Search

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: CNS demyelinating syndromes occurring in the context of SLE may represent a manifestation of neuropsychiatric lupus, or an overlap of SLE and multiple sclerosis (MS). We evaluated prospectively patients presenting with demyelinating syndrome for clinical and serological evidence of SLE and characterized the evolution of their clinical syndrome to a defined disease., Methods: Patients with CNS demyelinating syndromes not fulfilling the criteria for MS were evaluated in a rheumatology unit for features of SLE and followed longitudinally (enrolment period 2016-20). Clinical, laboratory and neuroimaging data were recorded at every visit, following multidisciplinary evaluation. At end of follow-up, patients were assessed for their final neurological and rheumatological diagnosis, and classified accordingly., Results: A total of 79 patients were included in the study [91.1% female, mean (s.d.) age at first demyelinating episode 38.4 (10.3) years, median (interquartile range) observation period 39 (57) months]. At last follow-up, 38 patients (48.1%) had evolved into MS. Of the remaining patients, 7 (17.1%) had SLE, while 34 (82.9%) had features of systemic autoimmunity without fulfilling classification criteria for SLE. The most common rheumatological features of these patients were inflammatory arthritis (73.5%), acute cutaneous lupus (47.1%) and positive ANA (72.1%). Importantly, these patients were less likely to have elevated IgG index (odds ratio 0.11, 95% CI 0.04, 0.32) and positive oligoclonal bands (odds ratio 0.21, 95% CI 0.08, 0.55)., Conclusion: A significant number of patients with demyelination do not fulfill criteria for either MS or SLE at follow-up. These patients exhibit lupus-like autoimmune features and may represent a distinct entity, 'demyelination with autoimmune features'., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Clinical heterogeneity, unpredictable course and flares are characteristics of systemic lupus erythematosus (SLE). Although SLE is-by and large-a systemic disease, occasionally it can be organ-dominant, posing diagnostic challenges. To date, diagnosis of SLE remains clinical with a few cases being negative for serologic tests. Diagnostic criteria are not available and classification criteria are often used for diagnosis, yet with significant caveats. Newer sets of criteria (European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019) enable earlier and more accurate classification of SLE. Several disease endotypes have been recognised over the years. There is increased recognition of milder cases at presentation, but almost half of them progress overtime to more severe disease. Approximately 70% of patients follow a relapsing-remitting course, the remaining divided equally between a prolonged remission and a persistently active disease. Treatment goals include long-term patient survival, prevention of flares and organ damage, and optimisation of health-related quality of life. For organ-threatening or life-threatening SLE, treatment usually includes an initial period of high-intensity immunosuppressive therapy to control disease activity, followed by a longer period of less intensive therapy to consolidate response and prevent relapses. Management of disease-related and treatment-related comorbidities, especially infections and atherosclerosis, is of paramount importance. New disease-modifying conventional and biologic agents-used alone, in combination or sequentially-have improved rates of achieving both short-term and long-term treatment goals, including minimisation of glucocorticoid use., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To update the 2012 EULAR/ERA-EDTA recommendations for the management of lupus nephritis (LN)., Methods: Following the EULAR standardised operating procedures, a systematic literature review was performed. Members of a multidisciplinary Task Force voted independently on their level of agreeement with the formed statements., Results: The changes include recommendations for treatment targets, use of glucocorticoids and calcineurin inhibitors (CNIs) and management of end-stage kidney disease (ESKD). The target of therapy is complete response (proteinuria <0.5-0.7 g/24 hours with (near-)normal glomerular filtration rate) by 12 months, but this can be extended in patients with baseline nephrotic-range proteinuria. Hydroxychloroquine is recommended with regular ophthalmological monitoring. In active proliferative LN, initial (induction) treatment with mycophenolate mofetil (MMF 2-3 g/day or mycophenolic acid (MPA) at equivalent dose) or low-dose intravenous cyclophosphamide (CY; 500 mg × 6 biweekly doses), both combined with glucocorticoids (pulses of intravenous methylprednisolone, then oral prednisone 0.3-0.5 mg/kg/day) is recommended. MMF/CNI (especially tacrolimus) combination and high-dose CY are alternatives, for patients with nephrotic-range proteinuria and adverse prognostic factors. Subsequent long-term maintenance treatment with MMF or azathioprine should follow, with no or low-dose (<7.5 