Lupus Nephritis Patients Research Articles

WCN25-1838 A STUDY ON TREATMENT OUTCOME OF LUPUS NEPHRITIS PATIENTS IN SOUTH INDIAN POPULATION

WCN25-1838 A STUDY ON TREATMENT OUTCOME OF LUPUS NEPHRITIS PATIENTS IN SOUTH INDIAN POPULATION

WCN25-1187 Clinical and Histopathological profile of lupus nephritis patients at tertiary care center in central India

WCN25-1187 Clinical and Histopathological profile of lupus nephritis patients at tertiary care center in central India

Epidemiological profile of kidney transplant patients with lupus nephritis.

Lupus nephritis (LN) affects up to 50% of patients with systemic lupus erythematosus (SLE) and may lead to kidney failure and require kidney transplantation (KT). Results compared to KT from other causes are controversial, and we aimed to assess the clinical course, complications, and survival of LN patients undergoing KT. Retrospective cohort of 99 KT due to LN from 1977 to 2023 at a single center, divided into two groups according to the immunosuppression period: G1 (before 2009) and G2 (from 2009 onwards). Clinical and demographic characteristics, as well as clinical evolution, were compared. Patients were predominantly white (65.9%), female (86.9%), in their first KT (83.8%). The median age was 20.0 (11.5-25.0) years at SLE diagnosis, and 30.0 (23.0-40.0) years at KT. Renal graft biopsy was indicated in 46% of patients, with rejection observed in 23%, and LN recurrence in 5%. When assessing the two distinct periods of standard immunosuppression, there was no difference in median glomerular filtration rate and proteinuria at 1 and 5 years, nor in 5-year survival. Throughout follow-up, 37.4% of patients lost their graft, and 13% died with a functioning graft. No graft loss was attributed to LN recurrence. KT is a successful treatment for LN, with graft survival rates similar to those of transplants from other causes. LN recurrence was not associated with renal graft loss.

Identification and validation of key autophagy-related genes in lupus nephritis by bioinformatics and machine learning.

Lupus nephritis (LN) is one of the most frequent and serious organic manifestations of systemic lupus erythematosus (SLE). Autophagy, a new form of programmed cell death, has been implicated in a variety of renal diseases, but the relationship between autophagy and LN remains unelucidated. We analyzed differentially expressed genes (DEGs) in kidney tissues from 14 LN patients and 7 normal controls using the GSE112943 dataset. Key modules and their contained genes were identified utilizing weighted gene co-expression network analysis (WGCNA). Differentially expressed autophagy-related genes (DE-ARGs) among DEGs, key module genes and autophagy-related genes (ARGs) were obtained by venn plot, and subjected to protein-protein interaction network construction. Two machine learning methods were applied to identify signature genes. The area under the receiver operating characteristic (ROC) curves was used to assess the accuracy of the signature genes. We also analyzed immune cell infiltration in LN. Additionally, the association between key genes and kidney diseases was predicted. Finally, key genes expression in kidney was verified by clinical samples and animal experiments. A total of 10304 DEGs were identified in GSE1129943 and 29 modules were identified in WGCNA. Among them, the brown module and coral 2 module exhibited significant correlation with LN (cor = 0.86, -0.84, p<0.001). Machine learning techniques identified 5 signature genes, but only 2 were validated in the external dataset GSE32591, namely MAP1LC3B (AUC = 0.920) and TNFSF10 (AUC = 0.937), which are involved in autophagy and apoptosis. Immune infiltration analysis suggested that these key genes may be associated with immune cell infiltration in LN. In addition, these genes have been linked to a variety of renal diseases, and their expression was verified in kidney tissues in LN patients and lupus mice. MAP1LC3B and TNFSF10 may be key autophagy-related genes in LN. These key genes have the potential to provide new insights into the molecular diagnosis and treatment of LN.

Steroid-induced diabetes in lupus nephritis patients: Classic risk factors or a different type of diabetes?

