OBJECTIVE: This study aimed to evaluate the clinical efficacy of belimumab in patients with early systemic lupus erythematosus (SLE), defined as having a disease duration of less than 6 months.
METHODS: We retrospectively identified patients with SLE in the early stage who received belimumab and standard of care (belimumab group) or standard of care alone (control group) since September 2020. Propensity score matching (PSM) was used to reduce potential bias. The primary endpoint was lupus low disease activity status (LLDAS) at weeks 12 and 24. The secondary endpoints were remission and the proportion of glucocorticoid dose tapering to 7.5 mg/day. The efficacy of belimumab in patients with lupus nephritis was also assessed.
RESULTS: Out of 111 eligible patients, 16 patients in the belimumab group and 31 patients in the control group were identified by 1:2 PSM. At week 24, a significantly higher proportion of individuals achieved low disease activity state (LLDAS) in the belimumab group compared to the control group (56.3% vs. 19.4%, OR = 5.357, 95% CI = 1.417 to 20.260, p = 0.013). Furthermore, more patients in the belimumab group were reduced to low-dose glucocorticoid ( ≤ 7.5 mg/day) at week 24 (75.0% vs. 35.5%, OR = 5.182, 95%CI = 1.339 to 20.058, p = 0.017). Significant improvements in Patient Global Assessment scores were observed at Week 12 and 24 for those treated with belimumab compared to controls. In a subgroup analysis evaluating the efficacy of belimumab in patients with lupus nephritis, 42.9% of the seven individuals treated with belimumab achieved a complete renal response (CRR) by Week 24, and no instances of disease relapse were observed.
CONCLUSIONS: In SLE patients with a disease duration of less than 6 months, belimumab treatment can promote LLDAS achievement and reduce glucocorticoid dose, leading to a better prognosis. Introducing belimumab in the early stage of SLE may be a beneficial decision.

OBJECTIVE: The aims of this study were to investigate the prevalence of dose reduction in patients with SLE treated with belimumab (BEL) in Spain, analyze treatment modalities, and determine impact on control of disease activity.
METHODS: Retrospective longitudinal and multicentre study of SLE patients treated with BEL. Data on disease activity, treatments and outcomes were recorded before and after reduction (6-12 months), and they were compared.
RESULTS: A total of 324 patients were included. The dose was reduced in 29 patients (8.9%). The dosing interval was increased in 9 patients receiving subcutaneous BEL and in 6 patients receiving intravenous BEL. The dose per administration was reduced in 16 patients.Pre-reduction status was remission (2021 DORIS) in 15/26 patients (57.7%) and LLDAS in 23/26 patients (88.5%). After reduction, 2/24 patients (8.3%) and 3/22 patients (13.6%) lost remission at 6 months and 12 months, respectively (not statistically significant [NS]). As for LLDAS, 2/23 patients (8.7%) and 2/21 patients (9.5%) lost their status at 6 and 12 months, respectively (NS). Significantly fewer patients were taking glucocorticoids (GCs) at their 12-month visit, although the median dose of GCs was higher at the 12-month visit (5 [0.62-8.75] vs 2.5 [0-5] at baseline).
CONCLUSIONS: Doses of BEL can be reduced with no relevant changes in disease activity-at least in the short term-in a significant percentage of patients, and most maintain the reduced dose. However, increased clinical or serologic activity may be observed in some patients. Consequently, tighter post-reduction follow-up is advisable.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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.

OBJECTIVE: To provide an overview on the current use of belimumab (BLM) in SLE patients in clinical practice and to examine its efficacy in terms of standardized outcomes, drug survival, as well as patient and safety profiles.
METHODS: A longitudinal retrospective multicentre cohort including SLE patients treated with BLM at 18 Spanish centers. Data was collected upon initiation of BLM, at 6 and 12 months after initiation, and at the last recorded visit. Changes in SLEDAI-2K, the proportion of patients who achieved LLDAS and DORIS 2021, and number of flares were compared between visits. Changes in damage, glucocorticoids use and employment status pre-BLM and post-BLM were also assessed.
RESULTS: A total of 324 patients were included with a mean follow-up of 3.8 (±2.7) years. LLDAS was attained by 45.8%, 62% and 71% of patients, and DORIS by 24%, 36.2% and 52.5% on successive visits, respectively. Twenty-seven-point two percent of patients were in DORIS ≥ 50% of the visits and a 46% in LLDAS-50. Flares and number of flares were significantly lower one year after treatment with BLM and no changes in damage accrual were observed. Mean (±SD) prednisone dose was significantly reduced over time, with 70 (24%) patients discontinuing GC.
CONCLUSIONS: Our study not only demonstrates belimumab´s efficacy in attaining treat-to-target goals in SLE patients, but also confirms its GC-sparing effect, and its prevention of flares and organ damage accrual.

