Use of belimumab in treating patients with systemic lupus erythematosus: a single-center, real-world retrospective study.

OBJECTIVE: To investigate the efficacy and safety of belimumab in the treatment of systemic lupus erythematosus (SLE) in a real-world setting and provide a valuable reference for clinical treatment. METHODS: In this retrospective study, 101 patients with SLE who came to our hospital from March 2020 to September 2022, 56 of whom with lupus nephritis (LN), were selected. All patients received belimumab in combination with standard of care(SoC)therapy regimen for more than 52 weeks and their clinical/laboratory data, assessment of disease activity, glucocorticoids dosage and occurrence of adverse events were recorded. Lupus Low Disease Activity State (LLDAS) and DORIS remission as a primary goal in the treatment of SLE. The groups were classified according to the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2 K): SLEDAI-2 K < 6 was categorized as the mild group (mild activity) and SLEDAI-2 K ≥ 6 was categorized as the active group (moderate-severe activity). The disease of the two groups mentioned above were assessed using the SELENA-SLEDAI Flare Index (SFI) and the SLE Responder Index-4 (SRI-4), respectively. Furthermore, we used complete remission (CR) and partial remission (PR) in the kidney as the standard for efficacy evaluation for LN patients. RESULTS: After 52 weeks of treatment with belimumab, patients' complement levels increased significantly (p < 0.05); Other indicators such as 24-hour urine protein quantification and daily glucocorticoids dose decreased compared to pretreatment (p < 0.05). At 52 weeks, (i) after evaluation, the whole group of patients showed significant improvement in their condition; (ii) 55.4% of patients achieved LLDAS and 23.8% achieved DORIS remission; (iii) 73.2% of patients with LN achieved CR, 16.1% achieved PR. Adverse reactions were observed in 15 patients (14.9%), all of which normalized after symptomatic treatment. CONCLUSIONS: In general, during treatment with belimumab, immunological and biochemical indices improved in SLE patients, urinary protein levels were reduced in LN patients, and the rate of renal function remission was effectively increased; At the same time, the use of belimumab is associated with a low frequency of side effects, good overall tolerability and a favorable safety profile.

Clinical outcomes in lupus nephritis patients treated with belimumab in real-life setting: a retrospective comparative study in China.

Objective: The use of belimumab in treating lupus nephritis (LN) patients in China is still in its early stages. This retrospective comparative study aims to delineate the disease activity, associated therapies, clinical outcomes, and adverse events among LN patients treated with belimumab, reflecting real-world experience in southeastern China. Methods: From May 2020 to December 2023, 54 LN patients treated with belimumab and 42 LN patients treated with conventional therapy were enrolled. All patients had a follow-up period of more than 3 months. The general information, presenting clinical and laboratory data, and outcomes were collected and compared. Results: At 3 months of belimumab treatment, compared to baseline, there was a decrease in proteinuria from 74.1% to 64.8% (p < 0.001), a reduction in hematuria from 59.3% to 37.0% (p = 0.008), and an increase in partial or complete renal response from 53.7% to 75.9% (p < 0.001). The median SLEDAI score decreased from 10 to 5 (p < 0.001), and the proportion of patients achieving low lupus disease activity state (LLDAS) increased from 11.11% to 16.67% (p < 0.001) by the 3-month evaluation. Notably, there were significant reductions in oral corticosteroid dosages, with a median decrease from 30 to 17.5 mg/day (p < 0.001) by 3 months, and the proportion of patients requiring >5 mg/day of steroids decreased from 88.89% at baseline to 79.07% at six months (p < 0.001). Compared to the conventional therapy group, the belimumab group experienced a significant reduction in median steroid dosage and increased the proportion of patients achieving remission or LLDAS. The incidence of treatment-emergent adverse events (TEAEs) was significantly lower in the belimumab group (29.6% vs 52.4%, p = 0.024). Conclusion: These findings support the potential of belimumab to improve renal and serological parameters, reduce disease activity, lessen corticosteroid dependence, and decrease the risk of TEAEs, demonstrating its safety and efficacy as an adjunct therapy in LN management.

