Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0024141 (systemic lupus erythematosus)
44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Improved patient survival following lupus nephritis with the institution of corticosteroids, immunosuppressants and renal replacement therapy allows greater emphasis on long-term management issues. In particular, the recent focus has been on therapies to treat nephritis with fewer adverse effects of cyclophosphamide-including immunosuppressive regimens. Mycophenolate mofetil (MMF) has been used in the field of transplantation for more than 10 years. Following initial anecdotal reports describing benefits of MMF in the treatment of lupus nephritis, randomized, controlled trials have established a role for MMF in the treatment of lupus nephritis. MMF use to treat other lupus manifestations has been evaluated only in anecdotal case reports or series with few well-designed trials. Issues complicating clinical trial design in lupus including appropriate use and interpretation of activity and damage indices, comparable remission and response criteria and stratification of high risk populations have been the subject of much discussion and emerging consensus. As long-term outcomes in lupus improve, the toxicity of therapy and risk of relapse become increasingly important determinants of choice of therapeutic agents.
Lupus 2006
PMID:Mycophenylate mofetil: what role in the treatment of lupus? 1663 73

Mycophenolate mofetil (MMF) significantly reduces proteinuria in experimental model of human membranous nephropathy (Heymann nephritis). Twenty consecutive SLE patients with persistent isolated severe proteinuria and/or proteinuric flare were studied for 18 months of MMF therapy. All of them presented stable renal function and 12 had biopsy proven membranous glomerulonephritis (WHO class V). The starting daily dose for MMF was 1.5 g to a maximum of 3 g. Patients were divided into: partial response, >or=50% decrease of baseline proteinuria; complete response, normal proteinuria levels (less than 0.3 g/24 h); flare, increase of at least 50% of the mean baseline proteinuria. All 20 SLE patients (100%) presented a 50% reduction of baseline proteinuria which was achieved in 8.2+/-3.3 months of MMF therapy, at a mean daily dose of 2.3+/-0.5 g. A significant decrease in 24-h protein excretion was observed compared to entry (3.47+/-1.26 vs. 1.33+/-0.67 g, P<0.0001) as well as a correspondent increase of serum albumin (3.2+/-0.4 vs. 3.7+/-0.4 mg/dl, P=0.02) and reduction of prednisone dose (33.7+/-20.0 to 18.6+/-14.1 mg/day, P=0.01). Complete response was observed in 11 SLE patients (55%) in 12.2+/-3.0 months of therapy with a significant decrease in proteinuria (P<0.0001), prednisone dose (P<0.0001) and an increase of serum albumin (P=0.003). Interestingly, initial proteinuria or serum albumin levels did not identify patients with complete response and those with partial response at the end of the study (P=0.543 and 0.657, respectively). Our pilot prospective study suggests that MMF appears to be effective in reducing severe persistent proteinuria in lupus glomerulonephritis, even in patients unresponsive to other immunosuppressive treatments.
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PMID:Mycophenolate mofetil is effective in reducing lupus glomerulonephritis proteinuria. 1673 62

Systemic lupus erythematosus, which predominantly affects young women, frequently is complicated by renal involvement. The presence of acute glomerulonephritis significantly adds to morbidity and mortality. Based on currently published clinical trials, induction therapy with cyclophosphamide combined with pulse corticosteroids is an efficacious treatment option to preserve renal function, and long-term data are available to support this choice. Mycophenolate mofetil is a promising new agent, and recent data suggest that it is at least as efficacious as cyclophosphamide in the induction and maintenance phase, but with fewer side effects. Cell-depleting agents may be added in patients who fail the traditional regimens, preferentially in the setting of one of the ongoing clinical trials. The number of treatment regimens that the clinician can choose from when confronted with a patient with severe lupus nephritis has increased significantly, and more options are on the horizon. This promises more efficacious and better tolerable therapies, but it also puts an additional obligation on the physician to consider risk-to-benefit ratio, patient preference and adherence, feasibility, and cost; and to engage the patient in an active discussion about the different alternatives.
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PMID:New directions in the management of severe lupus nephritis. 1676 Aug 82

