoC group or the GC dose increase group, the GC dose and SLEDAI score were significantly lower in the anifrolumab group than in either of the other groups; there was no significant difference in LLDAS achievement. Conclusion At week 26 after initiating anifrolumab therapy, ∼90% of patients remained on therapy. Anifrolumab might lower disease activity without initiating GCs and reduce GC doses, especially in patients who experience minor flares after LLDAS achievement.

Abstract 15 — Lupus Low Disease Activity State: An Underutilised Clinical Target that is Attainable and Protective against Lupus Nephritis Relapse

Background Lupus nephritis (LN) is a significant comorbidity affecting approximately 50-60% of patients with systemic lupus erythematosus (SLE). Complete and partial renal response (CRR/PRR) have been recommended as treatment targets in LN. Lupus low disease activity state (LLDAS) is also associated with favourable clinical outcomes. This study aims to investigate the LLDAS attainment rate and outcomes in patients with LN. Methods Patients with biopsy-proven LN during 2010-2020 in Queen Mary Hospital were included. Baseline demographics, blood parameters and urinalysis results were documented. Renal response and LLDAS attainment were assessed at 12 months after LN diagnosis. CRR was defined as proteinuria [Formula: see text]0.5g/day with a normal estimated glomerular filtration rate (eGFR); PRR was defined as a reduction in proteinuria by [Formula: see text]50% with near normal eGFR. A relapse was defined as a biopsy-proven active LN on histology after an initial treatment response of proteinuria reduction of [Formula: see text]50% or to sub-nephrotic range. Time-to-relapse survival analysis was performed to compare the significance of CRR/PRR and LLDAS attainment. Results 143 LN patients were included, with a median follow-up duration of 10.4 years. At 12 months, 57 (40%), 14 (10%) and 69 (48%) patients achieved CRR, PRR and LLDAS, respectively. Although 39 (27%) patients attained both CRR/PRR and LLDAS, a significant number of 30 (21%) patients reached LLDAS without meeting CRR/PRR (Figure 1). Among 136 patients who achieved the pre-defined treatment response, 30 (22%) patients developed LN relapse after a median of 2.98 years. Patients reaching either CRR/PRR or LLDAS had a significantly lower risk of relapse (CRR/PRR: HR = 0.34, p = 0.02; LLDAS: HR = 0.28, p = 0.003). The attainment of both CRR/PRR and LLDAS was associated with the lowest risk of relapse (Figure 2). Conclusion We advocate LLDAS as a target for LN patients as attaining LLDAS reduces future LN relapse risks.

The correlation between pregnancy, disease activity and adverse pregnancy outcomes in patients with systemic lupus erythematosus.

In this study, our pregnant systemic lupus erythematosus (SLE) cohort, which was under medical surveillance of both our Rheumatology and Obstetrics departments, was analyzed. We intended to determine the effects of pregnancy on disease activity and the correlation between disease flares and adverse pregnancy outcomes. One hundred sixty eight pregnancy data involving 136 patients with SLE were examined. Cumulative clinical, laboratory, and serological parameters were described. Disease activity and flares were calculated using the systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K) in the pre/postpartum periods and the SLEPDAI in the three trimesters of pregnancy. Patients with a SLEDAI-2K or SLEPDAI ≥ 4 were classified as "active." Patients with lupus low disease activity state (LLDAS) during each of these periods were identified.Fetal/neonatal death, premature birth due to pre-eclampsia, eclampsia or hemolysis, elevated Liver enzymes (HELLP) syndrome, and neonates small for gestational age were determined as adverse pregnancy outcomes (APO). Out of 168 pregnancies, there were 60 (35.7%) pregnancies with flares covering the pregnancy and 6months of postpartum period. The mean SLEDAI in the 6months postpartum period was significantly higher compared to mean disease activity during pregnancy (p < .05). Of all pregnancies, 132 (78.6%) were in LLDAS during pregnancy. Comparison of the frequency of severe postpartum flares in patients who were in LLDAS during pregnancy revealed a lower percentage of flares compared to those who were not in the LLDAS group (11 vs 29%, p < .05). APO was observed in 33.9% of 168 pregnancies. The mean SLEPDAI score was significantly higher in APO+ pregnancies than in APO- pregnancies (4.9 ± 6.1 vs 2.8 ± 4.9, p = .002). Comparison of SLICC damage score between APO - and + pregnancies revealed a significantly higher score in APO+ pregnancies (1.8 ± 2.1 vs 0.8 ± 1.3, p = .001). Postpartum six-month period appears to have the highest risk for disease flares during SLE pregnancies. Disease activity during pregnancy increases the risk of APO. In order to achieve a positive pregnancy outcome and lower maternal morbidity, regular follow-up of patients is necessary.

Disease-modifying effect and long-term safety of belimumab in patients with systemic lupus erythematosus: A single-center retrospective study.

Disease modification in systemic lupus erythematosus (SLE) is important for minimizing disease activity while limiting treatment-associated toxicities. Belimumab can be used as a remission-induction/maintenance systemic lupus erythematosus therapy; however, its disease-modifying effects are unclear. We aimed to determine these effects in patients with systemic lupus erythematosus. This single-center retrospective cohort study included 92 patients with systemic lupus erythematosus treated with belimumab. We analyzed the changes in flare free rate/lupus low disease activity state (LLDAS) attainment rate/glucocorticoid dosage/Systemic Lupus International Collaborating Clinics and American College of Rheumatology damage index (SDI) score/drug retention rate after treatment initiation. Fifty-two weeks after initiating belimumab, the flare rate decreased from 82.6% to 14.1% (p < .01). Until week 52 and 1000days after initiating belimumab treatment, > 70% and ∼90% of the patients attained lupus low disease activity state, respectively. Belimumab treatment significantly reduced glucocorticoid demand (initiation day, 8.88 (6.00-15.00) mg/d; week 52, 5.00 (2.00-7.00) mg/d; final day of the study period, 3.00 (0.46-6.06) mg/d, initiation day vs. week 52: p < .01, initiation day vs. final day: p < .01); at the end of the study period, 68.5% of patients required ≤5mg/d prednisolone, and 22.8% discontinued glucocorticoids. Most patients were SDI progression-free (week 52, ∼95%; day 1000, ∼90%), and belimumab showed a high drug retention rate (week 52, 90%; day 1000 > 80%). Most patients experienced lupus low disease activity state, reduced flare rate and glucocorticoid demand, and a stable SDI trend after belimumab treatment initiation. Given its efficacy and retention rate, belimumab treatment may serve as a fundamental strategy in disease modification.

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.