Characteristics and outcomes of biopsy-proven lupus nephritis in the Eastern Cape province of South Africa.

OBJECTIVE: In Africa, the treatment outcomes of lupus nephritis (LN) are not well known. This is especially true in the current era where contemporary treatment options are more widely available. This retrospective study aimed to measure the outcomes of biopsy-proven LN treated at the Livingstone Tertiary Hospital (LTH) Renal Unit in Gqeberha (formerly Port Elizabeth), South Africa and to identify predictors of a poor outcome. METHODS: A retrospective cohort study of 131 patients with biopsy-proven LN who had a kidney biopsy between 01 January 2012 to 31 December 2021 as identified from the biopsy register. A sub-analysis of 107 patients with proliferative and/or membranous LN was performed. RESULTS: Mean age was 31.4 ± 12.7 years with a female predominance of 86.3%. At 6-month follow-up, 69.6% of patients had complete or partial response to treatment. This increased to 70.3% and 72.6% at 18 and 30 months, respectively. Twenty-seven patients were lost to follow-up, while 7 (5.3%) patients progressed to kidney failure (KF). There were 3 (2.3%) deaths. Predictors of poor response were an elevated baseline serum creatinine (OR = 2.53, 95% CI 0.99 - 6.52, p = .054), a decreased eGFR (OR = 2.92, 95% CI 0.94 - 9.09, p = .065) and an elevated blood pressure (OR = 6.06, 95% CI 1.11 - 33.33, p = .038) at the time of biopsy. Infections were the most common adverse event with 50 infections seen in 39 (29.8%) patients. Herpes viral infections were frequently noted (n = 12) accounting for 24.0% of all documented infections. CONCLUSION: Response rates were similar in this cohort when compared to other contemporary studies. Predictors of poor response were an elevated baseline serum creatinine, a decreased eGFR and an elevated blood pressure at time of the biopsy. Infections were the most common occurring adverse event, although the mortality rate remained low at 2.3%.

Attainment of EULAR/ERA-EDTA targets of therapy with current immunosuppressive regimens and adjustments in treatment: a multicentre, real-life observational study.

OBJECTIVE: To estimate real-life European Alliance of Associations for Rheumatology (EULAR)/European Renal Association (ERA)-European Dialysis and Transplantation Association (EDTA) response rates and predictors for no response in patients with lupus nephritis (LN) managed with conventional immunosuppressive therapies. METHODS: Ambidirectional cohort study of patients with new-onset LN (period 2014-to date). Response rates in the first year were calculated, and all treatment modifications were recorded. Univariate and multivariate regression analyses were performed to assess determinants of failure to respond at 12 months. RESULTS: 140 patients were included (81.4% women, median (IQR) age at LN diagnosis 38 (22) years). Among them, 32.1% presented with nephrotic range proteinuria, 28.6% with glomerular filtration rate <60 mL/min, 76.6% had proliferative and 19.7% class V LN. Initial treatment consisted of cyclophosphamide in 51.4% of patients (84.7% high-dose, 15.3% low-dose) and mycophenolate in 32.1%. 120 patients had available data at 12 months. EULAR/ERA-EDTA renal response rates at 3, 6 and 12 months were achieved by 72.6%, 78.5% % and 69.2% of patients, respectively. In multivariate analysis, increased Chronicity Index at baseline was associated with failure to achieve either complete or partial response at 12 months (OR 2.26, 95% CI 1.35 to 3.77). Notably, 20% of patients required treatment modifications due to suboptimal response during the first 12 months, with the addition of or switch to a different immunosuppressive drug in seven and nine patients, respectively. CONCLUSIONS: More than two-thirds of patients with LN attain EULAR/ERA-EDTA response rates by 12 months, but 20% require therapy modifications within this time period. Patients with increased chronicity in baseline biopsy, when combined with histological activity, are at higher risk for a lack of clinical response.