mg/day) glucocorticoids. The choice of agent depends on the initial regimen and plans for pregnancy. In non-responding disease, switch of induction regimens or rituximab are recommended. In pure membranous LN with nephrotic-range proteinuria or proteinuria >1 g/24 hours despite renin-angiotensin-aldosterone blockade, MMF in combination with glucocorticoids is preferred. Assessment for kidney and extra-renal disease activity, and management of comorbidities is lifelong with repeat kidney biopsy in cases of incomplete response or nephritic flares. In ESKD, transplantation is the preferred kidney replacement option with immunosuppression guided by transplant protocols and/or extra-renal manifestations. Treatment of LN in children follows the same principles as adult disease., Conclusions: We have updated the EULAR recommendations for the management of LN to facilitate homogenization of patient care., Competing Interests: Competing interests: AF reports personal fees from GSK, Abbvie, Amgen, Enorasis, Roche and Genesis Pharma, outside the submitted work. HJA reports personal fees from GSK, Astra Zeneca and Janssen, during the conduct of the study; personal fees from Secarna, Inositec, Previpharma and Noxxon, outside the submitted work. MA reports honoraria fees from GSK and Roche, outside the submitted work; FH reports honoraria fees from GSL, outside the submitted work. MP reports personal fees from Otsuka, grants and personal fees from Alexion, personal fees from Retrophin, outside the submitted work. YKOT reports grants from GSK, personal fees from Aurinia Pharmaceuticals, personal fees from Novartis, during the conduct of the study. MT reports grants from Abbvie, BMS, Novartis, Pfize and Roche and honoraria fees from Novartis, outside the submitted work. DJ reports personal fees from Astra-Zeneca, Aurinia, Boehringer-Ingelheim, grants and personal fees from Chemocentryx, GSK, Roche/Genentech, and Sanofi-Genzyme, personal fees and other from Vifor, outside the submitted work., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Low disease activity is a validated target of current systemic lupus erythematosus (SLE) therapy. The aim of this study was to assess the ability of belimumab to achieve low disease activity states in real-life settings., Methods: Multicentre prospective observational study of consecutive SLE patients receiving belimumab for at least 3 months, due to active disease refractory to at least one conventional immunosuppressant. Disease activity, including the recently defined lupus low disease activity state (LLDAS) and remission (clinical SLEDAI-2K = 0), accrual of organ damage, flares and side effects were documented., Results: Ninety-one patients were included [94.5% women, mean (SD) age 45.9 (12.5) years]. Most frequent manifestations were arthritis (76.7%), rash (72.5%), serologic activity (low C3/C4 and/or high anti-dsDNA; 54.9%), hair loss (47.2%) and mucosal ulcers (27.5%). Median (range) duration of treatment was 10.5 (3.0-42.1) months. Belimumab significantly decreased average SLEDAI-2K, physician global assessment (PGA) and daily prednisone dose over time, as early as 3 months after initiation, with over 20% of patients discontinuing corticosteroids. Although reduction in clinical (i.e., excluding serology) SLEDAI-2K was more pronounced in patients who were serologically active (from 8 to 1.5 at 12 months) as compared to serologically inactive (from 6 to 4) at baseline, attainment of LLDAS did not differ between the two groups and was reached by more than 40% of completer patients after 9-12 months. In addition, the number of flares and severe flares was reduced by 62% and 50%, respectively, during the first 12 months of treatment. Twenty patients (22.0%) discontinued treatment due to inadequate response and two due to side effects potentially related to the drug., Conclusions: In real-life, belimumab is efficacious in achieving low disease activity in over 40% of unselected patients, in combination with reduction of corticosteroid dosage and number of flares. Both serologically active and inactive patients respond to the drug., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Lupus nephritis (LN) treatment requires an initial intensive period of therapy followed by a long-term maintenance treatment in order to stabilize disease control and eventually reach renal remission. In this section, Authors discuss the feasibility of safely lowering and even suspending maintenance therapy in LN patients having entered remission, highlighting hurdles in predicting the depth and durability of disease quiescence together with the need for minimizing potentially toxic therapies. Even though no firm conclusions can still be drawn, the treating physician has to find the wise balance between disease control and treatment-related drawbacks by following patients closely and recognizing as early as possible the ones who are likely to reach a deep and durable renal remission; there is consensus that is these are the only patients in whom a potential safe complete withdrawal can be foreseen so far., (Copyright © 2017. Published by Elsevier B.V.)

