Initiation of belimumab with higher daily prednisolone is effective for rapid glucocorticoid reduction: A 96-week retrospective study.

OBJECTIVES: For appropriate glucocorticoid (GC) reduction, we investigated the optimal strategy including baseline factors that could reduce GC more than 50% with 96 weeks of belimumab. METHODS: This is a retrospective cohort study of Kakogawa Central City hospital from 2019 to 2023. We identified SLE patients who were receiving 200 mg of belimumab weekly by subcutaneous injection for 96 weeks. The background at baseline, trends in clinical indicators, and factors involved in GC reduction were statistically analyzed. Finally, univariate and multivariate logistic analyses were carried out to identify baseline factors associated ≥50% GC reduction at 96 weeks. RESULTS: Forty-seven patients were enrolled, with a median daily prednisolone of 5 mg. Almost 90% of them received concomitant immunosuppressants and/or hydroxychloroquine. Serological indices, daily GC dose, and SLEDAI-2K scores showed significant improvement in 96 weeks. At baseline, a significant negative correlation has been shown between the daily dose of GC and the duration from onset or last flare, as well as C4 levels. At 96 weeks, GC reduction rate and SLEDAI-2K scores were negatively correlated with duration from onset or last flare to initiation of belimumab. Mycophenolate mofetil use was significantly frequent in patients with lupus nephritis (LN), which also correlated with the frequency of past flares. In addition, LN presence was associated with higher SLEDAI-2K scores at 96 weeks, and baseline SLEDAI-2K ≥10 was associated with significantly higher GC dose at 96 weeks. Univariate analysis of the factor contributing to achieving ≥50% GC reduction at 96 weeks has pointed shorter disease duration and higher daily GC dose at baseline as significant variables. Finally, we performed a multivariate analysis by combining above two items with age, which extracted the higher daily GC dose at baseline as a significant variable (OR (95% CI) 1.25 (1.00 to 1.56), p = .047). CONCLUSIONS: Our study showed that a delay in belimumab initiation led to higher SLEDAI-2K score and difficulty in achieving a 50% GC reduction at 96 weeks. Since GC-related adverse events increase with long-term administration of GC though with small daily doses, we proposed here that belimumab should be started in combination with higher daily prednisolone.

Rituximab as add-on therapy in patients with resistant lupus nephritis who have failed induction or maintenance therapy with other agents: A real-world experience from a single center in Mumbai.

BACKGROUND: Lupus nephritis (LN) is associated with poor outcomes and a significant risk of progression to end-stage renal disease (ESRD). Some patients with resistant LN do not respond adequately to current treatment options and need alternative strategies or therapies. OBJECTIVE: The objective is to evaluate the efficacy and safety of rituximab as a re-induction therapy (Re-RTX) followed by maintenance therapy for patients with resistant LN. METHODS: Twenty-four patients with resistant LN (failed initial induction therapy or severe relapse after remission) were analyzed. Re-RTX was co-administered with other immunosuppressants. The primary KDIGO criteria outcomes included renal response (complete and partial), disease progression, relapses, and infections. RESULTS: The median age was 28 years (IQR 24.5-42), and the female-to-male ratio was 11:1. All patients had active LN, and 91.3% had proliferative LN. Baseline creatinine was 1.075 mg% (IQR 0.7-1.38), and mean urine protein-to-creatinine ratio (UPCR) was 4.9 (IQR 2.8-6.65). Of the patients receiving RTX as re-induction therapy, 66.6% (16/24) had failed initial induction therapy with other immunosuppressants, whereas 33.3% (8/24) had severe relapse during maintenance therapy.Re-RTX had a favorable renal response at 6 months, with 91.7% of the patients responding (20.8% complete response and 70.8% partial response). At 12 months, 58.3% of the patients maintained a renal response (25% complete response and 33.3% partial response). Approximately one-third of patients relapsed within a year.Fourteen patients (58.3%) continued RTX maintenance therapy with two different treatment regimens. At 6 months, Regimen-1 (500 mg every 6 months) resulted in a partial response in 43% (3/7) and relapse in 57% (4/7) of patients. Regimen 2 (1 g dose per year) achieved a complete response in 28.5% (2/7) and a partial response in 71.5% (5/7) with no relapses at 6 months.At a median follow-up of 29 months, adverse renal outcomes were observed in 29.16% of the patients with progression to advanced chronic kidney disease (CKD) or end-stage renal disease (ESRD). The overall use of Re-RTX was considered safe, with a reported infection prevalence of 16%, which is comparable to the existing data. CONCLUSION: Re-RTX demonstrated efficacy and safety as an induction therapy for resistant LN. However, the response waned after 1 year, underscoring the need for optimized maintenance therapy.