Systemic Lupus Erythematosus is a systemic autoimmune disease characterized by a great heterogenicity in course and clinical manifestations. Although prognosis improved in the last decades of the 20th century, mortality remains higher than in the general population and uncontrolled disease activity and therapy-related adverse effects have been identified as major contributors to damage accrual and poor outcomes. Assessment of disease activity and damage in SLE represents a great challenge even to the expert rheumatologist. Global disease activity indices are tools developed to assess activity across multiple organ systems. Several disease activity indices have been developed over the years, each with its own strengths and weaknesses, and knowing them is essential for understanding research studies, such as clinical trials, in which they are used. Organ-specific activity indices have been developed concurrently to represent organ involvement such as glomerulonephritis, cutaneous and musculoskeletal lupus manifestations. Regarding damage, the SLICC/ACR damage index has proven to be an effective tool for damage accrual assessment, yet not devoid of drawbacks. This review provides an overview of the most frequently utilized indices developed for the assessment of activity and damage in SLE highlighting their pros and cons when applied to the research and clinical setting.

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.
Systemic lupus erythematosus (SLE) is a complex disease that can affect many organs. It can lead to life-threatening complications and poor quality of life. As SLE is very different in each person, it can be challenging to measure disease activity. Doctors are encouraged to set clinical targets to tailor treatment for each patient. Clinical targets include scoring systems that measure disease improvement. Remission is an established clinical target. When a patient is in remission, disease activity is controlled, and the patient does not experience any symptoms. As remission is difficult to achieve, experts developed a more realistic yet still favorable state. This is the lupus low disease activity state, when lupus symptoms are minimal on stable therapy. Doctors use remission and low disease activity in clinical trials to compare existing SLE drugs with new treatments, including biologic drugs. Biologics target key parts of the immune system to help suppress SLE. In this review, we looked at recent clinical trials and found that biologic drugs can help patients achieve remission or low disease activity. Patients who achieved these clinical targets had slower disease progression and improved quality of life. Clinical trials in SLE should continue to use remission and low disease activity targets to help compare treatments. Doctors are encouraged to use them in their routine clinics as treatment targets to measure SLE disease control. Low disease activity state may be particularly helpful as an initial target for patients who are not yet in remission.

Glucocorticoids (GCs) remain a cornerstone of the treatment of Systemic Lupus Erythematosus (SLE). Numerous studies have emphasized the risk of damage accrual in SLE patient treated with GC, but currently, it is not possible to dissociate favorable and undesirable effects of GCs because their underlying mechanisms are entangled at the molecular level. Here, we review whether available data suggest that it is possible, feasible and desirable to taper and discontinue GC treatment in SLE. The main potential concern with GC withdrawal is the risk of SLE flare, which is strongly associated with increased organ damage, mortality, healthcare costs, decreased quality of life and work productivity. While most studies have assumed the cut off point for low doses (e.g. 7.5/mg/d) as the limit for safety, it is still controversial whether lower doses may influence damage accrual long-term. Also, a recent randomized trial has shown that a daily dose of 5 mg of prednisone in SLE patients in short-term remission can prevent up to 50-75% of flares, with an acceptable safety profile. However, this treatment is not mandatory for all patients. Yet, several observational studies highlight that discontinuation of GC is associated with lower damage accrual. Currently, we do not have a reliable method to identify patients who may require long-term low-dose GC. Therefore, further research is needed to identify a subgroup at high risk of relapse who would benefit from continuing prednisone. In the meantime, when considering the discontinuation of very low-dose prednisone, the decision must be individualized, as HCQ and conventional immunosuppressive agents are not without risk of side effects.