Objectives: The coexistence of systemic lupus erythematosus (SLE) and multiple sclerosis (MS) in the same individual has rarely been described. Our objective was to report on the prevalence, clinical characteristics, and prognosis of cases fulfilling the criteria for both SLE and MS., Methods: We utilized existing patient cohorts from the Departments of Rheumatology and Neurology, University of Crete, and screened patients diagnosed with either SLE (n = 728) or MS (n = 819) for features of both diseases. The clinical, laboratory, and neuroimaging findings were assessed., Results: We identified nine patients who fulfilled the diagnostic criteria for both SLE and MS, corresponding to a prevalence rate of 1.0-1.2% in each cohort. All patients were women, with an average age at SLE diagnosis of 42.1 years (range: 34-56 years). The diagnosis of SLE preceded the development of MS in five patients, with a time lag ≤ 5 years in four of them. Initial presentation of MS included spinal symptoms in seven patients. All patients had features of mild SLE with predominantly cutaneous, mucosal, and musculoskeletal manifestations. Accordingly, therapeutic decisions were mainly guided by the severity of the neurological syndrome. During the median follow-up of 4 years (range: 1-10 years), three patients remained stable and the remaining experienced gradual deterioration in their neurological status. SLE remained quiescent in all patients while on standard immunomodulatory MS therapy., Conclusions: Occurrence of both diseases in the same individual is rare, corroborating data that suggest distinct molecular signatures. SLE and MS coexistence was not associated with a severe phenotype for either entity., (© 2013 Published by Elsevier Inc.)

Objectives: To develop recommendations for the management of adult and paediatric lupus nephritis (LN)., Methods: The available evidence was systematically reviewed using the PubMed database. A modified Delphi method was used to compile questions, elicit expert opinions and reach consensus., Results: Immunosuppressive treatment should be guided by renal biopsy, and aiming for complete renal response (proteinuria <0.5 g/24 h with normal or near-normal renal function). Hydroxychloroquine is recommended for all patients with LN. Because of a more favourable efficacy/toxicity ratio, as initial treatment for patients with class III-IV(A) or (A/C) (±V) LN according to the International Society of Nephrology/Renal Pathology Society 2003 classification, mycophenolic acid (MPA) or low-dose intravenous cyclophosphamide (CY) in combination with glucocorticoids is recommended. In patients with adverse clinical or histological features, CY can be prescribed at higher doses, while azathioprine is an alternative for milder cases. For pure class V LN with nephrotic-range proteinuria, MPA in combination with oral glucocorticoids is recommended as initial treatment. In patients improving after initial treatment, subsequent immunosuppression with MPA or azathioprine is recommended for at least 3 years; in such cases, initial treatment with MPA should be followed by MPA. For MPA or CY failures, switching to the other agent, or to rituximab, is the suggested course of action. In anticipation of pregnancy, patients should be switched to appropriate medications without reducing the intensity of treatment. There is no evidence to suggest that management of LN should differ in children versus adults., Conclusions: Recommendations for the management of LN were developed using an evidence-based approach followed by expert consensus.