Glucocorticoids are frequently employed in systemic lupus erythematosus (SLE) patients and play a critical role in the induction therapy of lupus nephritis (LN), despite their many side effects, including steroid-induced diabetes (SID). Information regarding SID in SLE patients is quite scant. The aim of this study was to determine risk factors associated with the development of SID in patients with LN. A nested case-control study was conducted. We included patients with biopsy-proven LN, who received induction treatment with steroids. Out of the total of 358 patients, 35 (9.7%) developed SID. Patients with SID had more metabolic risk factors, including the metabolic score for insulin resistance (METS-IR); more factors related with lupus activity, with higher SLEDAI and SLICC-DI scores; and lower cumulative pre-induction steroid dose. A higher percentage of patients who developed SID received steroid pulses and a lower percentage received antimalarials. After logistic regression, the variables significantly associated with the development of SID were the SLEDAI index (OR 1.25 [95% CI 1.04-1.50], p 0.01), SLICC-DI (OR 4.93 [95% CI 2.14-11.3], p < 0.001), METS-IR (OR 1.17 [95% CI 1.04-1.32], p 0.009), delta METS-IR at 6months (OR 1.20 [95% CI 1.03-1.39], p 0.01), and the use of antimalarials (OR 0.14, [95% CI 0.02-0.85], p 0.03). After propensity score matching, METS-IR remained a significant predictor of SID. Patients with METS-IR >36.8 were at higher risk (OR: 2.83, 95% CI: 1.09-7.36, p = 0.034). In conclusion, SDI development in patients receiving induction therapy for LN is associated with both classic metabolic risk factors and SLE-specific factors, and antimalarial use could be associated with a protective effect. Rheumatologists should be aware of this potential complication, in order to implement appropriate management strategies.

Clinicopathological characteristics and prognosis of lupus nephritis patients with positive anti-ribonucleoprotein antibodies.

Positive anti-ribonucleoprotein antibodies may characterizea subgroup of patients affected bylupus nephritis with mild kidney damage, but little is known about their clinical features and long-term prognosis. Patients were retrospectively selected from the lupus nephritis database ( http://ln.medidata.cn ) of the First Affiliated Hospital of Sun Yat-sen University between 2006 and 2011. Logistic regression analysis identified the clinicopathological indicators related to positive anti-ribonucleoprotein antibodies. Additionally, the Cox proportional hazard regression model was used to assess the association of baseline variables with clinical outcomes. Of the 485 enrolled patients, 184 (37.9%) tested positive for anti-ribonucleoprotein antibodies. The group with positive anti-ribonucleoprotein antibodies exhibited a higher prevalence of rash, photosensitivity, and Raynaud's phenomenon, and lower scores on the systemic lupus erythematosus disease activity index (SLEDAI) and the Activity Index scores in kidney biopsies. It is important to note that, although proteinuria did not differ, patients with anti-ribonucleoprotein positivity had a lower prevalence of hematuria and cylindruria, and a higher estimated glomerular filtration rate than patients without anti-ribonucleoprotein antibodies. After a median follow-up of approximately 170months, no significant differences were observed in kidney or patient survival between groups. Lupus nephritis patients with anti-ribonucleoprotein antibodies present milder kidney damage and more dermatological manifestations. Despite the negative correlation between anti-ribonucleoprotein antibodies and both SLEDAI and activity index scores, these antibodies may not be predictive of better kidney outcomes.

Distinct genetic risk loci between biopsy-proven renal and non-renal lupus: a 10-year longitudinal cohort.