BACKGROUND: At present, the treat-to-target approach has been proposed with the lupus low disease activity state (LLDAS) as an achievable target.
OBJECTIVE: To determine damage accrual and baseline clinical characteristics associated with achieving LLDAS within 12 months of treatment in patients with childhood-onset systemic lupus erythematosus (c-SLE).
METHODS: This retrospective cohort study was conducted at the largest university-based tertiary referral center in Thailand. Data of c-SLE patients (≤ 18 years) at diagnosis who were followed ≥ 12 months during January 2009 to December 2019 were collected. SLE disease status was categorized into LLDAS and non-optimally controlled state. SLEDAI-2K score was used to assess disease activity. Damage accrual was assessed by a pediatric version of the SLICC/ACR damage index.
RESULTS: A total of 232 c-SLE patients (85.8% female) were included. At 12 months of treatment, 109 (47%) patients achieved LLDAS. Damage accrual was observed in 93 (40.1%) patients at the mean follow-up time of 6.2 ± 3.7 years. Damage accrual was significantly lower in patients who achieved LLDAS within 12 months than in those non-optimally controlled (p = 0.002). The median time to achieving LLDAS was 12.6 months (95%CI: 11.19-13.97). The median time to achieving LLDAS was significantly shorter in those without renal involvement (10.8 months, 95%CI: 9.62-12.00 vs. 15.6 months, 95%CI: 13.76-17.52, respectively; p = 0.044). Multivariable logistic regression analysis revealed absence of renal involvement as the predictor of achieving LLDAS within 12 months of treatment (aOR: 2.430, 95%CI: 1.420-4.158; p = 0.001).
CONCLUSIONS: Achieving LLDAS within 12 months of treatment was associated with lower damage accrual. Absence of renal involvement was the predictor of achieving LLDAS within 12 months of treatment. Key Points • LLDAS is a promising and achievable treatment target in c-SLE. • Achieving LLDAS within 12 months of treatment is associated with lower damage accrual. • Absence of renal involvement is the predictor of achieving LLDAS within 12 months of treatment.

To apply the lupus low disease activity state (LLDAS) definition within a large cohort of patients and to assess the agreement between the LLDAS and the physician\'s subjective evaluation of lupus activity.
We conducted a cross-sectional analysis of a prospective multicentre study of SLE patients. We applied the LLDAS and assessed whether there was agreement with the clinical status according to the physician\'s opinion.
A total of 508 patients [92% women; mean age 50.4 years (s.d. 3.7)] were recruited and 304 (62.7%) patients were in the LLDAS. According to physician assessment, 430 (86.1%) patients were classified as remission or low activity. Overall agreement between both evaluations was 71.4% (95% CI: 70.1, 70.5) with a Cohen\'s κ of 0.3 [interquartile range (IQR) 0.22-0.37]. Most cases (96.1%) in the LLDAS were classified as remission or low activity by the expert. Of the patients who did not fulfil the LLDAS, 126 (70.4%) were classified as having remission/low disease activity. The main reasons for these discrepancies were the presence of new manifestations compared with the previous visit and a SLEDAI 2K score >4, mainly based on serological activity.
Almost two-thirds of SLE patients were in the LLDAS. There was a fair correlation between the LLDAS and the physician\'s evaluation. This agreement improves for patients fulfilling the LLDAS criteria. The discordance between both at defining lupus low activity, the demonstrated association of the LLDAS with better outcomes and the fact that the LLDAS is more stringent than the physician\'s opinion imply that we should use the LLDAS as a treat-to-target goal.

OBJECTIVE: To derive and validate a definition of low disease activity (LDA) for systemic lupus erythematosus (SLE) based on the SLE Disease Activity Score (SLE-DAS), in a real-life multicentre cohort of SLE patients.
METHODS: Derivation was conducted using data from a monocentric cohort of SLE (Portugal), and validation was performed in a multicentre cohort (Italy, France, and Spain). The Lupus Low Disease Activity State (LLDAS) was used as comparator. We applied receiver operating characteristics (ROC) curve analysis against the LLDAS to determine the cut-off of SLE-DAS for LDA using bootstrap methodology. In a second step, we tested a definition of SLE-DAS LDA that included: (i) the statistically derived SLE-DAS upper threshold for LDA, and (ii) prednisone dose ≤7.5 mg/day. In the multicentre validation cohort, we assessed the classification performance of this SLE-DAS LDA definition.
RESULTS: We included 774 patients, 300 in the derivation and 474 in the validation cohorts, respectively. In the derivation cohort, the optimal cut-off to identify patients in LLDAS was SLE-DAS ≤2.48, presenting an area under the curve (AUC) of 0.965 (95%CI 0.935-0.994). When applied to the multicentre validation cohort, the SLE-DAS LDA definition showed a sensitivity of 97.1% and a specificity of 97.7% for LLDAS and an almost perfect agreement (Cohen\'s Kappa =0.933; p< 0.001). McNemar\'s test found no significant differences between the two definitions (p= 0.092).
CONCLUSIONS: The SLE-DAS LDA is a validated, accurate, and easy-to-use definition for classifying SLE patients in LDA state.