The treatment of lupus nephritis has seen significant advances during the past decade mainly due to the publication of well-designed randomized clinical trials (RCTs). The choice of treatment is guided by the histopathologic classification but is also influenced by demographic, clinical, and laboratory characteristics that allow for the identification of patients at risk for more aggressive disease. For the induction arm, low-dose cyclophosphamide regimens and mycophenolate mofetil have been validated as alternatives to the established National Institutes of Health regimen of high-dose cyclophosphamide; for the maintenance phase, azathioprine and mycophenolate compete for treatment of first choice. Rituximab is efficacious in real-life clinical practice but ineffective in clinical trials. The role of recently approved belimumab in lupus nephritis eagerly awaits further documentation. Aggressive management of comorbid conditions, such as hypertension and dyslipidemia, is of utmost importance. Here, we review the latest advances in lupus nephritis therapy with a focus on recent RCTs as well as new biologic agents under development. Furthermore, we propose a therapeutic algorithm in an effort to facilitate clinical decision-making in this gradually changing landscape. Upcoming European and American recommendations should provide further clarification.

Therapy of systemic lupus erythematosus has been facing the paradox of an overwhelming rate of trials testing novel potential therapeutic agents and the lack of US FDA approval of a single new drug for over five decades. Heterogeneity in disease phenotype, concomitant immunosuppressive medication and a lack of unequivocal hard end points for clinical trials have proven to be significant obstacles in establishing efficacy of candidate therapies. Nevertheless, combination regimens with already existing agents have shown efficacy with acceptable safety profiles, mainly in cases of refractory to conventional treatment disease. At the same time, positive results from trials with belimumab, an antibody that targets B cells, opened the way for approval of this agent for the treatment of lupus and lends hope for a new era in systemic lupus erythematosus therapeutics. Here, we review the latest advances in systemic lupus erythematosus therapy, focusing on the balance between efficacy and safety for combination therapeutic regimens and biologics under development.

Neuropsychiatric events are common in patients with systemic lupus erythematosus (SLE), but less than one-third of these events can be directly attributed to SLE. Increased generalized SLE disease activity or damage, previous or concurrent major neuropsychiatric SLE (NPSLE) events, and persistently positive moderate-to-high antiphospholipid antibody titers are established risk factors, and their presence could facilitate proper attribution to the disease itself. Diagnostic evaluation is guided by the presenting manifestation; MRI is used to visualize brain or spinal pathologies. For neuropsychiatric events believed to reflect an immune or inflammatory process, or when these events occur in the context of active generalized disease, evidence (primarily from uncontrolled studies) supports the use of glucocorticoids alone or in combination with immunosuppressive therapy. Antiplatelet and/or anticoagulation therapy is recommended for NPSLE manifestations related to antiphospholipid antibodies, especially for thrombotic cerebrovascular disease. For the future, we anticipate that novel biomarkers and advanced neuroimaging tests will better define the underlying pathologic mechanisms of SLE-related neuropsychiatric disease, and help guide therapeutic decisions.

The introduction of new therapeutic modalities, such as biologic agents, for the treatment of lupus nephritis has re-energized research into this disorder, enabling investigators to formulate evidence-based recommendations. Thus, it is now widely accepted that the management of lupus nephritis involves a period of intensive induction therapy, followed by a longer period of less-intensive maintenance therapy. Risk stratification, based on histologic, demographic, clinical and laboratory characteristics, allows the identification of patients at high risk of renal dysfunction, for whom aggressive therapy is likely to be the most beneficial. New studies and meta-analyses comparing mycophenolate mofetil with cyclophosphamide have confirmed the efficacy of the former for induction and maintenance therapy--particularly induction therapy, owing to its favorable toxicity profile; however, claims of efficacy superior to that of cyclophosphamide require additional documentation. Nonetheless, an increasing number of physicians use mycophenolate mofetil as induction therapy for most cases of proliferative lupus nephritis, while reserving cyclophosphamide for the most severe cases. No evidence yet indicates that mycophenolate mofetil is better than azathioprine for the maintenance of remission. For patients who relapse or who are unable to be treated with these agents, rituximab seems to offer some benefit with an acceptable toxicity profile. This article summarizes the advances in the management of lupus nephritis since our 2005 Review.