Apigenin ameliorates lupus nephritis by inhibiting SAT3 signaling in CD8+ T cells.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by widespread organ and tissue involvement, with lupus nephritis (LN) being one of its most severe complications. Dietary flavonoids, as for their anti-inflammatory and antioxidant properties, have shown therapeutic potential under various inflammatory conditions. Apigenin (AP) is one of the most studied phenolics and is found in many fruits, vegetables and herbs. This study aimed to investigate the therapeutic effects and underlying mechanisms of apigenin on LN. We evaluated the effects of apigenin on MRL/lpr mice, a well-established model for spontaneous LN. Apigenin treatment improved peripheral blood profiles, reduced serum inflammatory cytokines (IL-6, IFN-γ, IL-17, TGF-ß), lowered levels of autoantibodies (ANA, anti-dsDNA) and alleviated renal damage caused by autoantibodies and inflammatory cell infiltration. The results of immunohistochemistry and transcriptome analysis showed that AP could inhibit the infiltration of CD8+ cells in renal tissues. Single-cell sequencing public data from LN patients identified cytotoxic T lymphocytes (CTLs) as the primary CD8+ T cell subtype in the kidneys, with their differentiation regulated by STAT3. In this study, cell experiments demonstrated that AP can induce apoptosis in CD8+ T cells and reduce their recruitment of macrophages by inhibiting the STAT3/IL-17 signaling pathway. These findings highlight that a diet rich in dietary flavonoids, particularly apigenin, can offer therapeutic benefits for patients with SLE.

Biologicals for the treatment of lupus nephritis: a Bayesian network meta-regression analysis.

Background: Previous studies comparing the efficacy and safety of different treatment regimens for lupus nephritis are scarce. Moreover, confounding factors such as the duration of follow-up were hardly adjusted in those studies, potentially compromising the results and their extents to clinical settings. Objective: To rigorously investigate the efficacy and safety of biologics in patients with lupus nephritis using Bayesian network meta-regression analyses that adjust for the follow-up period, in order to provide more robust evidence for clinicians. Methods: Databases comprising PubMed, Embase, MedlinePlus, Cochrane Library, Google Scholars, and Scopus were retrieved for eligible articles from inception to February 29, 2024. The primary endpoint was the complete response rate, the secondary endpoint was the partial response rate, the tertiary endpoints were the adverse events, and infection-related adverse events. Napierian Logarithm of hazard ratio (lnHR) and the standard error of lnHR (selnHR) were generated for dichotomous variants by STATA 18.0 MP and then put into Rstudio 4.3.2 to conduct Bayesian network meta-analysis as well as network meta-regression analysis to yield hazard ratio (HR) as pairwise effect size. Results: Ten studies involving 2138 patients and 11 treatment regimens were ultimately included. In the original analysis, for the primary endpoint, compared to the control group, obinutuzumab (22.6 months), abatacept-30mg (20.5 months), abatacept-10mg (17.8 months), and belimumab (23.3 months) demonstrated significant superiority (HR ranged from 1.6 to 2.5), more ever, their significance regarding relative efficacy was correlated with follow up period, namely "time window" (shown in parentheses above). For the secondary endpoint, compared to the control group, obinutuzumab and abatacept-30mg showed conspicuous preponderance (HR ranged from 1.6 to 2.4), "time window" was also detected in abatacept-30mg (20.5 months), whereas obinutuzumab remained consistently obviously effective regardless of the follow-up period (shown in parentheses above). For the tertiary endpoint, there were no differences among active regimens and control. Conclusions: Considering the efficacy and safety and "time window" phenomenon, we recommend obinutuzumab as the preferred treatment for LN. Certainly, more rigorous head-to-head clinical trials are warranted to validate those findings.

Demethylzeylasteral ameliorates podocyte damage in murine lupus by inhibiting inflammation and enhancing autophagy.

