Induction Treatment Of Lupus Nephritis Research Articles

Induction treatment for lupus nephritis at a high-complexity hospital in Chile.

Systemic lupus erythematosus (SLE) causes kidney compromise in up to 40% of patients, contributing significantly to morbidity. Lupus nephritis (LN), an early onset manifestation in most patients, is histologically classified into six types, with types III, IV, and V requiring treatment with induction therapies, usually glucocorticoids with mycophenolate mofetil (MMF) or intravenous cyclophosphamide (IVC). However, up to 60% of patients fail to achieve complete remission, and 27%-66% have subsequent flares. There is scarce literature on the superiority of IVC or MMF in the Latin population. A retrospective cohort study of 72 LN patients at a high-complexity hospital in Chile between 2016 and 2021 was conducted. Demographics, urine studies, creatinine levels, complement levels, antibody profiles, biopsy results, and response to treatment were analysed. The median age of the cohort was 29years, with women representing 90% of patients. At diagnosis, 87.5% of the patients presented with proteinuria, 55% had haematuria, and 49% had acute kidney injury. The most common LN type was type IV. For induction therapy, half of the patients were treated with IVC, and the other half with MMF. The response to treatment did not differ significantly between the two. This is one of the few studies to focus on the Latin American population, specifically Chile. These results are consistent with the current understanding of LN treatment. Despite its limitations, this study provides valuable insights into the treatment effectiveness of IVC and MMF in this population. This study did not find significant differences in the clinical response to IVC or MMF at 6months. Future prospective studies are required to determine the optimal induction therapy for LN, especially in Latin populations.

Risk Assessment of Cyclophosphamide and Mycophenolate Mofetil after Induction Treatment of Lupus Nephritis: A Single Center Quasi-Experimental Study

Background: The comparative safety of immunosuppressive drugs such as cyclophosphamide and mycophenolate mofetil for patients with lupus nephritis remains controversial. The study aimed to investigate the specific side effects of cyclophosphamide and mycophenolate mofetil in lupus nephritis patient after induction treatment.
 Materials and methods: It was a quasi-experimental study performed in the Department of Nephrology of Chittagong Medical College Hospital. A total of 100 patients of lupus nephritis who fulfilled the designated criteria were enrolled in this study by non-probability voluntary sampling method. The treatment was given on patient’s choice. After screening and treatment initiation, patients were assessed at 12 and 24 weeks. All the data were compiled in a structured case record form.
 Results: In the present study 48 patients (53.3%) in mycophenolate mofetil group and 42 patients (46.7%) in intravenous cyclophosphamide group completed 24 weeks of induction treatment of lupus nephritis. Infections were common in both treatment groups but significantly higher with intravenous cyclophosphamide group ((33.3% vs. 8.3%). Upper gastrointestinal syndrome occurred with 20(41%) patients in mycophenolate mofetil group and 7(16.7%) patients in intravenous cyclophosphamide group (RR=5.8333). Regarding other adverse effect, 10 patients of intravenous cyclophosphamide and two patients of mycophenolate mofetil group had amenorrhea (23.8% vs.4.2%). Alopecia (11.9%) was seen only by intravenous cyclophosphamide group ((RR=0.0798).
 Conclusion: Induction therapy with Mycophenolate mofetil was superior to intravenous cyclophosphamide in lupus nephritis in this study. Mycophenolate mofetil appeared to be better tolerated than cyclophosphamide.
 Chatt Maa Shi Hosp Med Coll J; Vol.22 (1); January 2023; Page 28-32

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

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. 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. 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. 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.

Belimumab: A BAFF-specific Inhibitor for the Treatment of Systemic Lupus Erythematosus and Lupus Nephritis

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that affects multiple organs. In particular, the presence of renal involvement, known as lupus nephritis, is a major determinant of prognosis. Conventional treatments for SLE include hydroxychloroquine, glucocorticoid and immunosuppressive agents. However, the use of such non-specific drugs increases the risk of side effects, such as infections. Soluble B-cell-activating factor (BAFF), belonging to the tumour necrosis factor family, is produced by dendritic cells and induces class switching of B cells and differentiation into antibody-producing cells. International phase III studies demonstrated the efficacy and safety of belimumab (a monoclonal antibody against soluble BAFF) not only in patients with SLE, but also in those with active lupus nephritis. There were no significant differences between the belimumab and placebo groups in the incidence of adverse events, including serious events and events necessitating drug cessation. Thus, belimumab could become an alternative induction treatment for lupus nephritis. This article describes the pathogenesis of SLE and lupus nephritis, and reviews the results of recent phase III trials of belimumab and its promising role for the treatment of patients.