Comparison of efficacy of continuous mycophenolate mofetil with sequential cyclophosphamide and tacrolimus as maintenance therapy for lupus nephritis.

OBJECTIVES: To evaluate the renal response to mycophenolate mofetil (MMF) as maintenance therapy for lupus nephritis (LN) in Japanese patients, we compared the efficacy of MMF and the sequential use of monthly intravenous cyclophosphamide (IVCY) followed by tacrolimus (TAC). METHODS: We examined 14 patients with LN who were treated with continuous MMF as induction and maintenance therapies (MMF group) and 10 patients with LN who received monthly IVCY as induction therapy followed by maintenance therapy with TAC (IVCY-TAC group). We assessed the therapeutic effects of each treatment regimen on renal manifestations and serological findings over a 36-month period after treatment initiation. RESULTS: Mean urine protein-to-creatinine ratios in the MMF and IVCY-TAC groups significantly decreased from 2.75 to 0.11 g/gCr and from 3.26 to 0.22 g/gCr, respectively. Significant improvements in serum immunological variables (serum complement C3 or C4 levels and the anti-double-stranded DNA antibody titer) and reductions in the SLE disease activity index and daily prednisolone dosages were observed in both groups during induction therapy and were maintained during maintenance therapy. Efficacy was similar between the MMF and IVCY-TAC groups. CONCLUSION: MMF has potential as an effective treatment for renal manifestations in Japanese patients throughout induction and maintenance therapies for LN, as an alternative to conventional IVCY-TAC therapy, and as a glucocorticoid-sparing agent.

Membranous lupus nephritis secondary to secukinumab therapy: A case report and literature review.

The interleukin (IL)-17 axis is involved in many inflammatory and autoimmune diseases. Secukinumab, an IL-17 inhibitor, has been approved for psoriasis treatment. There are accumulating cases of lupus erythematosus induced by IL-17 inhibition. Lupus nephritis after IL-17 inhibition has not been reported. We report the case of a 57-year-old man who developed membranous lupus nephritis after secukinumab treatment for psoriasis. Anti-SSA and PM-Scl antibodies were positive. dsDNA, anti-Smith, and anti-histone antibodies were negative, and serum complement was low. Secukinumab was discontinued, while tacrolimus was initiated, subsequently switched to cyclosporin, belimumab, glucocorticosteroid, and hydroxychloroquine with a good response. The relationship between lupus erythematosus and IL-17 inhibition requires further research.

Repeat kidney biopsy findings of lupus nephritis patients in clinical remission treated with Mycophenolate associated with Belimumab or Mycophenolate plus standard of care therapy. A "post-hoc" analysis of participants in the BLISS-LN and open label extension study belonging to a single center.

BACKGROUND: Lupus nephritis affects 40 to 70% of Systemic Lupus Erythematous(SLE) patients increasing their morbi-mortality; therefore, successful treatments are required to improve outcomes. RESEARCH DESIGN AND STUDY SAMPLE: In this paper 20 patients who participated in the BLISS LN trial at a single center (OMI) in Argentina were studied. All the patients continued Mycophenolate (MMF) treatment when the trial was finished and until a second biopsy was performed to determine the withdrawal of the immunosuppression according to the achieved clinical and histological response. Ten patients treated with MMF + Placebo versus 10 receiving MMF + Belimumab, were compared evaluating the complete clinical (CCR) and complete histological response (CHR) and the flares in each group. RESULTS: All the patients in the Belimumab group showed a CCR and 7 in the Placebo one; CHR was found in 9 and 5 patients of the Belimumab and Placebo group, respectively. None of the patients in the Belimumab group flared meanwhile two of the Placebo one did it. CONCLUSIONS: Although the number of patients is insufficient to be able to draw unquestionable conclusions, adding Belimumab to the standard of care treatment with MMF would seem to increase the possibility of achieving a CCR, CHR, and a lower rate of relapses during treatment and long follow-up.