Background: The optimal therapy for lupus nephritis has been the subject of considerable debate., Objective: To provide evidence- and expert-based recommendations., Methods: To review the literature and the European League Against Rheumatism recommendations., Results: Risk stratification based on histological, demographical, clinical and laboratory characteristics allows the identification of patients at high risk for loss of renal function, and thus more likely to benefit from more aggressive therapy. Achieving remission within the first months of treatment, irrespective of the agent used, correlates with good long-term renal outcomes; maintenance of remission can be achieved with less toxic therapies. Aggressive management of atherosclerosis risk factors and renoprotective therapy for those patients with chronic renal disease improve long-term survival and prognosis.

The optimum therapy for patients with lupus nephritis is a hotly debated topic. Prospective randomized studies in patients with proliferative lupus nephritis have established the superiority of cyclophosphamide to azathioprine, both of which are used in combination with corticosteroids. Although high-dose, intermittent administration of cyclophosphamide (pulse therapy) has significantly reduced the toxicity associated with this drug, premature ovarian failure and infections remain considerable problems. Short-term to intermediate-term, randomized controlled trials have shown that mycophenolate mofetil is a good option for the induction and maintenance of remission in lupus nephritis patients. Additional longer-term trials involving more patients and stricter outcomes based on renal function are needed, however, before claims that mycophenolate mofetil is superior to cyclophosphamide can be substantiated. Until such data are available, physicians caring for patients with lupus nephritis can use mycophenolate mofetil as induction or maintenance therapy for selected patients under close observation. Small noncontrolled trials with short-term follow-up suggest that up to 50% of patients who are refractory to cyclophosphamide might have a clinically significant response to rituximab, a monoclonal antibody directed against B cells.

Background: Fludarabine, a purine antimetabolite with potent immunosuppressive properties, has previously been associated with the development of transfusion-associated GVHD (TA-GVHD) in patients with hematologic malignancies. Its role as a risk factor for TA-GVHD in patients without underlying leukemia or lymphoma is uncertain., Study Design and Methods: A 42-year-old female with refractory lupus nephritis received three monthly cycles of fludarabine (30 mg/m2/day on Days 1-3) and cyclophosphamide (500 mg/m2 on Day 1). Three months after the last dose of fludarabine, she received 2 units of packed RBCs and 6 units of pooled random platelets, none of which were irradiated. Two weeks later, fever, rash, aminotransferase elevations, hyperbilirubinemia, and pancytopenia developed., Results: Marrow biopsy showed severe aplasia and skin biopsy was consistent with GVHD. Allele-level HLA typing on circulating lymphocytes revealed extra HLA alleles not present in her pretreatment sample, but identical to the HLA haplotypes of an unrelated platelet donor. Treatment with antithymocyte globulin, cyclosporine, and prednisone was followed by preparatory conditioning for a PBPC transplant from an HLA-identical sibling, but the patient died of disseminated candidiasis before transplant., Conclusions: Fludarabine and other purine analogs are increasingly used in the treatment of disorders other than hematologic malignancy, such as autoimmune disease. The occurence of TA-GVHD after fludarabine therapy in a patient with lupus strongly suggests that this drug is sufficiently immunoablative to be an independent risk factor for TA-GVHD. Irradiation of blood components should be considered in all patients who receive fludarabine therapy.