Controversies in Systemic Lupus Erythematosus: Are We Treating Our Patients Adequately?

Systemic lupus erythematosus (SLE) is characterized by great clinical heterogeneity. The objectives of its management are to make a timely diagnosis and to initiate treatment as promptly as possible so organ damage can be avoided while at the same time exposure to potentially toxic drugs is minimized so that its overall course and outcome improve. In reviewing the current literature, it became quite clear that there are specific topics in which controversies do exist. These include how to treat patients with incomplete lupus erythematosus, the real possibility of abandoning altogether the use of oral glucocorticoids, and the pros and cons of the use of cyclophosphamide and mycophenolate mofetil for the induction treatment of lupus nephritis. Herein we discuss different points of view regarding these still unresolved issues; these comments represent a debate that took place during the PANLAR Virtual Congress (Pan American League of Associations for Rheumatology) and that was organized by the PANLAR Lupus study group, GLADEL (Grupo Latino Americano De Estudio del Lupus) on September 19, 2020.

Anetwork meta-analysis of randomized controlled trials comparing the effectiveness and safety of voclosporin or tacrolimus plus mycophenolate mofetil as induction treatment for lupus nephritis.

This study aimed to compare the effectiveness and safety of voclosporin + mycophenolate mofetil (MMF), tacrolimus + MMF, and monotherapy with MMF or cyclophosphamide as induction treatment for lupus nephritis. The study included randomized controlled trials (RCTs) that evaluated the effectiveness and safety of voclosporin + MMF, tacrolimus + MMF, and monotherapy for induction treatment in patients with lupus nephritis. To incorporate direct and indirect evidence from RCTs, we used aBayesian network meta-analysis. Four RCTs, including 936participants, met the inclusion criteria. Tacrolimus + MMF substantially increased the incidence of complete remission relative to that following monotherapy (odds ratio [OR] 2.85; 95% credible interval [CrI] 1.87-4.39). Tacrolimus + MMF was also more effective than voclosporin + MMF (OR 1.43; 95% CrI 0.80-2.57). Tacrolimus + MMF showed the greatest chance of being the optimal treatment for overall response (surface under the cumulative ranking curve [SUCRA] = 0.942), followed by voclosporin + MMF (SUCRA = 0.558) and monotherapy (SUCRA = 0.001). In terms of safety based on severe event rates, monotherapy had the greatest chance of being the safest treatment (SUCRA = 0.903), followed by voclosporin + MMF (SUCRA = 0.517) and tacrolimus + MMF (SUCRA = 0.081). Tacrolimus + MMF and voclosporin + MMF were more effective than monotherapy, and tacrolimus + MMF was the most effective induction treatment for lupus nephritis patients. However, tacrolimus + MMF did pose agreater risk of serious adverse events than monotherapy.

CD62L on blood basophils: a first pre-treatment predictor of remission in severe lupus nephritis.

Basophils were recently shown to contribute to lupus nephritis (LN). This study assessed blood basophil activation markers (BAMs) for the diagnosis of LN severity and as pre-treatment prognostic markers of the response to treatment in patients with severe LN. The diagnostic study included all the patients of a monocentric prospective observational cohort built with consecutive patients diagnosed with LN on the basis of a renal biopsy. The prognostic study selected patients of this cohort according to the following inclusion criteria: ≥18 years old, Class III or IV A ± C ± Class V or pure Class V LN at the time of inclusion and treated with an induction treatment for LN. Clinical data and BAMs were obtained at the time of the kidney biopsy. LN remission status was recorded 12 months after induction therapy initiation. Associations between baseline data and histological severity of LN or LN remission were assessed using logistic regression. No significant association was found between BAMs and the histological severity of LN in 101 patients. Among the 83 patients included in the prognostic study, 64 reached renal remission. CD62L expression on blood basophils at baseline was independently negatively associated with remission at 12 months [odds ratio = 0.26, 95% confidence interval 0.08-0.82, P = 0.02 for quantitative CD62L expression >105 (geometric fluorescent intensity) gMFI]. CD62L <105 gMFI was associated with a probability of 0.87 of LN remission in the next 12 months after the start of induction therapy. Pre-treatment CD62L expression on blood basophils could be a first predictive biomarker of renal response to induction therapy at 12 months in patients with severe LN.