Hydroxychloroquine in children with proliferative lupus nephritis: a randomized clinical trial.

Hydroxychloroquine (HCQ) is an antimalarial agent used to treat mucocutaneous, musculoskeletal, constitutional manifestations of systemic lupus erythematosus (SLE). This study assessed the efficacy and side effects of HCQ in children with proliferative lupus nephritis (LN). This double-blind, randomized, placebo-controlled trial study was conducted on 60 children with proliferative LN classes III and IV treated with steroids and a mycophenolate (MMF) regimen. Patients were categorized into two groups, the HCQ group (n = 30) and the placebo group (n = 30). They were evaluated initially at 6- and a 12-month follow-up by mucocutaneous, ophthalmological examination, and investigations (BUN, creatinine, 24 h proteinuria, triglycerides (TG), cholesterol, Antids-DNA, C3, C4). Disease activity was assessed using the SLE disease activity index (SLEDAI-2 k). After 12 months, TG, cholesterol, 24 h proteinuria, Antids-DNA, and SLEDAI score were significantly decreased in the HCQ group (P: 0.002, 0.012, 0.031, 0.001, respectively). After 12 months, the cumulative probabilities of developing primary end-points (LN partial and complete remission) were 40% and 60% in the HCQ group versus 53.3% and 36.7% in the placebo group (P: 0.002). After 12 months, the HCQ group experienced mucocutaneous alopecia (3.3%), hyperpigmentation (10%), and ophthalmological mild retinal changes (6.7%), but they did not differ significantly from the placebo group.  Cunclusion: HCQ improved the disease and LN activity in children with proliferative LN, with documented skin hyperpigmentation and mild retinal changes following HCQ use in a few cases. This study was registered on http://www. CLINICALTRIALS: gov/ with trial registration number (TRN): NCT03687905, September 2018 "retrospectively registered." WHAT IS KNOWN: • Hydroxychloroquine (HCQ) is documented as an adjunctive treatment in children with systemic lupus erythematosus (c-SLE) LN with efficacy in improving lupus musculoskeletal and mucocutaneous manifestations. • Due to the paucity of studies, its effects and side effects in children with LN remain unclear. WHAT IS NEW: • This pilot randomized clinical trial assessed the efficacy and adverse effects of HCQ in children with proliferative LN. • HCQ had numerous advantages for LN, including rapid and sustained remission, antilipidemic effect, and rapid improvement of kidney functions.

Comparative Efficacy and Safety of Biological Agents in the Treatment of Lupus Nephritis: A Network Meta-Analysis.

BACKGROUND: To date, no studies have described randomized controlled trials (RCTs) evaluating the effectiveness and safety of various biological agents used in induction therapy for lupus nephritis. OBJECTIVES: We designed this study to assess the relative efficacy and safety of some of these biological agents in patients with lupus nephritis. METHOD: We collected data from RCTs that examined the efficacy and safety of any biological agents for lupus nephritis and then used these data to complete a Bayesian network meta-analysis to combine the direct and indirect evidence from these studies. RESULTS: We identified nine RCTs evaluating rituximab, abatacept, belimumab, anifrolumab, obinutuzumab, ocrelizumab, and low-dose interleukin-2 (IL-2) across 1,480 patients. Low-dose IL-2, obinutuzumab, rituximab, and belimumab achieved complete remission in a significant proportion of respondents when compared with that in the control. Ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that low-dose IL-2 had the highest probability of achieving complete remission, followed by obinutuzumab, rituximab, belimumab, anifrolumab, abatacept, ocrelizumab, and the control. The risk of serious adverse events (SAE) tended to be lower for low-dose IL-2, rituximab, belimumab, and obinutuzumab than for the control. SUCRA-based ranking indicated that IL-2 had the highest probability of being safe, followed by rituximab, belimumab, obinutuzumab, control, anifrolumab, abatacept, and ocrelizumab. CONCLUSIONS: Low-dose IL-2 was the most effective induction treatment for patients with lupus nephritis and had the lowest potential for SAE. Higher complete remission rates and a more favorable safety profile suggest that low-dose IL-2, obinutuzumab, rituximab, and belimumab may be superior to the current control as treatments for lupus nephritis.