Background: Hematologic manifestations are common in systemic lupus erythematosus (SLE), either at initial presentation or during the course of the disease, but data regarding their natural history are scarce. Objective: To describe the characteristics, treatments, and outcomes of severe hematological manifestations in a large cohort of lupus patients. Methods: Retrospective cohort study of patients in the "Attikon" lupus cohort who had a history of a severe hematologic manifestation, defined as autoimmune hemolytic anemia (AIHA) with hemoglobin < 8 g/dL, thrombocytopenia with platelet count < 30,000/mm3, Evans syndrome with hemoglobin < 8 g/dL, and/or platelet count < 30,000/mm3, neutropenia with < 500 neutrophils/mm3, thrombotic microangiopathy (TMA)/thrombotic thrombocytopenic purpura (TTP)-like syndrome, or macrophage activation syndrome (MAS). Demographic and clinical characteristics, treatments, and outcomes were recorded. Results: From over 300 patients with hematologic manifestations, 41 qualified as severe (70.7% women, mean [SD] age at SLE diagnosis 42.6 [18.0] years). Hematologic manifestations preceded SLE diagnosis in 13 patients (31.7%), was concomitant to SLE diagnosis in 16 patients (39%), and occurred during the course of the disease in 12 (29.3%) patients, with a mean (SD) disease duration of 8.7 (5.5) years. Thrombocytopenia was the most common severe hematological manifestation (56.1%), followed by AIHA (17.1%) and TTP-like syndrome (12.2%). For initial treatment, all patients were treated with glucocorticoids (GC), while rituximab and cyclophosphamide were the most frequently used immunosuppressive agents. Following initial treatment, relapse occurred in 22 patients (53.7%). Compared to patients that did not relapse, those that relapsed had less often received concomitant immunosuppressive agents following treatment of initial episode (n = 17/23, 73.9% vs 5/17, 29.4%, p = 0.005). Conclusion: Severe hematologic disease in SLE has a high risk of relapse, which may be mitigated by the early institution of GC-sparing agents. [ABSTRACT FROM AUTHOR]

Objective. To compare the European League Against Rheumatism (EULAR) recommendations for the management of NPSLE with usual care in two tertiary centres and to detect potential pitfalls in their use for diagnosis and treatment. Methods. A chart-based review of NPSLE manifestations was conducted in two European centres. Diagnostic and treatment decisions were compared against the EULAR recommendations for general NPSLE and specific manifestations. Results. We studied a total of 94 patients who experienced 123 lupus-related neuropsychiatric events over 10 years. In 80% of the events, at least one EULAR-defined risk factor (previous NPSLE, generalized disease activity or aPL positivity) was present. Overall, there was good concordance between clinical care and recommendations for diagnosis and treatment (68.7% and 62.7% of events, respectively). Brain MRI was performed in the absence of a clear EULAR recommendation in 42.9% of events; therein, it was more frequently normal compared with imaging performed according to the recommendations (52.4% vs 18.5%, P = 0.008), and it did not influence management. Among patients reporting cognitive dysfunction, only 27.8% underwent the recommended neuropsychological assessment. In line with the recommendations, immunosuppressants were more frequently given in events suggestive of an inflammatory process (80.5% vs 47.6% in non-inflammatory events, P<0.001). Notably, 52% of cerebrovascular events were managed with combined immunosuppressive/antithrombotic therapy due to either coexisting generalized lupus activity or recurrence despite prior antithrombotic treatment. Conclusion. Despite good concordance between EULAR recommendations for NPSLE and usual clinical practice, we identified a number of issues (such as overutilization of brain MRI, suboptimal evaluation of cognitive dysfunction, and frequent use of immunosuppressives in cerebrovascular disease) that need to be investigated further. [ABSTRACT FROM AUTHOR]

Background: Controlled trials in lupus nephritis have demonstrated that cyclophosphamide therapy is superior to corticosteroid therapy alone. The long-term effectiveness and side-effect profiles of pulse immunosuppressive regimens warrant further study.Objective: To define the long-term risk and benefit of monthly treatment with boluses of methylprednisolone, cyclophosphamide, or both.Design: Extended follow-up (median, 11 years) of a randomized, controlled trial.Setting: U.S. government research hospital.Patients: 82 patients with proliferative lupus nephritis.Measurements: Rates of treatment failure (defined as need for supplemental immunosuppressive therapy or doubling of serum creatinine concentration, or death) and adverse events.Results: In an intention-to-treat survival analysis, the likelihood of treatment failure was significantly lower in the cyclophosphamide (P = 0.04) and combination therapy (P = 0.002) groups than in the methylprednisolone group. Combination therapy and cyclophosphamide therapy alone did not differ statistically in terms of effectiveness or adverse events. Of patients who completed the protocol (n = 65), the proportion of patients who had doubling of serum creatinine concentration was significantly lower in the combination group than in the cyclophosphamide group (relative risk, 0.095 [95% CI, 0.01 to 0.842]).Conclusion: With extended follow-up, pulse cyclophosphamide continued to show superior efficacy over pulse methylprednisolone alone for treatment of lupus nephritis. The combination of pulse cyclophosphamide and methylprednisolone appears to provide additional benefit over pulse cyclophosphamide alone and does not confer additional risk for adverse events. [ABSTRACT FROM AUTHOR]