Comparison of treatment response and serious infection using tacrolimus, tacrolimus withmycophenolate mofetil, in comparison tocyclophosphamide as induction treatment for lupus nephritis.

This study evaluated the relative efficacy and safety of tacrolimus, tacrolimus+mycophenolate mofetil (MMF), and cyclophosphamide (CYC) for lupus nephritis. Randomized controlled trials (RCTs) were included to investigate the effectiveness and safety of tacrolimus, tacrolimus+MMF, and CYC as a lupus induction therapy. We performed a Bayesian network meta-analysis of the random effects to incorporate direct and indirect data from RCTs. Four RCTs met the inclusion criteria, giving a sample size of 543 patients. Tacrolimus+MMF had a significantly higher overall response rate (complete plus partial remission) than CYC (OR 4.22, 95% credible interval (CrI) 11.02-29.23) and was more efficacious than tacrolimus (OR 2.02, 95% CrI 0.24-28.51). Tacrolimus had higher overall response than CYC (OR 2.14, 95% CrI 0.38-12.33). Ranking the treatments based on the surface under the cumulative ranking curve (SUCRA) suggested that tacrolimus+MMF was the best treatment by the overall response (SUCRA = 0.876), followed by tacrolimus (SUCRA = 0.533) and CYC (SUCRA = 0.091). Tacrolimus was the least likely to cause serious infections (-SUCRA = 0.758), followed by CYC (SUCRA = 0.398) and tacrolimus+MMF (SUCRA = 0.345). Tacrolimus+MMF was the most effective induction treatment for patients with lupus nephritis, and tacrolimus was the least likely to cause severe infections.

EP16 Challenges in treating new onset systemic lupus erythematosus with lupus nephritis and COVID-19 infection overlap

Case report - IntroductionCOVID-19 infection caused by a novel coronavirus SARS-coV-2 has made the diagnosis and the treatment of inflammatory diseases incredibly challenging. On the one hand, because of its pro-inflammatory state, that may aggravate or trigger flares in autoimmune diseases such as systemic lupus erythematosus (SLE). On the other hand, the risk of an immunosuppressive therapy during the active phase SARS-coV-2 infection that may lead to catastrophic outcomes. We report a case of a 24-year-old female newly diagnosed with SLE during COVID-19 pandemic who developed COVID-19 infection during her induction treatment for lupus nephritis.Case report - Case descriptionA 24-year-old Nepali female, with no past medical history of note, presented to her regional hospital with a history of flu-like symptoms few days ago, peripheral oedema, acute kidney injury with proteinuria and hypertension. Further investigations showed a high titre of double-stranded DNA antibodies, anti-cardiolipin IgM and B2 microglobulin positive and low C3. She also developed a haemolytic anaemia and thrombocytopenia during her admission. She received pulsed steroid therapy and was started on mycophenolate mofetil (MMF) for a probable lupus nephritis awaiting the results of biopsy, which showed later a lupus nephritis Class IV-G with active lesions. She then developed symptoms of COVID-19 infection and had a positive PCR leading to an interruption of her induction therapy. She was recruited to the RECOVERY trial on the lopinavir-ritonavir arm and made a good recovery.Case report - DiscussionIt is well known that viruses can trigger or aggravate auto-immune response in patients predisposed genetically. However, the role of SARS-coV-2 is not elucidated yet. The EULAR COVID-19 registry showed that rheumatoid arthritis and SLE were the most prevalent rheumatic diseases, and there was an increased risk in those who are on moderate to high dose corticosteroids. In patients with SLE and COVID-19 infection, it is agreed by all the national and international rheumatology societies to interrupt their immunosuppressive therapy until the symptoms resolve, especially those with renal involvement or an active disease. Which is the case in our patient. Luckily, she resumed her MMF a month later after a negative PCR and her renal function has continued to improve.Case report - Key learning pointsLupus nephritis is a major risk factor for overall morbidity and mortality in SLE. It requires an early immunosuppressive treatment to induce remission.Randomized clinical trials showed that MMF is at least equally effective as cyclophosphamide in inducing remission and that it has been associated with a reduced risk of infection and amenorrhea. It seems to be a suitable alternative in women of childbearing age. In patients with concomitant COVID-19 disease, immunosuppressive therapy should be paused until the symptoms improve.

Comparative efficacy and safety of mycophenolate mofetil and cyclophosphamide in the induction treatment of lupus nephritis: A systematic review and meta-analysis.