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with multiorgan and tissue involvement. Lupus nephritis (LN), an inflammatory condition of the kidneys associated with SLE, represents a significant cause of morbidity and mortality in SLE patients. Current immunosuppressive therapies for LN have limited efficacy and can lead to significant side effects. Demethylzeylasteral (DML) has shown promise in the treatment of LN, but its precise mechanism of action remains unclear. PURPOSE: To assess the therapeutic effects and potential molecular mechanisms of DML in LN METHODS: The study evaluated the renal protective effects of DML in MRL/lpr mice through assessments of immune complex levels, renal function, and pathological changes. Network pharmacology and transcriptomics approaches were used to elucidate the underlying mechanisms. Molecular docking, biacore assay, monoclonal antibody blocking experiments, and in vitro studies were conducted to verify the mechanisms of action. RESULTS: DML treatment reduced levels of anti-Sm and anti-dsDNA IgG antibodies, as well as serum creatinine and blood urea nitrogen levels. DML also mitigated glomerular damage and fibrosis. Mechanistically, DML alleviated podocyte damage by suppressing inflammation and enhancing autophagy through inhibition of the IL-17A/JAK2-STAT3 pathways. Additionally, DML exhibited high binding affinity with IL17A, JAK2, and STAT3. CONCLUSION: These findings provide strong evidence for the beneficial effects of DML in LN, suggesting its potential as a novel therapeutic strategy for improving renal function in autoimmune kidney diseases.

Treatment adherence and quality of life in colombian patients with lupus nephritis.

BACKGROUND: As with many other chronic diseases, systemic lupus erythematosus (SLE) and lupus nephritis (LN) have significant impacts on the health-related quality of life (HRQoL). Medication non-adherence is a significant challenge in the management of SLE, with consistently up to 75% of patients being non-adherent with their SLE medications. There is a need to assess the patient's perspective using patient-reported outcomes (PROs) to better understand the current impact of LN on HRQoL and treatment adherence in our region. The aim of this study was to explore the relationship between HRQoL and treatment adherence in patients with LN from the Colombian Caribbean. METHODS: A cross-sectional study was conducted from June to December 2022, including patients with biopsy-proven LN. HRQoL and treatment adherence were assessed using the Lupus Quality of Life (LupusQoL) and the Compliance Questionnaire in Rheumatology 19 (CQR19) instruments, respectively. Patients were categorized as adherent or non-adherent based on medication intake (defined as >80% correct dosage). Principal component analysis (PCA) was employed to identify principal components between adherent and non-adherent patients. RESULTS: A total of 42 patients with LN were included. Of these, 38 (90%) were female, and the mean age was 31 ± 10 years. Proliferative class IV was the predominant histopathological profile (90%). Twenty-five (60%) patients were categorized as non-adherent. Across all LupusQoL domains, a comprehensive range of responses was observed. Pain, planning, and intimate relationships domains remained unaffected, while burden to others domain had the lowest score. Poorer planning score correlated with older age (r = -0.72; p < .05) and longer disease duration (r = -0.74; p < .05). SLEDAI-2 K correlated with the pain domain (r = -0.78; p < .05). Non-adherent patients exhibited significantly worse pain domain scores compared to adherent counterparts (p < .05). PCA showed strong interactions between planning and pain, as well as between physical health and body image domains. CONCLUSIONS: LupusQoL pain domain scores were significantly worse in non-adherent patients compared to adherent patients. Effective pain management could be a determinant in HRQoL and treatment adherence rates in our population.

Extrapolation of the Efficacy and Pharmacokinetics of Belimumab to Support its Use in Children with Lupus Nephritis.

