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Introduction: High-dose glucocorticoid (GC)-based dual immunosuppressive treatment regimens are still frequently used in active lupus nephritis (LN) despite their known association with dose-dependent toxicities and incomplete efficacy. We hypothesised that the addition of voclosporin to low-dose GCs and mycophenolate mofetil (MMF) would reduce exposure to the toxicities of high-dose GC-based dual immunosuppressive therapy regimens, resulting in an improved safety profile without compromising efficacy., Methods: Propensity score matching generated two groups of matched participants from the voclosporin arms (in combination with MMF (2 g/day) and low-dose GCs) of the Phase 2 AURA-LV and Phase 3 AURORA 1 studies and the MMF (3 g/day) and intravenous cyclophosphamide (IVC) arms (both in combination with high-dose GCs) of the Aspreva Lupus Management Study (ALMS) induction study. Safety and efficacy outcomes were assessed over 6 months., Results: There were 179 matched participants identified between the AURA-LV/AURORA 1 studies and ALMS. The overall incidence of adverse events (AEs) was higher in IVC- and MMF-treated participants of ALMS; more voclosporin-treated participants reported AEs by preferred term of glomerular filtration rate decreased, hypertension and anaemia. The incidence of serious AEs was similar across treatments. There were four (2.2%) deaths in IVC- and MMF-treated participants of ALMS compared with seven (3.9%) deaths in voclosporin-treated participants. Significantly more voclosporin-treated participants achieved a ≥25% reduction in urine protein creatinine ratio (UPCR) from baseline at 3 months and ≥50% reduction in UPCR from baseline at 6 months., Conclusions: Compared with the high-dose GC-based regimens used in ALMS, voclosporin-based triple immunosuppressive therapy resulted in fewer AEs overall and greater and earlier reductions in proteinuria over the first 6 months of treatment. These data reinforce the feasibility of using low doses of GCs and MMF to treat LN when combined with voclosporin as a third agent., Competing Interests: Competing interests: MD has received grants or contracts from Annexon Biosciences and GSK plc and is a consultant for Annexon Biosciences, AstraZeneca, Aurinia Pharmaceuticals Inc., Biogen, GSK plc and Pfizer. KK has received grants of contracts from UCB and Novartis and is a consultant for BMS, GSK plc, Biogen, AstraZeneca, Equillium, Artiva, Pfizer, Eli Lilly, Gilead and Kyverna. NS is a former employee and shareholder of Aurinia Pharmaceuticals Inc. MT is a consultant for Aurinia Pharmaceuticals Inc. LSH and EY are employees and shareholders of Aurinia Pharmaceuticals Inc. ADA is a consultant for Aurinia Pharmaceuticals Inc., AstraZeneca, GSK plc and Eli Lilly., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Trauma history is associated with SLE onset and worse patient-reported outcomes; perceived stress is associated with greater SLE disease activity. Stress perceptions vary in response to life events and may be influenced by psychosocial factors. In an SLE cohort, we examined whether stressful events associated with perceived stress, whether psychosocial factors affected perceived stress, and whether these relationships varied by prior trauma exposure., Methods: This is a cross-sectional analysis of data from the California Lupus Epidemiology Study, an adult SLE cohort. Multivariable linear regression analyses controlling for age, gender, educational attainment, income, SLE damage, comorbid conditions, glucocorticoids ≥7.5 mg/day and depression examined associations of recent stressful events (Life Events Inventory) and positive (resilience, self-efficacy, emotional support) and negative (social isolation) psychosocial factors with perceived stress. Analyses were stratified by lifetime trauma history (Brief Trauma Questionnaire (BTQ)) and by adverse childhood experiences (ACEs) in a subset., Results: Among 242 individuals with SLE, a greater number of recent stressful events was associated with greater perceived stress (beta (95% CI)=0.20 (0.07 to 0.33), p=0.003). Positive psychosocial factor score representing resilience, self-efficacy and emotional support was associated with lower perceived stress when accounting for number of stressful events (-0.67 (-0.94 to -0.40), p<0.0001); social isolation was associated with higher stress (0.20 (0.14 to 0.25), p<0.0001). In analyses stratified by BTQ trauma and ACEs, associations of psychosocial factors and perceived stress were similar between groups. However, the number of recent stressful events was significantly associated with perceived stress only for people with BTQ trauma (0.17 (0.05 to 0.29), p=0.0077) and ACEs (0.37 (0.15 to 0.58), p=0.0011)., Conclusion: Enhancing positive and lessening negative psychosocial factors may mitigate deleterious perceived stress, which may improve outcomes in SLE, even among individuals with a history of prior trauma who may be more vulnerable to recent stressful events., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: There is a lack of data on the use of telemedicine (TM) in SLE. SLE outcome measures remain complex, and clinicians and clinical trialists have raised concerns about the accuracy of virtual disease activity measures. This study evaluates the level of agreement between virtual SLE outcome measures and face-to-face (F2F) encounter. Here, we describe the study design, virtual physical examination protocol and demographics for the first 50 patients evaluated., Methods and Analysis: This is an observational, longitudinal study of 200 patients with SLE with varying levels of disease activity from 4 academic lupus centres serving diverse populations. Each study participant will be evaluated at a baseline and a follow-up visit. At each visit, participants are evaluated by the same physician first via a videoconference-based TM and then a F2F encounter. For this protocol, virtual physical examination guidelines relying on physician-directed patient self-examination were established. SLE disease activity measures will be completed immediately after the TM encounter and repeated after the F2F encounter for each visit. The degree of agreement between TM and F2F disease activity measures will be analysed using the Bland-Altman method. An interim analysis is planned after the enrolment of the first 50 