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)

Mycophenolate mofetil (MMF) has proved to be an efficacious and safe therapy in adult lupus nephritis. Recently, this drug has been suggested as a possible new alternative treatment also for juvenile-onset SLE (juvenile-SLE). A multicenter study has been performed to evaluate the efficacy and safety of MMF in controlling the disease activity in children and adolescents with juvenile-SLE. Our results show that MMF was effective in reducing the disease activity or as a steroid-sparing agent in 14 of 26 patients (54%), stabilised the disease in 8 (31%) and was ineffective in 4 (15%). In particular, in patients without renal involvement, a good response was registered in 9 of 13 patients (69%). Among those patients with renal involvement, MMF was effective in 5 of 13 patients (38%), partially effective in 4 (31%) and ineffective in 4 (31%). No severe side effects have been observed; only two patients stopped the drug because of severe diarrhoea and abdominal pain. With the limits of a retrospective study, MMF seems to be effective and safe for the treatment of juvenile-SLE, especially in patients with no renal involvement.
Lupus 2009 Feb
PMID:Mycophenolate mofetil for the treatment of juvenile onset SLE: a multicenter study. 1915 Nov 15

Mycophenolate mofetil (MMF) is effective in the treatment of patients with active systemic lupus erythematosus (SLE). We sought to evaluate its efficacy in reducing the number of disease flares in adults with SLE. For this retrospective study, all patients seen at our institution over a six year period, 1999-2005, with the diagnosis of SLE treated with MMD were identified. Data regarding lupus flare was obtained for patients at least one and up to two years prior to starting MMF. The number of flares prior to MMF therapy was compared to the number of lupus flares in the one to two year period after starting MMF. Clinical assessment was performed with the SELENA-SLEDAI instrument. Differences between groups were compared using the signed rank test. The rate of flares (flares per person-year), before and after the introduction of MMF were compared assuming the occurrence of flares followed a Poisson distribution. In the evaluable 67 patients, the mean time period of followup prior to starting MMF was 14.1 months (range 0.3-24), mean time period of follow-up after starting MMF was 14.8 months (range 1.5-24); and mean MMF dose was 1328 mg/day (range 250-3000). The mean flare rate was reduced from 8.9 to 5.3 per 10 personyears and the mean prednisone dose was reduced on average 7.3 mg/day after starting MMF therapy. MMF treatment significantly reduced the total number of lupus flares and prednisone requirements. Even with the reduction in mean daily prednisone dose, both the SLEDAI and physican global assessment also improved during MMF therapy.
Lupus 2009 Apr
PMID:Mycophenolate mofetil is effective in reducing disease flares in systemic lupus erythematosus patients: a retrospective study. 1931 90

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of unknown etiology with multisystem involvement. A number of pulmonary complications including pleuritis, pneumonitis, infectious pneumonia, and pulmonary hemorrhage, have been reported in patients with SLE. Pulmonary hemorrhage is a major life-threatening manifestation in children and adolescents with SLE. Mycophenolate mofetil is an immunosuppressive agent used in solid organ transplantation, and it may play an increasing role in autoimmune disease. In this report, we present two cases of childhood SLE with recurrent pulmonary hemorrhage, which were unresponsive to treatment with high-dose corticosteroids, cytotoxic therapy, IVIG, plasmaphoresis, and supportive therapy, but responded to IV mycophenolate mofetil. A multimodal therapy including mycophenolate mofetil was effective in treatment of these two children.
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PMID:Treatment of intractable pulmonary hemorrhage in two patients with childhood systemic lupus erythematosus. 1935 Feb 42

Lupus nephritis is a complication of systemic lupus erythematosus, which has significant morbidity and mortality. The accepted standard of treatment for severe lupus nephritis is cyclophosphamide for induction of remission. This has significant adverse effects including severe infection and amenorrhea. In addition, although cyclophosphamide induces remission, long-term mortality does not seem to be altered. Mycophenolate mofetil (MMF) is an immunosuppressive agent originally used in solid organ transplantation, which has been compared with cyclophosphamide in trials for lupus nephritis. Randomized trials with MMF have been relatively small, although pooled data seem to suggest that it is at least as effective as cyclophosphamide in inducing remission. In addition, MMF has also been associated with a reduced risk of infection and amenorrhea, although this finding is not universal. MMF appears to be associated with more diarrhea compared with cyclophosphamide. MMF is likely to be a useful treatment for lupus nephritis, although available trial data are limited due to the small size of previous studies. A large trial (the Aspreva Lupus Management Study) is currently underway to attempt to establish the place of MMF in treatment of lupus nephritis.
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PMID:Mycophenolate mofetil in the treatment of lupus nephritis. 1970 62