Systemic lupus erythematosus (SLE) is a heterogeneous disease which manifests as different subphenotypes. Distinct subphenotypes, such as lupus nephritis (LN), have been associated with increased genetic risk, but prior studies have been limited by cross-sectional and imprecisely subphenotyped cohorts. This study investigated the genetic basis for LN using a longitudinal cohort of distinctly subphenotyped patients. SLE patients with biopsy-proven LN or never developed LN (NLN) were recruited from 8 tertiary referral centres. All patients had longitudinal clinical data for at least 10-years, or died during the study period. NLN patients had no renal involvement for at least 10-years. Subjects were genotyped and polygenic risk scores (PRS) were calculated using 230 SLE-associated SNPs. Genome-wide association analyses were also conducted for LN-vs-control, NLN-vs-control, and LN-vs-NLN comparisons, along with heterogeneity tests to assess differences in effect size. Among 1462 patients, 824 (56%) and 638 (43%) had LN and NLN, respectively. PRS was significantly higher in the LN cohort. Genome-wide significant variants were identified in HLA, TNFAIP3, BLK, and STAT4 loci specifically for LN patients, while STAT4 also remained significant for NLN patients. Direct LN-vs-NLN associations showed no statistically significant variants but heterogeneity tests revealed other genetic loci, including ELF1, OX40, DUSP22, and TPCN2. Different subphenotypes of SLE are predisposed by distinct genetic risk loci, which can only be identified in clearly subphenotyped cohorts with sufficient longitudinal data. We identified unique genetic risk loci enriched among patients with biopsy-proven LN, and postulate that individual subphenotypes may have varying genetic predisposition.

Outcomes following immunosuppressive therapy withdrawal after complete renal response in proliferative lupus nephritis

ObjectiveTo investigate the rate and factors influencing renal relapse (RR) in proliferative lupus nephritis (LN) patients who discontinued immunosuppressive therapy (IST), as well as the long-term renal outcomes following RR.MethodsRetrospective,...

Utility of Non-albumin Proteinuria for the Assessment of the Severity of Tubulointerstitial Inflammation in Lupus Nephritis Patients

Utility of Non-albumin Proteinuria for the Assessment of the Severity of Tubulointerstitial Inflammation in Lupus Nephritis Patients

Nomogram for predicting proliferative lupus nephritis in patients with low-level proteinuria.

Proliferative lupus nephritis (LN) is not uncommon in individuals with proteinuria < 0.5 g/24h, highlighting the importance of predicting proliferative nephritis for effective clinical management. We aimed to develop a predictive model for proliferative nephritis in this population. The enrolled 671 biopsy-proven LN patients were divided into low-level proteinuria (< 0.5 g/24 h) and high-level proteinuria (≥ 0.5 g/24 h) groups. The clinical features, pathological characteristics and long-term outcomes of the two groups were compared. The least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression analysis were used to construct a predictive nomogram for proliferative nephritis in low-level proteinuria patients and internal validation was performed using bootstrap-resampling. 103 of 671 (15.4%) LN patients had low-level proteinuria, while 43 (41.7%) of whom showed proliferative LN, and the activity index and chronicity index were 5 (IQR [4,7]) and 3 (IQR [2,4]), respectively. The long-term adverse renal events-free survival was preferable in the low-level proteinuria group. The LASSO-logistic regression identified that age, sex, mean arterial pressure, haemoglobin, platelet, 24-h proteinuria and anti-double strands DNA antibodies positivity were associated with proliferative nephritis in those with low-level proteinuria. The predictive model showed an area under curve of 0.900 (95% CI: 0.840-0.960) and a bootstrapped result of 0.894 (95% CI: 0.832-0.965), with good calibration. 41.7% of the patients with low-level proteinuria exhibited proliferative LN when biopsied. The nomogram including clinical, urinary, and laboratory parameters might help with the prediction of proliferative LN before biopsy among patients with low-level proteinuria.

Developing a Label-Free Infrared Spectroscopic Analysis with Chemometrics and Computational Enhancement for Assessing Lupus Nephritis Activity.