Objective: To determine the risk for secondary amenorrhea after pulse cyclophosphamide therapy in premenopausal women with systemic lupus erythematosus.Design: Controlled, retrospective clinical study.Setting: Government referral-based research hospital.Patients: Thirty-nine women younger than 40 years treated with pulse cyclophosphamide therapy for active lupus nephritis or neuropsychiatric lupus. Sixteen women who received pulses of intravenous methylprednisolone were controls.Interventions: Sixteen patients received pulse cyclophosphamide (0.5 to 1.0 g/m2 body surface area) monthly for a total of 7 doses (short-CY), and 23 patients received 15 or more doses (long-CY). Control patients were treated with monthly pulses of methylprednisolone (1.0 g/m2) for a total of nine doses.Measurements: Rates of amenorrhea were evaluated according to duration of treatment (number of doses) and age at the initiation of pulse therapy.Results: Two of 16 patients (12%) in the Short-CY group and 9 of 23 (39%) in the long-CY group developed sustained amenorrhea (P = 0.07). Rates of sustained amenorrhea (short- and long-CY) according to age at the start of pulse therapy were: < or = 25 years, 2/16 (12%); 26 to 30 years, 4/15 (27%); > or = 31 years, 5/8 (62%) (P = 0.04). The increased risk for sustained amenorrhea in patients treated with long-CY was most evident in patients older than 25 years (short-CY [2/12] compared with long-CY [7/11]; P = 0.03). Three other patients with short-CY had reversal of amenorrhea fewer than 12 months after cessation of therapy. Amenorrhea was not observed in any of the 16 control patients.Conclusions: Intermittent pulse cyclophosphamide therapy in patients with systemic lupus erythematosus is associated with sustained amenorrhea, which is related to both age and number of doses of cyclophosphamide. [ABSTRACT FROM AUTHOR]

Provides information on membranous nephropathy. Stages; Causes; Immunosuppressive agents used for the disease.

Tumor necrosis factor α (TNF-α) blockade has emerged as a useful therapy for collagen vascular diseases or graft-vs-host disease. Fungal Infections complicating such therapy have been reported sporadically. MEDLINE and PubMed databases (from January 1, 1966, to June 1, 2007) were searched for reports of Invasive fungal Infections (IFIs) associated with the 3 available antl-TNF-α agents, le, infliximab, etanercept, and adalimumab. Of the 281 cases of IFI associated with TNF-α Inhibition, 226 (80%) were associated with Infliximab, 44 (16%) with etanercept, and 11 (4%) with adailmumab. Fungal Infections associated with infliximab occurred a median of 55 days (Interquartile range [IQR], 15-140 days) after Initiation of therapy and 3 infusions of the medication (IQR, 2-5), whereas those associated with etanercept occurred a median of 144 days (1QR, 46-240 days) after initiation of therapy. The median age of patients was 58 years (1QR, 44-68 years), and 62% were male. Use of at least I other Immunosup-pressant medication, typically a systemic corticosterold, was reported during the course of the fungal Infection In 102 (98%) of the 104 patients for whom data were available. The most prevalent IFis were histoplasmosis (n=84 [30%]), candidiasis (n=64 [23%]), and aspergiliosis (n=64 [23%]). Pneumonia was the most common pattern of Infection. Of the 90 (32%) of 281 cases for which outcome Information was available, 29 fatalities (32%) were recorded. Tumor necrosis factor a blockade Is associated with IFI across a range of host groups. A high index of suspicion In patients treated with TNF-α antagonists Is recommended because the course of such Infections can be serious or fulminant, and rapid access to health care should be provided. Surveillance of IFIs complicating TNF-a blockade and other biologic therapies Is war- ranted through well-organized prospective patient registries. [ABSTRACT FROM AUTHOR]