Mycophenolate mofetil (MMF) is an immunosuppressant drug being used for induction and maintenance of remission of lupus nephritis in systemic lupus erythematosus. Evidence about its use was sought from full publications and abstracts of randomised trials and cohort studies by using a variety of search strategies. Efficacy and adverse event outcomes were sought. Five randomised trials enrolled patients with World Health Organization (WHO) class III, IV, or V (mostly IV) lupus nephritis, predominantly comparing MMF (1 to 3 g daily) with cyclophosphamide and steroid. Complete response and complete or partial response was significantly more frequent with MMF than with cyclophosphamide, with numbers needed to treat of 8 (95% confidence interval 4.3 to 60) to induce one additional complete or partial response, with wide confidence intervals. Death was reported less frequently with MMF (0.7%, 1 death in 152 patients) than with cyclophosphamide (7.8%, 12 deaths in 154 patients), with a number needed to treat to prevent (NNTp) one death of 14 (8 to 48). Hospital admission was also lower with MMF (1.7% versus 15%; NNTp 7.4 [4.8 to 16]). Serious infections, leucopaenia, amenorrhoea, and hair loss were all significantly less frequent with MMF than with cyclophosphamide, but diarrhoea was significantly more common with MMF. Ten of 18 cohort studies enrolled only patients with lupus nephritis (author-defined or WHO class III to V). Seven of these 10 reported that complete or partial response with MMF (mostly 1 or 2 g daily) with steroid occurred in 121/151 (80%) and that treatment failure or no response occurred in 30/151 (20%). Adverse events were generally similar in cohort studies with and without only patients with lupus nephritis. In all 18 cohorts, gastrointestinal adverse events (diarrhoea, nausea, vomiting) occurred in 30%, infection in 23%, and serious infection in 4.3%. Adverse event discontinuations occurred in 14% and lack of efficacy occurred in 10%. There was a single death with MMF, a mortality rate over the course of 1 year of approximately 0.2%. The results form a basis on which to plan future studies and provide a guide for the use of MMF in lupus nephritis until results of larger studies are available. At least one such study is under way.
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PMID:Systematic review and meta-analysis of randomised trials and cohort studies of mycophenolate mofetil in lupus nephritis. 1716 90

According to the NIH scheme, the "evidence based medicine" standard in the treatment of severe proliferative lupus-nephritis is cyclophosphamide in combination with steroids. Undesired effects, therapy resistance, and deficient long-term effects underscore the necessity for the development of alternative therapies for the treatment of organ involvement. Mycophenolate mofetil (MMF) possesses the potential to decisively improve the therapeutic possibilities for systemic lupus erythematosus (SLE). On the basis of the available data, MMF represents an alternative to the current standard therapies for severe lupus-nephritises and shows less toxicity. MMF is also effective in patients with other manifestations refractory to conventional therapy. Questions remain unanswered on the optimal dosage and possible reduction in cases of remission. In addition, the duration of maintenance therapy is unclear. Therefore, large, prospective, randomized clinical studies in the treatment of lupus-nephritis with a sufficiently long follow-up phase are underway.
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PMID:[Revision of the recommendations of the Commission on Pharmacotherapy of the German Society for Rheumatology. Comment on the use of mycophenolic acid for systemic lupus erythematosus]. 1721 18

Mycophenolate mofetil (MMF) is a new immunosuppressant recently introduced in the treatment of autoimmune conditions. The greatest experience with the use of MMF has been achieved in the treatment of proliferative lupus glomerulonephritis. However, MMF has also been used to control SLE extra-renal manifestations as well as other autoimmune rheumatic diseases such as idiopathic inflammatory arthropathies, inflammatory myopathies, systemic sclerosis, and systemic vasculitis. MMF seems to be well tolerated and effective and could be considered a useful alternative to standard immunosuppressants for the treatment of autoimmune rheumatic disorders. However, further studies are needed in order to determine its real place in the treatment of these conditions. In this paper, the use of MMF in different autoimmune rheumatic diseases is reviewed and discussed.
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PMID:Mycophenolate mofetil: what is its place in the treatment of autoimmune rheumatic diseases? 1728 56

Mycophenolate mofetil (MMF) is an immunosuppressive agent initially used in the treatment of transplant recipients. MMF has been used in renal, heart, and liver transplantation, where it seems more effective than other immunosuppressive regimens in reducing the incidence of acute rejection episodes. MMF has a variety of immunosuppressive effects, including selective suppression of T and B lymphocyte proliferation, and has been more recently used in many autoimmune inflammatory conditions. Systemic lupus erythematosus (SLE) is an autoimmune disease that can potentially involve any organ or system of the human body. Glomerulonephritis (GLN) has been recognized as the most frequent severe manifestation of SLE, leading to poor long-term prognosis. In the treatment of lupus GLN, several therapeutic approaches, all including immunosuppressive drugs, such as cyclophosphamide, azathioprine, or cyclosporine A, have been used. The short- and long-term toxicity of these drugs limits their use in a substantial number of patients. Over the last few years, MMF has emerged as an alternative therapeutic regimen in lupus GLN, mainly for patients refractory to other therapies. These studies have shown that it is highly effective and generally well tolerated.
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PMID:Mycophenolate mofetil in lupus glomerulonephritis: effectiveness and tolerability. 1791 67