BACKGROUND AND OBJECTIVE: Lupus nephritis (LN), a severe manifestation of systemic lupus erythematosus, has greater severity in children versus adults. Belimumab is approved for systemic lupus erythematosus treatment in patients aged ≥ 5 years, and for active LN in adults in the European Union, China, Japan and Latin America, and patients aged ≥ 5 years in the USA. Low prevalence of paediatric active LN makes conducting a clinical study within a reasonable period unfeasible. We describe a model-based extrapolation of belimumab efficacy and pharmacokinetics from adults to children with LN to support US Food and Drug Administration approval of intravenous belimumab 10 mg/kg (administered every 4 weeks after the loading dose) in children (aged 5-17 years) with active LN. METHODS: This concept assumed that disease progression, response to belimumab, exposure-response, and the target belimumab exposure for efficacy are similar across adult and paediatric systemic lupus erythematosus and LN, evaluated against the published literature for paediatric LN and belimumab systemic lupus erythematosus and LN clinical trial data in adults and children. A two-compartmental population pharmacokinetic model, previously developed for adults with LN, was used to extrapolate belimumab pharmacokinetics to children with LN. RESULTS: The model captured the dependence of time-varying proteinuria on belimumab clearance, and therefore exposure. Sufficient target exposures for efficacy were achieved in children with active LN. A small proportion of children aged 5-11 years are predicted to have exposures below adult levels but no impact to efficacy is expected. CONCLUSIONS: Our model demonstrated that intravenous belimumab 10 mg/kg every 4 weeks is appropriate for children aged 5-17 years with active LN.

Lupus nephritis is a serious illness of the kidneys that can develop in patients with systemic lupus erythematosus. Lupus nephritis can be especially serious in children. Belimumab is a medication often used to treat adults and children with systemic lupus erythematosus, and adults with lupus nephritis. As a result of our study, it is now also used to treat children with lupus nephritis in the USA.Belimumab was first tested in lupus nephritis clinical trials in adults, but not in children. This is because lupus nephritis is rare in children, and it would take too long to find enough patients for a trial. Instead, we used information from scientific articles and clinical trials in adults and children with lupus nephritis. As lupus nephritis affects adults and children similarly, we used a mathematical model to test if the belimumab dose used in adults could also treat lupus nephritis in children who are aged between 5 and 17 years.To test this, we assumed that adults and children react to the same dose of belimumab in a similar way. The dose we looked at was 10 mg of belimumab for every 1 kg of patient's body weight (10 mg/kg), which is given each month via the veins. Our model also looked at how belimumab moves through the body and how this illness affects kidneys. We found that the belimumab dose scheme we looked at (10 mg/kg/month) can be used to treat children with lupus nephritis.

Efficacy and safety of biologics, multitarget therapy, and standard therapy for lupus nephritis: a systematic review and network meta-analysis.

OBJECTIVE: This study aimed to compare the efficacy and safety of biologics, multitarget therapy, and standard therapy for the induction of lupus nephritis. METHODS: A systematic search of electronic databases (EMBASE, Web of Science, PubMed, Cochrane Library, and ClinicalTrials.gov) was conducted from inception to 30 August 2023. Our study included randomized controlled trials enrolling adult lupus nephritis patients treated with biologics or multitarget therapy, in comparison with standard therapy. The primary outcomes were the rates of complete renal remission (CRR) and serious adverse events (SAE). Stata 15.0 was used to conduct the network meta-analysis. RESULTS: Ten randomized controlled trials with a total of 1989 patients met the inclusion criteria. The network meta-analysis indicated that compared with standard therapy, multitarget therapy, obinutuzumab, belimumab, and voclosporin therapy demonstrated superior efficacy in achieving complete renal remission. Among these options, multitarget therapy had the greatest effect (OR = 2.78, 95% CI = 1.81-4.26). Regarding safety, it was observed that there were no significant statistical differences among the various treatment options. Cluster analysis revealed that both obinutuzumab and belimumab exhibited good efficacy and safety. CONCLUSIONS: belimumab and obinutuzumab stood out as promising treatments due to their good performance in terms of efficacy and safety. Multitarget therapy may be the most effective approach for treating lupus nephritis. However, since the study population consists exclusively of Asian patients, further research is needed to verify the efficacy of multitarget therapy in lupus nephritis patients of non-Asian descent.

Lupus Nephritis from Pathogenesis to New Therapies: An Update.