[Efficacy and safety of half-dose rituximab in the treatment of 23 cases with lupus nephritis].

The study aimed to analyze the efficacy and safety of rituximab in the treatment of 23 cases of lupus nephritis and explore the prospect of half-dose rituximab in lupus nephritis treatment. Twenty-three patients with lupus nephritis hospitalized in the Department of Rheumatology and Immunology at the First Medical Center of the PLA General Hospital from May 2013 to December 2021 were selected. Eighteen patients received rituximab 375 mg/m2 on the first and 14th days, 5 patients received 500 mg of rituximab on the first and 14th days, and rituximab was used as needed 6 months later. Methylprednisolone (80-120 mg) was given together with rituximab. Afterward, 1 mg/kg prednisone was used for 4 weeks, which was progressively tapered to maintenance doses or discontinued. B lymphocyte level, renal function, 24-h urine protein level, and systemic lupus erythematosus (SLE) disease activity index 2000 (SLEDAI2K) score before and after treatment were recorded. The efficacy and adverse reactions were analyzed. The results showed that 11 patients suffered from renal insufficiency [creatinine (162.7±58.6) µmol/L ] at baseline, while the creatinine level of 9 patients returned to normal 12 months after the treatment [ (66.3±10.1)µmol/L ]. Normal renal function of the other 12 patients was maintained during treatment. After 12 months, the 24-h urine protein level decreased from 4.00 (2.00,6.80) g in the baseline period to 0.10 (0.08,0.40) g. SLEDAI2K score decreased from 22 (18,26) in the baseline period to 3 (0,6) 12 months after the treatment. The B lymphocyte level reached 0.00 (0.00,0.01)% at 3 months. Of 23 patients, 13 patients achieved complete remission, and 7 patients achieved partial remission after 6 months of rituximab treatment. Five patients experienced adverse reactions related to rituximab, including 1 case of transfusion reaction, 1 case of perioral herpes with pulmonary infection, and 3 cases of decreased IgG levels. Therefore, rituximab regimen used in this study can be an effective treatment strategy for lupus nephritis.

A pharmacoeconomic study comparing the use of mycophenolate mofetil or cyclophosphamide as induction therapy in lupus nephritis patients in Egypt.

INTRODUCTION/OBJECTIVES: Lupus nephritis (LN) is a major and serious complication of systemic lupus erythematosus (SLE) and is associated with morbidity and mortality. The difference in drug cost between mycophenolate mofetil (MMF) and cyclophosphamide (CYC) inducing regimens becomes a relevant and realistic issue, especially in developing countries. Thus, this study aims to estimate and compare the costs and outcomes of CYC and MMF for better allocation of resources to reduce the burden on the Egyptian healthcare system. METHODS: A prospective, parallel observational study was conducted at Kasr Al-Aini Hospital between 2018 and 2020. One hundred and twenty-two LN patients were followed up monthly during the study period. Remission and maintenance of renal remission were assessed at 6 and 12 months from the start of therapy. Total direct medical costs associated with both regimens were examined. We applied the cost-minimization analysis method from governmental perspective. Besides, a prospective evaluation of reported changes in health-related quality of life using SF-36 was included in our study. RESULTS: There was no statistically significant difference in treatment response at 6 and 12 months (RR 0.6 [0.26;1.43] and 0.8 [0.27;2.33]), respectively, as well as the incidence of infection episodes between MMF and CYC group (71.4% versus 70.45%, p > 0.05). The average direct medical expenditures per patient in the MMF group were approximately one and half times more than the CYC group (2339.69 $ versus 1329.03 $, p <0.001). CONCLUSION: The CYC arm was associated with lower costs than the MMF arm, with equally effective outcomes indicating that CYC is an attractive treatment option.