Background:Lupus nephritis (LN) remains a predominant cause of morbidity and mortality in SLE. Here we performed a meta-analysis to evaluate the efficacy and safety of the induction treatment with mycophenolate mofetil (MMF) and cyclophosphamide (CYC) for LN.Methods:Relevant literature was searched by computer from the establishment of the database to November 2019. A meta-analysis was conducted to analysis the efficacy and safety between mycophenolate mofetil and cyclophosphamide as induction therapy in LN patients. The primary end-point was response to urine protein, serum creatinine (Scr) and serum complement C3, and the secondary end-points were complete remission and adverse reactions.Results:Eighteen articles were selected for the final meta-analysis, involving 1989 patients with LN, of which the renal biopsy result could be classified into class III–V according to the standards of WHO/ISN. The results revealed that MMF was superior to CYC in increasing the level of serum complement C3 [SMD = 0.475, 95%CI (0.230–0.719)] and complete remission [RR = 1.231, 95%CI (1.055–1.437)]. Furthermore, the subgroup analysis showed that it was in Asian patients, rather than in Caucasian patients, that CYC exerted a better effect on lowering the level of urine protein (UPRO) than MMF [SMD = 0.405, 95%CI (0.081–0.730)]. Besides, when the initial UPRO level was less than 4 g/day, the effect of CYC was better than MMF [SMD = 0.303, 95%CI (0.014–0.591)]. There was no significant difference between MMF and CYC in improving Scr [SMD = 0.090, 95%CI (−0.060–0.239)]. When it came to the comparison of safety between MMF and CYC, the meta-analysis showed that MMF was superior to CYC in decreasing infection in Caucasian patients [RR = 0.727, 95%CI (0.532–0.993)], reducing the risk of leukopenia and menstrual abnormalities in Asian patients and lowering the frequency of gastrointestinal symptoms [RR = 0.639, 95%CI (0.564–0.724)], independent of race.Conclusions:MMF precedes CYC in improving serum complement C3 and complete remission regardless of race, as well as shows fewer adverse drug reactions in the induction treatment of LN belonging to type III–V. But for Asian patients or those initial UPRO levels are less than 4 g/day, CYC may be superior to MMF.

Induction Treatment of Lupus Nephritis in Asian Countries: Is There a “Best” Therapy?

Induction Treatment of Lupus Nephritis in Asian Countries: Is There a “Best” Therapy?

Multitarget therapy versus intravenous cyclophosphamide in the induction treatment of lupus nephritis: a metaanalysis of randomized controlled trials

Background/aim: Multitarget therapy for lupus nephritis (LN) remains in its exploratory phrase and the recent evidence is insufficient. This study aimed to evaluate the efficacy and safety of mycophenolate mofetil (MMF), tacrolimus (TAC), and steroids (multitarget therapy) versus intravenous cyclophosphamide (IVC) and steroids in induction treatment of LN. Materials and methods: We searched for randomized controlled trials of MMF plus TAC versus IVC in LN using PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, the China Biology Medicine Database, and the China National Knowledge Infrastructure Database. We assessed the retrieved citations and selected studies according to predefined inclusion and exclusion criteria. Results: In total, we identified 8 trials including 801 patients. The metaanalysis revealed that overall multitarget therapy is more effective at inducing complete renal remission compared with IVC (RR: 1.94, 95% CI: 1.61-2.33; P < 0.00001). In terms of LN classification, multitarget therapy exhibited superiority compared with IVC for inducing complete remission of class IV LN (RR: 1.52, 95% CI: 1.10- 2.08; P = 0.01), class V LN (RR: 4.24, 95% CI: 1.30-13.88; P = 0.02), and class V+IV LN (RR: 2.29, 95% CI: 1.45-3.62; P = 0.0004); however, no superiority was noted for class III LN or class V+III LN. The rates of gastrointestinal symptoms, abnormal liver function, leukopenia, and irregular menstruation were significantly reduced in the multitarget therapy group compared with the IVC group for LN. Nevertheless, the multitarget therapy group more frequently exhibited new-onset hypertension compared with the IVC group. Conclusion: Multitarget therapy is more effective than IVC in the induction treatment of LN in Chinese patients and exhibits a better safety profile.

Immunosuppressive Treatment for Proliferative Lupus Nephritis: Summary of a Cochrane Review

Immunosuppressive Treatment for Proliferative Lupus Nephritis: Summary of a Cochrane Review

An Update on Therapies for Proliferative Lupus Nephritis: How Certain Can We Be About the Evidence?