Lupus Nephritis (LN) still represents one of the most severe complications of Systemic Lupus Erythematosus (SLE) and a major risk factor for morbidity and mortality. However, over the last few years, several studies have paved the way for a deeper understanding of its pathogenetic mechanisms and more targeted treatments. This review aims to provide a comprehensive update on progress on several key aspects in this setting: pathogenetic mechanisms of LN, including new insight into the role of autoantibodies, complement, vitamin D deficiency, and interaction between infiltrating immune cells and kidney resident ones; the evolving role of renal biopsy and biomarkers, which may integrate information from renal histology; newly approved drugs such as voclosporin (VOC) and belimumab (BEL), allowing a more articulate strategy for induction therapy, and other promising phase III-immunosuppressive (IS) agents in the pipeline. Several adjunctive treatments aimed at reducing cardiovascular risk and progression of chronic renal damage, such as antiproteinuric agents, represent an important complement to IS therapy. Furthermore, non-pharmacological measures concerning general lifestyle and diet should also be adopted when managing LN. Integrating these therapeutic areas requires an effort towards a holistic and multidisciplinary approach. At the same time, the availability of an increasingly wider armamentarium may translate into improvements in patient's renal outcomes over the next decades.

Belimumab in early systemic lupus erythematosus: A propensity score matching analysis.

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.

[Kidney diseases: News from the KDIGO guidelines]. / Nierenkrankheiten: Neues aus den KDIGO-Leitlinien.

The KDIGO Update 2024 was supplemented by new "Clinical Practice Points", which were derived from the current evidence but are not necessarily comprehensively proven by prospective controlled studies. The most significant change in the Update 2024 for Lupus nephritis concerns the recommendations for induction therapy for lupus nephritis classes III and IV. The basis is still high-dose glucocorticoid treatment and the use of hydroxychloroquine. The 2 new developments in the 2024 Update concerning ANCA-associated nephritis are based on the studies on the use of the C5a receptor inhibitor Avacopan and the increasing data on induction protocols with reduced glucocorticoid dosage. Due to the inconsistency and variability of the conditions under which blood pressure measurements are carried out in practice, an international consensus statement was issued which defines 4 steps to achieve sufficient validity of the measurement results. CKD-MBD Controversies Conference 2023: The update for CKD-MBD, which was discussed in the Controversies Conference 2023, is in progress and has not been released yet. However, there were no serious contradictions between the 2023 data and the 2017 guidelines - the risk assessment regarding calcium-containing phosphate binders may have been put into perspective.

"Lupus Doesn't Have Me, I Have Lupus": Using Patient-Centered Interviews to Understand Medication Nonadherence.

BACKGROUND: Lupus nephritis (LN) is the most common cause of kidney injury in systemic lupus erythematosus and associated with higher morbidity and mortality. Low medication adherence correlates with adverse clinical outcomes. METHODS: In a large, integrated health system at Kaiser Permanente East Bay Area, the authors identified mycophenolate mofetil (MMF) prescriptions for LN and collected patient demographics, medication adherence, and copay data. They interviewed patients with low medication adherence rates to understand contributing factors, such as side effects, cost, refill processes, and laboratory draws. Adherence was defined as a proportion of days covered at > 80%. The proportion of days covered is the number of days covered by a medication divided by the number of days in a defined period. RESULTS: Between November 30, 2021, and November 30, 2022, the authors identified 36 patients with LN on MMF. Almost a third (11/36) of these patients were nonadherent to medication. More than half (7/11) of these patients agreed to be interviewed. They identified the following causes of medication nonadherence: forgetfulness (57%, or 4/7), incomplete laboratory work (28%, or 2/7), medication cost (14%, or 1/7), and intentionally missed doses (14%, or 1/7). No patients identified medication side effects as a cause. The median 30-day copay for MMF was $4.55, and 28% (2/7) of patients paid $0 for their medications. CONCLUSIONS: In the authors' integrated health system, 69% of their patients with LN on MMF were adherent to their medication regimen. Forgetfulness was a challenge for the nonadherent patients. Kaiser Permanente East Bay Area provides convenient refills and laboratory draws; this likely facilitates medication adherence.