Patterns of disease and therapeutic responses vary widely among patients with autoimmune glomerulonephritis. This study introduces groundbreaking personalized infrared (IR)-based diagnostics for real-time monitoring of disease status and treatment responses in lupus nephritis (LN). We have established a relative absorption difference (RAD) equation to assess characteristic spectral indices based on the temporal peak heights (PHs) of two characteristic serum absorption bands: ν1 as the target signal and ν2 as the PH reference for the ν1 absorption band, measured at each dehydration time (t) during dehydration. The RAD gap (Ψ), defined as the difference in the RAD values between the initial and final stages of serum dehydration, enables the measurement of serum levels of IgG glycosylation (ν1 (1030 cm-1), ν2 (1171 cm-1)), serum lactate (ν1 (1021 cm-1), ν2 (1171 cm-1)), serum hydrophobicity (ν1 (2930 cm-1), ν2 (2960 cm-1)), serum hydrophilicity (ν1 (1550 cm-1), ν2 (1650 cm-1)), and albumin (ν1 (1400 cm-1), ν2 (1450 cm-1)). Furthermore, this IR-based assay incorporates an innovative algorithm and our proprietary iPath software (ver. 1.0), which calculates the prognosis prediction function (PPF, Φ) from the RAD gaps of five spectral markers and correlates these with conventional clinical renal biomarkers. We propose that this algorithm-assisted, IR-based approach can augment the patient-centric care of LN patients, particularly by focusing on changes in serum IgG glycosylation.

Safety Profile of SARS-CoV-2 Vaccination in Patients with Lupus Nephritis: A Retrospective Study.

Objectives: Vaccination against SARS-CoV-2 has been vital in alleviating the spread of the recent pandemic. We aimed to estimate the frequency and type of adverse events related to SARS-CoV-2 vaccine in patients with lupus nephritis (LN), and assess its impact, if any, on the risk of subsequent reactivation of nephritis. Methods: This was a retrospective, multicenter study which included patients with biopsy-proven LN, who had received at least one vaccine dose. Patients who ended up with end-stage kidney disease (ESKD) prior to vaccination or were diagnosed with LN after vaccination were excluded. Adverse events, systemic or local, COVID-19 outcomes (full recovery, death, or long COVID-19), outcome of LN (remission, refractory disease, relapse, ESKD or death), demographics, laboratory measurements, and immunosuppressive regimens were recorded. Results: Sixty-seven patients were included. The median age was 33 (20-46) years. Induction therapy for LN was administered to 92.5% of patients and 74.6% received maintenance therapy. Of these, 94.02% were in remission at vaccination. The BNT162b2 mRNA vaccine was administered in 97.01% of cases, with mild systemic adverse symptoms in 28.35% (myalgias 17.91%, headache 13.43%, arthralgias 13.43%, and fever 10.44%) and local adverse effects in 35.82% (pain 25.37%, swelling 13.43%). Overall, among patients in remission upon vaccination, two (3.17%) experienced a LN relapse within 5.75 (±0.25) months, while 75% of those with active disease at vaccination achieved remission within 21 (±2) months. Conclusions: SARS-CoV-2 vaccination appears safe for LN patients without serious adverse events occurring, and there is no significant impact in the clinical course of the disease.

Interleukin-32 positive immune and resident cells in kidney samples from lupus patients: a pilot study.

Lupus nephritis (LN), caused by immune complexes produced in situ or deposited from the bloodstream, is one of the most severe features of Systemic Lupus Erythematosus (SLE) leading to an increased morbidity and mortality. Toll like receptors (TLRs), such as TLR3, TLR7 and TLR9, may play a key role in its pathogenesis. Interleukin-32 (IL-32), a cytokine involved in both innate and adaptive immune responses, has been widely considered in autoimmune-inflammatory rheumatic diseases. This study aims to evaluate the IL-32 role in LN, also investigating the effect of LN patients IgG (LN-IgG) on IL-32 production via TLR3. In LN patients, IL-32 was detected in sera samples by ELISA KIT and in kidney tissue by immunohistochemistry. HEK293/T3 cells were incubated with LN-IgG and analyzed for TBK1, phospho-p65 NF-κB and IL-32 by Western blot. We demonstrated IL-32 presence in LN patients compared to SLE patients without renal involvement, observing a direct correlation between IL-32 serum levels and disease duration (p=0.02; r 0.2978). Moreover, IL-32 was strongly expressed in renal samples of LN patients. Phosphorylation of TBK1 resulting in NF-κB activation and IL-32 increase was observed in HEK293/T3 cells following LN-IgG treatment, TLR3 inhibitor using induced a significant reduction in the expression of these molecules. These results showed that IL-32 is up-regulated in the kidney of LN patients suggesting that in renal tissue IL-32 expression could be induced through TLR3 activation by the LN patients' antibodies. This study may indicate a possible role for IL-32 in the pathogenesis of LN.