An Update on Therapies for Proliferative Lupus Nephritis: How Certain Can We Be About the Evidence?

Mycophenolate Mofetil versus Cyclophosphamide for Induction Treatment of Lupus Nephritis

Recent studies have suggested that mycophenolate mofetil (MMF) may offer advantages over intravenous cyclophosphamide (IVC) for the treatment of lupus nephritis, but these therapies have not been compared in an international randomized, controlled trial. Here, the comparison of MMF and IVC as induction treatment for active lupus nephritis in a multinational, two-phase (induction and maintenance) study was shown in the different study. Lupus nephritis (LN) occurs in up to 60% of adults with systemic lupus erythematosus (SLE) and predicts poor survival. The prevalence of SLE and LN and treatment response vary by age, gender, location, and race/ethnicity; LN is especially common in black and Hispanic patients in the United States. MMF was at least as effective as IVC in induction treatment in previous trials in Hong Kong, Malaysia, China, and the United States. Meta-analyses of these and smaller trials suggested that MMF may offer advantages over IVC, but they have not yet been compared in an international randomized, controlled trial. Many comparative studies were undertaken in patients with LN, a two-part trial to assess the efficacy and safety of MMF as induction therapy and subsequently as maintenance therapy for LN. This article will describe the comparison of MMF with IVC, both with corticosteroids.Anwer Khan Modern Medical College Journal Vol. 9, No. 1: Jan 2018, P 63-67

Multitarget therapy of mycophenolate mofetil and cyclosporine A for induction treatment of refractory lupus nephritis.

Standard induction therapy for lupus nephritis (LN) with mycophenolate mofetil (MMF) or cyclophosphamide (CYC) is often ineffective. Evidence on rescue induction regimens is scarce. We analyzed efficacy and tolerability of multitarget immunosuppression with MMF and cyclosporine A (CsA) as induction treatment for LN (class III/IV/V) refractory to CYC and/or MMF. We included all six refractory LN patients (class IV = 3, class V = 2, class III = 1) from our 400-patient tertiary Lupus Clinic observed between 2012 and 2015. Four patients had previously received pulse CYC. All six received MMF as first or second induction therapy and CsA was added once failure to reach remission was established. Daily dose of MMF was 2-3 g and CsA was dosed up to 2.6-3.7 mg/kg/day. Mean proteinuria was reduced from 2407 mg/24 hours at the start of the MMF+CsA regimen to 544 mg/day after six months. The mean prednisolone dose was reduced from 17.5 to 6 mg/day after six months of MMF+CsA. Four patients achieved a complete renal response, one patient had a partial renal response and one failed to respond. None of the patients presented with adverse events. These data suggest that adding CsA to MMF can induce complete remission of refractory LN and is well tolerated.

Multitarget Therapy for Maintenance Treatment of Lupus Nephritis.

Our previous studies showed that multitarget therapy is superior in efficacy to intravenous cyclophosphamide as an induction treatment for lupus nephritis in Asian populations. We conducted an open label, multicenter study for 18 months as an extension of the prior induction therapy trial in 19 renal centers in China to assess the efficacy and safety of multitarget maintenance therapy in patients who had responded at 24 weeks during the induction phase. Patients who had undergone multitarget induction therapy continued to receive multitarget therapy (tacrolimus, 2-3 mg/d; mycophenolate mofetil, 0.50-0.75 g/d; prednisone, 10 mg/d), and patients who had received intravenous cyclophosphamide induction treatment received azathioprine (2 mg/kg per day) plus prednisone (10 mg/d). We assessed the renal relapse rate during maintenance therapy as the primary outcome. We recruited 116 patients in the multitarget group and 90 patients in the azathioprine group. The multitarget and azathioprine groups had similar cumulative renal relapse rates (5.47% versus 7.62%, respectively; adjusted hazard ratio, 0.82; 95% confidence interval, 0.25 to 2.67; P=0.74), and serum creatinine levels and eGFR remained stable in both groups. The azathioprine group had more adverse events (44.4% versus 16.4% for multitarget therapy; P<0.01), and the multitarget group had a lower withdrawal rate due to adverse events (1.7% versus 8.9% for azathioprine; P=0.02). In conclusion, multitarget therapy as a maintenance treatment for lupus nephritis resulted in a low renal relapse rate and fewer adverse events, suggesting that multitarget therapy is an effective and safe maintenance treatment for patients with lupus nephritis.