participants., Ethics and Dissemination: This study has been reviewed by the Columbia University Medical Center Institutional Review Board (IRB Protocol #: AAAT6574). The full results of this study will be published after the final data analysis of 200 patients. The abrupt shift to TM visits due to the COVID-19 pandemic disrupted clinical practice and clinical trials. Establishing a high level of agreement between SLE disease activity measures obtained with videoconference TM and F2F at the same time point, will allow for improved assessment of disease activity when F2F data cannot be acquired. This information may guide both medical decision-making and provide reliable outcome measures for clinical research., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: In lupus nephritis the pathological diagnosis from tissue retrieved during kidney biopsy drives treatment and management. Despite recent approval of new drugs, complete remission rates remain well under aspirational levels, necessitating identification of new therapeutic targets by greater dissection of the pathways to tissue inflammation and injury. This study assessed the safety of kidney biopsies in patients with SLE enrolled in the Accelerating Medicines Partnership, a consortium formed to molecularly deconstruct nephritis., Methods: 475 patients with SLE across 15 clinical sites in the USA consented to obtain tissue for research purposes during a clinically indicated kidney biopsy. Adverse events (AEs) were documented for 30 days following the procedure and were determined to be related or unrelated by all site investigators. Serious AEs were defined according to the National Institutes of Health reporting guidelines., Results: 34 patients (7.2%) experienced a procedure-related AE: 30 with haematoma, 2 with jets, 1 with pain and 1 with an arteriovenous fistula. Eighteen (3.8%) experienced a serious AE requiring hospitalisation; four patients (0.8%) required a blood transfusion related to the kidney biopsy. At one site where the number of cores retrieved during the biopsy was recorded, the mean was 3.4 for those who experienced a related AE (n=9) and 3.07 for those who did not experience any AE (n=140). All related AEs resolved., Conclusions: Procurement of research tissue should be considered feasible, accompanied by a complication risk likely no greater than that incurred for standard clinical purposes. In the quest for targeted treatments personalised based on molecular findings, enhanced diagnostics beyond histology will likely be required., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Although an early decrease in proteinuria has been correlated with good long-term renal outcome in lupus nephritis (LN), studies aimed at defining a cut-off proteinuria value are missing, except a recent analysis performed on patients randomised in the Euro-Lupus Nephritis Trial, demonstrating that a target value of 0.8 g/day at month 12 optimised sensitivity and specificity for the prediction of good renal outcome. The objective of the current work is to validate this target in another LN study, namely the MAINTAIN Nephritis Trial (MNT)., Methods: Long-term (at least 7 years) renal function data were available for 90 patients randomised in the MNT. Receiver operating characteristic curves were built to test the performance of proteinuria measured within the 1st year as short-term predictor of long-term renal outcome. We calculated the positive and negative predictive values (PPV, NPV)., Results: After 12 months of treatment, achievement of a proteinuria <0.7 g/day best predicted good renal outcome, with a sensitivity and a specificity of 71% and 75%, respectively. The PPV was high (94%) but the NPV low (29%). Addition of the requirement of urine red blood cells ≤5/hpf as response criteria at month 12 reduced sensitivity from 71% to 41%., Conclusions: In this cohort of mainly Caucasian patients suffering from a first episode of LN in most cases, achievement of a proteinuria <0.7 g/day at month 12 best predicts good outcome at 7 years and inclusion of haematuria in the set of criteria at month 12 undermines the sensitivity of early proteinuria decrease for the prediction of good outcome. The robustness of these conclusions stems from the very similar results obtained in two distinct LN cohorts., Trial Registration Number: NCT00204022.

Objective: To identify factors associated with clinical outcome in patients with lupus nephritis., Methods: Data from the Aspreva Lupus Management Study (ALMS) were analysed. Using multivariate analysis, we assessed the prognostic value of demographic, clinical, laboratory and histopathological features on the frequency of either complete remission (CR) or treatment failure (TF) during the maintenance phase., Results: Among the 370 subjects who entered the trial (complete population), non-Hispanic ethnicity was associated with a higher likelihood of CR (OR=2.0). Several factors were independently associated with a greater likelihood of TF, including: (1) anti-double-stranded DNA (anti-dsDNA) at trial entry (OR=12.7), (2) failure to reduce anti-dsDNA within 8 weeks (OR=2.9) and (3) failure to reduce urine protein:creatinine ratio (UP/C) by ≥25% within 8 weeks (OR=2.6). Among the 227 subjects who entered the maintenance phase (maintenance population), baseline estimated glomerular filtration rate (eGFR) ≥90 mL/min/1.73 m(2) was associated with a greater likelihood of CR (OR=2.0), and UP/C >1 at the end of induction was associated with a lower likelihood of CR (OR=0.3). Induction treatment with intravenous cyclophosphamide (IVC) was associated with a lower likelihood of TF (OR=0.5), while lack of treatment with antimalarials (OR=2.4), failure to reduce anti-dsDNA during the first 8 weeks of induction (OR=3.5), failure to reduce UP/C during the first 8 weeks of induction (OR=2.1) and anti-dsDNA positivity at the end of induction (OR=8.3) were independently associated with a greater likelihood of TF., Conclusions: This analysis demonstrates that levels of anti-dsDNA and UP/C during induction treatment are independently associated with renal outcome over the ensuing 3 years in both the complete and maintenance populations. Ethnicity is associated with renal outcome in just the complete population, and eGFR, induction treatment and treatment with antimalarials are associated with renal outcome in just the maintenance population.