Urinary congophilia as a predictive biomarker of lupus nephritis in pregnant and non-pregnant women with systemic lupus erythematosus.

Endoplasmic reticulum stress with protein misfolding has been introduced as a key pathogenetic mechanism in lupus nephritis (LN). Pregnancy is thought to exaggerate proteostasis, which leads to the accumulation of potentially pathogenic misfolded proteins in the urine, serum, and placenta particularly in women with preeclampsia. The detection of misfolded proteins is made using Congo red stain, which is referred to as congophilia. This study aimed to assess the predictive value of urinary congophilia as a marker of LN activity in pregnant and non-pregnant LN women. Urine samples from non-pregnant LN women (n = 45), pregnant LN women (n = 12), as well as pregnant healthy controls (n = 38) were collected. Urinary congophilia was assessed by Congo Red Dot Blot assay. The disease activity was defined according to SLE Disease Activity Index (SLEDAI) score, and SLE Disease Activity Index-Renal Domain (SLEDAI-R) score. Renal biopsy was done for 33 non-pregnant LN women as it was clinically indicated, and modified NIH activity index (AI) was assessed according to the classification of LN by the International Society of Nephrology/Renal Pathology Society (ISN/RPS). Congo red retention (CRR) values were significantly higher for pregnant active LN patients, in comparison with pregnant inactive LN patients (p = .014), as well as pregnant healthy controls (p = .009). Additionally, CRR values were significantly higher for non-pregnant active LN patients, in comparison with non-pregnant inactive LN patients (p = .016), as well as pregnant healthy controls (p ≤ .001). There were significant positive correlations between CRR on one hand, and anti-ds-DNA (r = 0.791, p ≤ .001), serum creatinine (r = 0.620, p ≤ .001), SLEDAI score (r = 0.623, p ≤ .001), as well as SLEDAI-R score (r = 0.473, p = .005) on the other hand. A highly significant negative correlation was detected between CRR, and serum albumin (r = -0.454, p = .001). CRR at a cut point ≥21.85 had 83% sensitivity, and 58% specificity to capture high LN activity status (NIH-AI >10) versus lower LN activity status. Urinary congophilia may add a diagnostic value in patients with LN and can be a reliable marker of disease activity. CRR is related to disease activity rather than pregnancy.

Urine KIM-1 as Predictor of Renal Histopathology and Treatment Response in Lupus Nephritis Patients

Urine KIM-1 as Predictor of Renal Histopathology and Treatment Response in Lupus Nephritis Patients

Nailfold capillaroscopic changes in patients with glomerular diseases.