Studies of immunosuppressive therapy, particularly mycophenolate mofetil (MMF), in membranous lupus nephritis (MLN) are limited. We report on our experience with primary (first-line) MMF therapy to induce and sustain renal remission in MLN with and without a concurrent proliferative lesion. Systemic lupus erythematosus (SLE) patients were studied, retrospectively, if treated with MMF for newly diagnosed MLN. Complete remission was defined as proteinuria less than 0.5 g/24 h, inactive urine sediment and normal estimated glomerular filtration rate. Response in pure MLN (Group I, n=10) was compared with mixed MLN and proliferative lupus nephritis (Group II, n=19). By 12 months, 4 (40%) patients in Group I and 7 (36.8%) in Group II achieved complete remission (P=0.87). One (10%) patient in Group I and 2 (10.5%) in Group II had worsening renal disease (P=0.97). Mean time to remission was more than seven months in both groups. The remaining patients had stable disease without improvement or worsening. Only 2 of 11 achieving initial remission had a relapse with an average of 28 months of follow-up after remission. Self-limited gastrointestinal symptoms occurred in 12 patients, none requiring withdrawal of the drug. Mycophenolate mofetil as a primary therapy in MLN was successful in inducing complete remission in about 40% of MLN, particularly in patients with mild proteinuria. However, 12 months of therapy was necessary for best outcomes. Response rate was not different in the presence or absence of a proliferative lesion.
Lupus 2008 Jan
PMID:Mycophenolate mofetil as the primary treatment of membranous lupus nephritis with and without concurrent proliferative disease: a retrospective study of 29 cases. 1808 82

Mycophenolate mofetil has been shown to have teratogenic properties in animal studies and clinical reports. We report a case of major fetal malformation likely caused by mycophenolate mofetil exposure in utero in a 36 year old patient with systemic lupus erythematosus. The diagnosis was made by ultrasonography at 22 weeks of gestation.
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PMID:Sonographic diagnosis of fetal malformations associated with mycophenolate mofetil exposure in utero. 1848 91

Mycophenolate mofetil (MMF) with prednisolone has been associated with high remission rates when used as induction treatment for lupus nephritis. This prospective, multicentre, cohort study investigates the efficacy and safety of this regimen over 24 weeks in 213 Chinese patients with active lupus nephritis (Classes III, IV, V or combination). Baseline activity index (AI) was 6.91+/-3.33 and chronicity index (CI) was 1.9+/-1.2. The remission rate was 82.6% at 24 weeks (complete remission, 34.3%; partial remission, 48.4%). There were significant (P<0.01) improvements in kidney function shown by reductions in proteinuria, serum albumin, serum creatinine and creatinine clearance, as well as in systemic lupus erythematosus disease activity index (SLEDAI) scores. Independent risk factors influencing remission were pathological classification (including Class V and III or Class V and IV nephritis) and elevated serum creatinine at baseline (OR 2.967, 95% CI: 1.479-6.332, P=0.001 and OR 1.007, 95% CI: 1.002-1.011, P=0.001, respectively). Patients with concomitant membranous features on biopsy had a lower remission rate than those with Class III and IV nephritis (66.7% vs 87.3%, P=0.002). Renal biopsy was repeated in 25 patients following treatment. There was a transition to less severe pathological morphologies in majority of subjects. Infections were monitored throughout treatment: eight patients (3.8%) experienced bacterial infections, whereas herpes zoster occurred in seven patients. Nine patients (4.2%) suffered from gastrointestinal upset, which resolved without discontinuation of MMF. One patient became leucopenic, whereas another died from active disease unrelated to kidney symptoms. MMF combined with prednisolone is an effective and well-tolerated induction treatment for patients with active lupus nephritis and for controlling SLE systemic activity.
Lupus 2008 Jul
PMID:A prospective multicentre study of mycophenolate mofetil combined with prednisolone as induction therapy in 213 patients with active lupus nephritis. 1862 34


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