Cost-effectiveness of cyclophosphamide and non-cyclophosphamide in the induction therapy of Malaysian lupus nephritis patients.

BACKGROUND: There is a paradigm shift in the induction therapy for proliferative lupus nephritis (LN). Apart from cyclophosphamide (CYC), mycophenolate mofetil and calcineurin inhibitors have emerged as an alternative option of treatment. OBJECTIVE: We aimed to compare the cost-effectiveness analysis (CEA) per year, adverse events and renal damage at 24 months between CYC and non-CYC agents (calcineurin inhibitors or mycophenolate) as induction treatment among proliferative lupus nephritis (LN) patients. METHODS: This was a retrospective and non-controlled study involving biopsy-proven proliferative LN patients (class III or IV with or without V) in the clinic registry from 2017 to 2019. Their medical records were reviewed to determine the date and type of induction, treatment effectiveness, adverse events and renal damage at 24 months. The total cost of treatment included capital cost (building, furniture and equipment) and recurrent cost (emolument, supply/drug, lab investigations, administrative cost and utilities). Treatment effectiveness was defined as renal remission (partial or complete) at 6 months without relapse up to 24 months. The cost-effectiveness analysis (CEA) was expressed as cost per remission per year in Malaysian Ringgit (MYR). RESULTS: There were a total of 95 inductions with CYC and 27 with non-CYC in 94 LN patients. There was no significant difference in the total mean cost per patient/year between CYC (MYR 18460.26 ± 6500.76) compared to non-CYC (MYR 19302.10 ± 6778.22), p = 0.569. The CEA for CYC was MYR 20,632.06 (GBP 3,538.78) while non-CYC was MYR 20,846.27 (GBP 3,575.52) and mean difference MYR 214.21 (GBP 37.44). There was significantly higher capital cost, consumables, utility, maintenance, administration (p < 0.001) and lab investigations (p = 0.046) in the CYC arm. There was a trend of a higher infection requiring outpatient antibiotic treatment in CYC group (p = 0.05), but similar renal damage outcome with the non-CYC group.Conclusion: For treatment of proliferative LN, there was no significant difference in the CEA and renal damage between CYC and non-CYC induction treatment. There was a trend of a higher rate of infections in the CYC group. Hence, the decision to treat patient with CYC or MMF should be tailored to individual patients, by considering the risk of infection in a particular patient.

Clinical pharmacology considerations for the approval of belimumab for the treatment of adult patients with active lupus nephritis: A regulatory perspective.

On 16 December 2020, FDA approved Benlysta® (belimumab) for both the intravenous (IV) and subcutaneous (SC) administration routes for the treatment of adult patients with active lupus nephritis (LN) who are receiving standard therapy. This approval represents the first FDA approved treatment of patients with active LN.The approved IV dosing regimen (10 mg/kg dose Q2W for three doses, then 10 mg/kg Q4W thereafter) was based on a randomized double-blind placebo controlled clinical trial in adult patients with LN. For the approval of the SC dosing regimen (400 mg dose QW for four doses, then 200 mg QW thereafter), efficacy was supported solely by pharmacokinetics (PK) modeling and simulation which estimated a matched steady state average concentration and higher trough concentrations for the SC administration route, for bridging to the efficacy of IV belimumab in adults with LN. The safety and immunogenicity profile of the SC administration route has been assessed in the SLE studies.In a population PK analysis, higher proteinuria was associated with greater belimumab clearance and lower belimumab exposure. In an exposure response analysis, the efficacy of belimumab as evaluated by renal response was mainly driven by patients with lower proteinuria at baseline regardless of other baseline characteristics (e.g. baseline renal function, renal biopsy classification), induction therapies, or belimumab exposure levels (within 10 mg/kg dosing regimen), etc. However, post hoc analyses showed that belimumab had activity in LN patients with higher proteinuria at baseline. There is no adequate information to suggest that a higher dose would provide additional benefit for patients with lower exposure (e.g. higher proteinuria).

Multitarget therapy versus monotherapy as induction treatment for lupus nephritis: A meta-analysis of randomized controlled trials.