[EULAR recommendations 2023 on the treatment of systemic lupus erythematosus -Implications for treatment in Germany]. / Die 2023 EULAR-Empfehlungen zur Behandlung des systemischen Lupus erythematodes ­ Implikationen für die Versorgung in Deutschland.

The 2023 update of the EULAR recommendations for the management of systemic lupus erythematosus (SLE) faced several tasks: the newly approved medications anifrolumab and voclosporin as well as the additional approval of belimumab for lupus nephritis had to be conceptionally fitted into the management of SLE. Novel data on hydroxychloroquine and glucocorticoids, additional results for the treat-to-target goals remission and low disease activity and experience with respect to vaccinations and infections had to be considered. Additionally, EULAR specified a slightly modified structure. The update was further developed with 5 overarching principles and 13 recommendations. An SLE activity score is required for each patient visit. All SLE patients should receive hydroxychloroquine at a target dose of 5 mg/kg body weight. Glucocorticoids should only be used if necessary and reduced to not more than 5 mg prednisone equivalent daily in the long-term or, even better, tapered off. If the target of remission or low disease activity is not reached, methotrexate, azathioprine, mycophenolate and/or belimumab or anifrolumab should be used. For lupus nephritis, Euro-Lupus cyclophosphamide or mycophenolate are options for induction therapy and mycophenolate or azathioprine for maintenance. In the case of severe nephritis, the addition of belimumab or a calcineurin inhibitor (voclosporin or tacrolimus) should be considered. It is important that treatment should be continued for at least 3 years. This review article describes the details of the new recommendations against the background of relevant studies in recent years and classifies them in the clinical context.

Type I interferon gene expression signature as a marker to predict response to cyclophosphamide based treatment in proliferative lupus nephritis.

OBJECTIVES: To assess the longitudinal effect of cyclophosphamide (CYC) treatment on type-I interferon (IFN) signature in proliferative lupus nephritis (LN) and its role in predicting treatment response. METHODS: Fifty-four biopsy proven proliferative LN patients scheduled to receive high-dose (HD) or low-dose (LD) CYC were recruited and followed up for six months. At six months, patients were classified as clinical responders (CR) or non-responders (NR) to treatment, using the EULAR/EDTA criteria. An IFN-gene based score (IGS) was developed from the mean log-transformed gene expression of MX1, OAS1, IFIT1, OASL, IFIT4, LY6E, IRF7 at baseline, three and six months. Longitudinal changes of IGS within and between groups were assessed and ΔIGS, which is the difference in IGS between baseline and three months was calculated. Independent predictors of non-response were identified and an ROC analysis was performed to evaluate their utility to predict NR. RESULTS: There was a dynamic change in IGS within the HD, LD, CR, and NR groups. Compared to baseline, there was a significant decrease in IGS at three months in HD and LD groups (HD group: 2.01 to 1.14, p = .001; LD group = 2.01 to 0.81, p < .001), followed by a significant increase from three to six months in LD group (LD: 0.81 to 1.51, p = .03; HD: 1.14 to 1.54, p = .300). A decrease in IGS from baseline to three months was seen in both CR (2.13 to 0.79, p < .001) and NR groups (1.83 to 1.27, p = .046), and a significant increase from three to six months was observed only in the CR group (CR: 0.79 to 1.57, p = .006; NR: 1.27 to 1.46, p = 1). ΔIGS (baseline to three months) was higher in CR compared to NR group (-1.339 vs -0.563, p = .017). ROC analysis showed that the model comprising of 0.81 fold decrease in IGS from baseline to three months, endocapillary hypercellularity and interstitial inflammation on renal histopathology predicted non-response with a sensitivity of 83.3% and specificity of 71.4%. CONCLUSION: In proliferative LN, treated with HD or LD-CYC, combined model comprising of decrease in IGS score by 0.81 fold from baseline to three months, along with important histopathological features such as endocapillary hypercellularity and interstitial inflammation had better predictive capability for non-response.

Dioscin attenuates lupus nephritis in NZB/W F1 mice by decreasing NF-κB activation and NLRP3 inflammasome.