Glomerulonephritis is a heterogenous group of diseases which is diagnosed mainly by renal biopsy. This study aims to assess nailfold capillaroscopic changes in patients with glomerular diseases. This study was conducted on 50 patients with glomerular disease confirmed by renal biopsy and 50 age and sex matched healthy controls. Clinical, laboratory evaluation and nailfold capillaroscopic examination were done for all participants. Lupus nephritis was the most common pathological type among glomerulonephritis group [17 (34%)], followed by focal segmental glomerulosclerosis [9 (18%)]. Tortuous capillaries were significantly higher in patients with primary glomerular diseases compared to healthy persons (92.9% vs 58%, P<0.001). The diameter was significantly lower in patients with primary glomerular diseases compared to healthy control group (15.6μm vs 18.9μm, P=0.001). Subpapillary venous plexus (28.6% vs 6%, P=0.02) and capillary microhemorrhage (32% vs 0%, P<0.001) were significantly more frequent in patients with primary glomerular diseases compared to the control group. Patients with lupus nephritis had higher capillary diameter (19.5 vs 15.6μm, P=0.02), width (55.6 vs 44μm, P=0.003) and microhemorrhage (64.7% vs 32%, P=0.03) compared to patients with primary glomerulonephritis. There was a statistically significant difference as regard diameter (P=0.005) and length (P=0.02) between different classes of lupus nephritis. More tortious capillaries and lower capillary diameter were found in patients with primary glomerular disease compared to healthy persons. Lupus nephritis patients had more dilated capillaries and more capillary microhemorrhage compared to primary glomerulonephritis patients.

Serum antineutrophil cytoplasmic antibody positivity at the time of renal biopsy is associated with disease activity of lupus nephritis

Objective To investigate the correlations between serum antineutrophil cytoplasmic antibody (ANCA) and clinicopathological features, induction treatment response, and prognosis of lupus nephritis (LN) patients. Methods In this retrospective study, biopsy-proven LN patients from October 2010 to September 2020 were tested for serum ANCA by indirect immunofluorescence and ELISA and were divided into ANCA-positive group and ANCA-negative group. The clinicopathological data of the two groups were analyzed and compared. Results Thirty-five of 115 patients (30.43%) were seropositive for ANCA. ANCA-positive patients had significantly higher systemic lupus erythematosus activity index and activity index scores, higher 24-h urinary protein, and lower complement three levels (p = 0.001, 0.028, 0.023, 0.009, respectively). The incidences of oral ulcers, thrombocytopenia, and leukocyturia, and the positive rates of anti-dsDNA antibody and anti-histone antibody were significantly higher in ANCA-positive group (p = 0.006, 0.019, 0.012, 0.001, 0.019, respectively). Class IV LN and fibrinoid necrosis/karyorrhexis were significantly more common in the ANCA-positive group (p = 0.027, 0.002). There was no significant difference in the total remission rate of ANCA-positive patients receiving cyclophosphamide and mycophenolate mofetil as induction therapies (83.33% vs. 66.67%, p > 0.05), while patients receiving cyclophosphamide as induction therapy had a higher total remission rate than those receiving other immunosuppressants (83.33% vs. 20%, p = 0.028). Conclusions LN patients with ANCA seropositivity at renal biopsy have a significantly higher disease activity, and their pathological manifestations are predominantly proliferative LN. These patients require a more active immunosuppressive therapy with cyclophosphamide or mycophenolate mofetil to improve their remission rate.

Exploring potential multiple molecular biomarkers that predict treatment response in patients with lupus nephritis

Limited knowledge exists regarding biomarkers that predict treatment response in Lupus nephritis (LN). We aimed to identify potential molecular biomarkers to predict treatment response in patients with LN. We enrolled 66 patients with active LN who underwent renal biopsy upon enrollment. Serum and urine samples were collected longitudinally, and we measured 12 biomarkers in each sample using a multiplex immunofluorescence assay. These biomarkers included monocyte chemoattractant protein-1 (MCP-1), interferon gamma-induced protein 10 (IP-10), interferon-γ (IFN-γ), interleukin 6 (IL-6), interleukin 16 (IL-16), interleukin 17 (IL-17), interleukin 23 (IL-23), tumor necrosis factor receptor II (TNF-RII), vascular cell adhesion molecule 1 (VCAM-1), retinol-binding protein 4 (RBP 4), vitamin D binding protein (VDBP), and neutrophil gelatinase-associated lipocalin (NGAL). Patients were categorized into two groups based on their 1-year treatment response to Mycophenolate mofetil (MMF)-based therapy: 50 responders and 16 non-responders. Only urine IL-17 (uIL-17) showed baseline level differences between the two groups, with higher in responders. In ROC curve analyses assessing the predictive performance of biomarkers, baseline uIL-17 and changes in uIL-6 and uIL-23 levels at 3 months could predict the 1-year treatment response, showing AUC values of 0.70 (95% CI 0.54–0.87), 0.70 (0.54–0.86), and 0.71 (0.57–0.85), respectively. Combining uIL-6 and uIL-23 into a model improved predictability, achieving an AUC of 0.75 (0.61–0.90). Baseline uIL-17 levels and early changes in uIL-6 and uIL-23 could serve as potential biomarkers to predict 1-year treatment response in lupus nephritis patients receiving MMF-based therapy.