AIM: The safety of multitarget treatments is of concern. This study aimed to evaluate the effectiveness and safety of multitarget therapy as an induction treatment for lupus nephritis in comparison with monotherapy. METHODS: This study included randomized controlled trials (RCTs) that evaluated the effectiveness and safety of multitarget therapies, such as voclosporin+mycophenolate mofetil (MMF), tacrolimus+MMF, or belimumab+standard of care in comparison with MMF or cyclophosphamide (CYC) monotherapy for induction treatment of lupus nephritis. We performed a meta-analysis of the efficacy and safety of multitarget therapy as an induction treatment for lupus nephritis in comparison with monotherapy. RESULTS: Six RCTs, including 1,437 participants, met the inclusion criteria. The complete remission rate was significantly higher in the multitarget therapy group than in the monotherapy group (odds ratio, 2.155; 95% CI, 1.695-2.739; p < 0.001). Subgroup analysis revealed that the complete remission rate was significantly higher in both tacrolimus+MMF and voclosporin+MMF groups as well as the belimumab+standard of care (SOC) than in the monotherapy or SOC group. The incidence of adverse events did not differ between the multitarget therapy and monotherapy groups. However, cases of infection and pneumonia were numerically higher in the multitarget therapy group than in the monotherapy group. In addition, the incidence of menstrual disorder was significantly lower in the tacrolimus+MMF group than in the CYC group, whereas that of new-onset hypertension was considerably higher in the tacrolimus+MMF group than in the CYC group. CONCLUSIONS: Multitarget therapy showed a higher complete remission rate than monotherapy; however, cases of infection and pneumonia were numerically more elevated in the multitarget therapy group than in the monotherapy group.

Efficacy and safety of belimumab in systemic lupus erythematosus patients with severe lupus nephritis requiring renal replacement therapy.

BACKGROUND: Systemic lupus erythematosus is a chronic inflammatory autoimmune disease that has various manifestations. Lupus nephritis is a common and severe presentation, which results in increased morbidity and mortality. Belimumab added on standard therapy has been proved to induce disease remission and improve renal parameters. However, the use of belimumab has not been explored in patients requiring dialysis treatment. METHODS: Seven patients diagnosed as SLE with renal involvement requiring dialysis, who received belimumab in addition to steroids or immunosuppressants were identified. Clinical and biological data were extracted from medical records and laboratory databases. Ten mg/kg belimumab was applied on day 1, 15, 29, and every 28 days thereafter for a total of 8 dose. Renal parameters including urine output and serum creatinine level, immunologic index including anti-ds-DNA antibody titer and complement level, and disease activity were documented to reveal the response to belimumab. RESULTS: After belimumab therapy, all the 7 patients receiving dialysis therapy showed immunologic improvement. Disease activity significantly declined from 16.5 to 5.33 using SLEDAI-2K score. Apart from patient 7 on maintenance dialysis, 5 of 6 patients had increased urine output and were out of dialysis treatment. Patient 5 and 6 showed significant decrease in serum creatinine level. Only one pulmonary infection was documented. CONCLUSIONS: Belimumab added to steroids or immunosuppressive agents was able to improve renal and immunologic parameters and decrease disease activity of SLE patients receiving dialysis treatment. The safety issue is promising with no severe adverse effect recorded. Further large, controlled, randomized clinical trials are required to confirm the results.

Comparative Efficacy and Safety of Tacrolimus, Cyclosporin A, Mycophenolate Mofetil, Cyclophosphamide, and Corticosteroids as Induction Therapy for Membranous Lupus Nephritis: A Network Meta-Analysis.