Antiphospholipid Antibodies in Lupus Nephritis

Lupus nephritis (LN) is a major manifestation of systemic lupus erythematosus (SLE). It remains unclear whether antiphospholipid antibodies (aPL) alter the course of LN. We thus investigated the impact of aPL on short-term and long-term renal outcomes in patients with LN. We assessed levels of aPL cross-sectionally in SLE patients diagnosed with (n = 204) or without (n = 294) LN, and prospectively in 64 patients with active biopsy-proven LN (52 proliferative, 12 membranous), before and after induction treatment (short-term outcomes). Long-term renal outcome in the prospective LN cohort was determined by the estimated glomerular filtration rate (eGFR) and the Chronic Kidney Disease (CKD) stage, after a median follow-up of 11.3 years (range: 3.3–18.8). Cross-sectional analysis revealed no association between LN and IgG/IgM anticardiolipin or anti-β2-glycoprotein I antibodies, or lupus anticoagulant. Both aPL positivity and levels were similar in patients with active LN and non-renal SLE. Following induction treatment for LN, serum IgG/IgM aPL levels decreased in responders (p<0.005 for all), but not in non-responders. Both at active LN and post-treatment, patients with IgG, but not IgM, aPL had higher creatinine levels compared with patients without IgG aPL. Neither aPL positivity nor levels were associated with changes in eGFR from either baseline or post-treatment through long-term follow-up. Moreover, aPL positivity and levels both at baseline and post-treatment were similar in patients with a CKD stage ≥3 versus 1–2 at the last follow-up. In conclusion, neither aPL positivity nor levels were found to be associated with the occurrence of LN in SLE patients. However, IgG aPL positivity in LN patients was associated with a short-term impairment of the renal function while no effect on long-term renal outcome was observed. Furthermore, IgG and IgM aPL levels decreased following induction treatment only in responders, indicating that aPL levels are affected by immunosuppressive drugs in a response-dependent manner.

Moderator's view: Cyclophosphamide in lupus nephritis.

Mycophenolate mofetil was recently accepted as the effective induction treatment of lupus nephritis, with the potential to replace cyclophosphamide or at least expand our therapeutic armamentarium in patients with this lifelong disease often requiring repeated induction treatment of its relapses. Compared with cyclophosphamide, mycophenolate may be more effective in black patients, and the risk of gonadotoxicity may be significantly lower in mycophenolate-treated subjects. However, experience with mycophenolate in severe lupus nephritis is still limited and we also have insufficient data on the long-term outcome of mycophenolate-treated patients. Treatment with mycophenolate is more expensive than with cyclophosphamide, which may limit its use, especially in low- and middle-income countries. The efficacy of mycophenolate mofetil may be more dependent on the patient's compliance compared with intravenous cyclophosphamide pulses. Low-dose cyclophosphamide remains an effective and relatively safe induction treatment of active lupus nephritis, but to decrease its cumulative toxicity, repeated exposure to cyclophosphamide in relapsing patients should be (if possible) avoided.

Analysis of the effectiveness and safety of rituximab in patients with refractory lupus nephritis: a chart review.

Lupus nephritis is a life-threatening complication of systemic lupus erythematosus. The standard treatment for this condition, including corticosteroids and cyclophosphamide, results in a 70 % remission rate at 12 months, but it is also associated with significant morbidity. Rituximab, a chimeric anti-CD20 antibody, could be useful, given the central role of B cells in the pathogenesis of systemic lupus erythematosus. Case reports and retrospective series have reported that rituximab is effective for refractory lupus nephritis. However, the double-blind, placebo-controlled LUNAR trial failed to meet its end point. We studied clinical, biological, and immunological data on 17 patients who received rituximab as an induction treatment for refractory lupus nephritis at the University Hospital Center of Bordeaux. A complete treatment response was defined as a normal serum creatinine with inactive urinary sediment and 24-h urinary albumin <0.5 g and a partial response (PR) as a >50 % improvement in all of the renal parameters that were abnormal at baseline, with no deterioration in any parameter. Seventeen patients received rituximab as induction treatment for lupus nephritis refractory to standard treatment by cyclophosphamide. After a follow-up of 12 months, complete or partial renal remission was achieved in 53 % patients. Rituximab therapy resulted in a significant improvement in proteinuria and steroid dose tapering in all patients. Rituximab should be considered as a treatment option for refractory lupus glomerulonephritis.