Identification of two distinct clusters in membranous lupus nephritis patients: recognition of a high-risk profile based on unsupervised analysis.

Membranous lupus nephritis (MLN) traditionally includes class V (alone) and may be associated with other classes (III or IV). The clinical, therapeutic and prognosis relevance of the classification remains controversial. A retrospective cohort of 412 MLN patients from the First Affiliated Hospital of Sun-Yat Sen University was followed for a median of 65.68 (IQR: 23.13-131.70) months. The primary outcomes were adverse renal events including all-cause death and end-stage renal diseases (ESRD). Phenotypes were identified and validated using unsupervised clustering analysis (K-means), Principal component analysis (PCA) and decision tree analysis. Distinct clinical and pathological differences were noted for the traditional Class IV+V, the traditional Class V+III and Class V exhibited high similarities in clinical features and prognosis (P=0.074). K-means clustering revealed high-risk (n=180) and low-risk groups (n=232), with significant differences in adverse renal outcomes (9.2%vs. 4.1%, P<0.001). To recognize the high-risk profile of MLN patients, a decision tree based on Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Score, hemoglobin, serum creatinine, traditional classification, and activity index of renal biopsy accurately clustered patients in the development (95.8% accuracy) and validation (87.1% accuracy) cohorts. Two novel phenotypic clusters, more predictive than traditional classifications, enhance high-risk profile identification and prognostic accuracy.

Outcomes of a 12-month course of early and late rituximab BCD020 biosimilar administration in juvenile systemic lupus erythematosus: A retrospective study.

Juvenile systemic lupus erythematosus (SLE) is a severe, life-threatening disease. However, the role of rituximab in managing juvenile SLE remains undefined, although early biological intervention may improve disease outcomes. To assess the differences in the outcomes of different types of rituximab administration (early and late). In this retrospective cohort study, the information of 36 children with SLE with early (less than 6 months from onset) rituximab administration (ERA), and late (more than 1 year) rituximab administration (LRA) was analyzed. We compared initial disease characteristics at onset, at baseline (start of rituximab), and at the end of the study (EOS) at 12 months, as well as outcomes and treatment characteristics. The main differences at baseline were a higher daily median dose of corticosteroids, increased MAS frequency, and a higher Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) in the ERA group. No differences in the main SLE outcomes between groups at the EOS were observed. The part of lupus nephritis patients who achieved remission changed from 44% to 31% in ERA and 32% to 11% in the LRA group. Patients with ERA had a shorter time to achieve low daily corticosteroid dose (≤ 0.2 mg/kg) at 1.2 (0.9; 1.4) years compared to 2.8 (2.3; 4.0) years (P = 0.000001) and higher probability to achieve this low dose [hazard ratio (HR) = 57.8 (95% confidence interval (CI): 7.2-463.2), P = 0.00001 and remission (SLEDAI = 0); HR = 37.6 (95%CI: 4.45-333.3), P = 0.00001]. No differences in adverse events, including severe adverse events, were observed. ERA demonstrated a better steroid-sparing effect and a possibility of earlier remission or low disease activity, except for lupus nephritis. Further investigations are required.