BACKGROUND: There were limited data on randomized controlled trials (RCTs) evaluating the effectiveness and safety of tacrolimus (TAC), cyclosporin A (CSA), mycophenolate mofetil (MMF), cyclophosphamide (CYC), and corticosteroids as induction agents in membranous lupus nephritis, and they were inconclusive. OBJECTIVES: This study aimed to assess the relative efficacy and safety TAC, CSA, MMF, CYC, and corticosteroids as induction therapy for membranous lupus nephritis. METHOD: RCTs examining the efficacy and safety of TAC, CSA, MMF, CYC, and corticosteroids as induction therapy in patients with membranous lupus nephritis were included. We performed a Bayesian random-effects network meta-analysis to combine direct and indirect evidence from the RCTs. RESULTS: Five RCTs comprising 126 patients met the inclusion criteria. TAC and CSA showed a trend toward a higher overall response rate (complete remission plus partial remission) than MMF and CYC. Similarly, MMF and CYC showed a trend toward a higher overall response than corticosteroids. Ranking probability based on the surface under the cumulative ranking curve indicated that TAC had the highest probability of being the best treatment for achieving the overall response, followed by CSA, MMF, CYC, and corticosteroids. In terms of safety, corticosteroids showed the highest probability of decreasing the risk of infections, followed by CSA, CYC, MMF, and TAC. CONCLUSIONS: TAC and CSA were the most efficacious induction treatments for patients with membranous lupus nephritis, and corticosteroids had the highest probability of decreasing the risk of infections.

First-line Combination Strategy Provides Favorable 5-year Outcomes for Patients with Lupus Nephritis: A Single-center Observational Study.

This observational study aimed to clarify the long-term results of the combination of mizoribine (MZB), tacrolimus (TAC) and prednisolone as first-line therapy for lupus nephritis (LN). This was our institution's standard therapy between 2009 and 2015, when we saw 36 patients with LN. When a patient thus treated achieved SLEDAI remission (= 0) and/or the prednisolone dose could be tapered to 5 mg/day, either MZB or TAC was stopped, and the other was continued for maintenance therapy. If treatment failure or relapse occurred, second-line therapy was introduced. At years 1 and 5, overall complete renal response and SLEDAI remission were 94% and 88%, and 50% and 62%, respectively. Excluding 2 cases lost to follow-up, medications after 5 years were as follows: 20 (59%) were stable on 1 drug (MZB or TAC), 11 (32%) required continuation of both drugs (MZB + TAC), and 3 (9%) required second-line therapy. The 5-year retention rate was 91% (non-secondline), with 0% of relapse in this group. Our first-line combination strategy showed high remission rates in the induction phase, and subsequent maintenance therapy demonstrated good outcomes for up to 5 years. Research that fine-tunes the order of therapeutic agents and institutes appropriate treatment goals may further improve long-term outcomes for patients with LN.

"Protenuria in SLE: Is it always lupus?"

Proteinuria is one of the most typical manifestations of kidney involvement in Systemic Lupus Erythematosus (SLE). We report the case of a 23-year-old woman with a 6-year-long history of SLE presenting with proteinuria after a three-year remission on hydroxychloroquine. Kidney histological examination showed alterations inconsistent with lupus nephritis and suggestive of hydroxychloroquine toxicity or Fabry disease. The latter was confirmed by genetic assay.

Acute effects of air pollution on lupus nephritis in patients with systemic lupus erythematosus: A multicenter panel study in China.

Air pollution may trigger systemic lupus erythematosus (SLE). However, few studies have investigated the associations between air pollution and complications of SLE, such as lupus nephritis (LN). In this study, multicenter longitudinal data from 13 hospitals in China, including 8552 SLE patients with 24,762 visits, were used. Based on the generalized estimating equation (GEE) model, we assessed the associations of LN occurrence with short-term exposures to different air pollutants including particulate matter with an aerodynamic diameter < 2.5 µm (PM2.5), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3). We identified 2672 LN patients, and about half of them were from east China. Our results based on the entire data set showed that PM2.5 and NO2 were risk factors for LN within one month after exposure, with odds ratio of 1.16 (95% confidence interval (CI), 1.08-1.19) at lag 18 day and 1.19 (95% CI, 1.12-1.26) at lag 16 day relative to an interquartile range (IQR) increase in PM2.5 and NO2, respectively. This positive association between LN and NO2 was also observed for south, west, and east China. In addition, we found that the short term exposure to CO and O3 was not generally associated with LN. Finally, the negative associations of LN with SO2 were found for the entire region and east China. Our results implied that SLE patients may gain the health benefits of air quality improvement in China. Our work also provided evidence that short-term variations in air pollution may trigger LN, and further studies are needed to confirm these findings and the potential pathogenic mechanisms should be explored.