INTRODUCTION: Dioscin, a natural steroid saponin, has anticancer, anti-inflammatory, anti-hyperlipidemic, and glycemic capabilities. This study focused on dioscin roles and its related mechanisms in experimental lupus nephritis. MATERIALS AND METHODS: Lupus-prone NZB/W F1 mice were intragastrically administered with dioscin, prednisone or vehicle, and kidney, urine and blood samples were harvested after the mice were sacrificed. Proteinuria, blood urea nitrogen (BUN), creatinine, anti-dsDNA, IL-1ß, and IL-18 levels in serum as well as IFN-γ, IL-6, IL-17 and TNF-α levels in kidney tissues were assessed. Renal histopathology was examined through hematoxylin-eosin staining. IgG and C3 expression in kidney was evaluated using immunofluorescence staining. The number of glomerular F4/80-positive cells and NLRP3-positive cells was determined by immunohistochemical staining. The protein expression was examined by western blotting. RESULTS: Dioscin alleviated lupus nephritis in NZB/W F1 mice. Dioscin declined serum anti-dsDNA level, prevented deposition of immune complexes in renal glomeruli, and inhibited the inflammatory response and infiltration of macrophages into mouse kidneys. Dioscin inhibited NF-κB and NLRP3 inflammasome in NZB/W F1 mice. CONCLUSIONS: Dioscin ameliorates lupus nephritis through inhibition of NLRP3 inflammasome and NF-κB signaling.

[Treatment of lupus nephritis]. / Prise en charge de la néphropathie lupique en 2023.

Lupus nephritis remains the most frequent severe complication of systemic lupus erythematosus, leading to chronic renal impairment in 20 to 25% of cases. Current treatment is based on the combined use of immunosuppressive treatment and targeted biotherapies to optimize the chances of promptly obtaining and maintaining a complete renal response over the long term. The author discusses these recent advances.

Title: Prise en charge de la néphropathie lupique en 2023. Abstract: La néphropathie lupique reste la complication sévère la plus fréquente du lupus érythémateux disséminé. Elle évolue vers l'insuffisance rénale chronique dans 20 à 25 % des cas. Son traitement moderne repose sur l'utilisation combinée d'un traitement immunosuppresseur et de biothérapies ciblées pour optimiser les chances d'obtenir rapidement et de maintenir au long cours une réponse rénale complète. L'auteur discute ces progrès récents.

Curcumin attenuates lupus nephritis by inhibiting neutrophil migration via PI3K/AKT/NF-κB signalling pathway.

OBJECTIVE: To investigate the role of curcumin in the treatment of lupus nephritis (LN) by inhibiting the migration of neutrophils and the underlying mechanism involved. METHODS: Two lupus mouse models, MRL/lpr mice and R848-treated mice, were treated with 50 mg/kg curcumin by intraperitoneal injection. H&E and Masson staining were used to estimate histopathological changes in the kidney. Immunofluorescence was used to assess the deposition of immune complexes. The expression of inflammatory factors was detected by enzyme-linked immunosorbent assay (ELISA) and real-time reverse transcription polymerase reaction (RT-PCR), and the protein expression was detected by western blotting. RESULTS: We revealed the remarkable potential of curcumin in improving inflammatory conditions in both MRL/lpr mice and R848-induced lupus mice. Curcumin effectively decelerates the progression of inflammation and diminishes the infiltration of neutrophils and their release of pivotal inflammatory factors, thereby reducing inflammation in renal tissues. Mechanistically, curcumin significantly inhibits the expression of p-PI3K, p-AKT and p-NF-κB, which are upregulated by interleukin-8 to induce neutrophil migration and renal inflammation, thereby reducing neutrophil migration and the release of inflammatory factors. CONCLUSION: Curcumin significantly inhibits the recruitment of neutrophils and the release of proinflammatory factors in the kidney by inhibiting the PI3K/AKT/NF-κB signalling pathway, providing new therapeutic targets and medication strategies for the treatment of LN.