Expression of XBP1s in B lymphocytes is critical for pristane-induced lupus nephritis in mice.

B lymphocyte hyperactivity plays a pathogenic role in systemic lupus erythematosus (SLE), and spliced X box-binding protein 1 (XBP1s) has been implicated in B cell maturation and differentiation. We hypothesized that blockade of the XBP1s pathway inhibits the B cell hyperactivity underlying SLE and lupus nephritis (LN) development. In the present study, we systematically evaluated the changes in B cell activation induced by the Xbp1 splicing inhibitor STF083010 in a pristane-induced lupus mouse model. The lupus mouse model was successfully established, as indicated by the presence of LN with markedly increased urine protein levels, renal deposition of Ig, and mesangial cell proliferation. In lupus mice, B cell hyperactivity was confirmed by increased CD40 and B cell-activating factor levels. B cell activation and plasma cell overproduction were determined by increases in CD40-positive and CD138-positive cells in the spleens of lupus mice by flow cytometry and further confirmed by CD45R and Ig light chain staining in the splenic tissues of lupus mice. mRNA and protein expression of XBP1s in B cells was assessed by real-time PCR, Western blot analysis, and immunofluorescence analysis and was increased in lupus mice. In addition, almost all changes were reversed by STF083010 treatment. However, the expression of XBP1s in the kidneys did not change when mice were exposed to pristane and STF083010. Taken together, these findings suggest that expression of XBP1s in B cells plays key roles in SLE and LN development. Blockade of the XBP1s pathway may be a potential strategy for SLE and LN treatment.

Lupus nephritis in a transgender woman on cross-sex hormone therapy: a case for the role of oestrogen in systemic lupus erythematosus.

We present the case of a 22-year-old African American transgender women (male to female), who was admitted for fatigue, abdominal pain and lower extremity edema and was diagnosed with systemic lupus erythematosus (SLE) and lupus nephritis. Treatment with high-dose steroids and mycophenolate mofetil helped resolve her symptoms. She has remained off oestrogen therapy since admission and has not experienced any major complications. It is important to consider therapy outcomes in this specific patient population. A review of four other cases of transgender women on cross-sex hormone therapy who were diagnosed with lupus is also presented.

Vasoactive intestinal peptide ameliorates renal injury in a pristane-induced lupus mouse model by modulating Th17/Treg balance.

BACKGROUND: Lupus nephritis (LN) is an inflammation of the kidneys and is a major cause of mortality in systemic lupus erythaematosus (SLE) patients. In addition, Th17/Treg balance is one of the most important factors that can promote the development of LN. It has been reported that vasoactive intestinal peptide (VIP) is associated with the downregulation of both inflammatory and autoimmune diseases through regulating T lymphocyte balance. Therefore, the aim of this study was to determine the role of VIP in modulating Th17/Treg balance in LN. METHODS: LN was induced in BALB/c female mice by injection pristane. After 3 months, mice were randomly divided into four groups: control, VIP + control, LN and VIP + LN. Autoantibody levels were tested by ELISA. The distribution of Th17/Treg cells in vivo and in vitro was detected by FC. Renal tissues were examined by PASM and DIF for pathology and Foxp3+CD3+. The mRNA and protein expression levels of pro- and anti-inflammatory cytokines were detected by qRT-PCR and western blotting. RESULTS: VIP can improve renal injury by regulating Th17/Treg imbalance in LN mice. Proteinuria, renal function defects and autoantibodies were significantly decreased, and Th17/Treg cell balance was restored in VIP compared with LN mice. In addition, VIP improved renal lesions by promoting the expression of Foxp3+CD3+ in renal tissue. Furthermore, VIP downregulated the mRNA and protein expression of IL-17, IL-6 and upregulated Foxp3, IL-10 expression. CONCLUSIONS: VIP reduced LN proteinuria and renal function defects and restored the Th17/Treg cell balance. Furthermore, VIP also downregulated autoantibody and inflammatory cytokine expression and upregulated Foxp3 and IL-10 expression.