Generation of oxidative stress induced by reactive oxygen species (ROS) and nitrogen (RNS) is believed to be a primary factor in the etiology of various inflammatory diseases. Although, the process of generation of oxygen species is a physiological event, in the inflammatory process this event is increased and produces large amounts of reactive species that leads to lipid peroxidation and to cell death. Mycophenolate mofetil (MMF) is a drug effective in protecting against chronic allograft failure and recently was introduced as an alternative for the treatment of various inflammatory diseases such as glomerulopathies, systemic lupus erythematosus and systemic vasculitis. Based on studies of the anti-inflammatory effect of MMF the aim of this study was to evaluate the effects of MMF on the inhibition of leukocytes and exudation, as well as myeloperoxidase and some antioxidant enzyme activities using carrageenan-induced pleurisy in mice. Our results showed that MMF significantly decreased leukocyte influx (P<0.01), exudation (P<0.01), superoxide dismutase (P<0.05), catalase (P<0.05), glutathione peroxidase (P<0.01), glutathione S-transferase (P<0.01) activities, levels of lipid peroxidation (P<0.05), as well as myeloperoxidase activity (P<0.05) on both phases (4h and 48h) of the inflammatory response induced by carrageenan into the mice pleural cavity. In conclusion, the anti-inflammatory effect of MMF may be, at least in part, via inhibition of ROS and/or NRS overgeneration, and consequently, attenuating the related oxidative stress.
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PMID:Antioxidant effects of mycophenolate mofetil in a murine pleurisy model. 1977 12

Mycophenolic acid (MPA) is a potent, selective, noncompetitive and reversible inhibitor of inosine-5'-monophosphate deshydrogenase (IMPDH). By depleting guanosine and deoxyguanosine nucleotides in T and B lymphocytes it inhibits their proliferation and, hence, immunoglobin (Ig) production. MPA also suppresses dendritic cell maturation decreasing its capacity of antigen presentation to T lymphocytes. MPA reduces the recruitment of monocytes into sites of graft rejection and inflammation. Mycophenolate mofetil (MMF) is a prodrug of MPA that was developed to improve the bioavailability of MPA. After oral administration, MMF is completely metabolized to MPA. A major inactive metabolite, mycophenolic acid glucuronide (MPAG), is formed after MPA glucuronidation. MPAG has an important role in the enterohepatic recirculation of MPA. MMF is approved for the prophylaxis of allograft rejection after renal, cardiac or liver transplant. The oral dose ranges from 1.0-1.5 g/day twice daily. Moreover, studies on the use of MMF in lung and simultaneous pancreas/ kidney transplants have shown encouraging results. MMF also demonstrates potential in the treatment of autoimmune diseases such as lupus, myasthenia gravis and glomerular disorders. This review focuses on the molecular mechanism of action and pharmacological characteristics of MPA. Studies in both approved and nonapproved applications are also summarized.
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PMID:Mycophenolate mofetil: An update. 1983 29

Mycophenolate mofetil (MMF) has recently been introduced as an immunosuppressive agent for the treatment of glomerulonephritis with systemic lupus erythematosus (SLE) and the data have been encouraging. However, response to MMF treatment appears to differ ethnically. Therefore, we determined efficacy and safety of low-dose MMF for Taiwanese patients with lupus nephritis. We studied 36 lupus nephritis patients who were treated with MMF. The dose started at 0.5 g/day and we collected the data from patients who received up to 1 g/day MMF. Outcome measures were 24 h for proteinuria, serum creatinine, C3/C4 levels, and anti-dsDNA titers collected at the baseline and at 3-month treatment intervals. Daily urinary protein significantly decreased from 6.15 +/- 4.28 g to 2.69 +/- 2.36 g at the last visit (P < 0.01) in spite of the significant absence of changes in serum creatinine levels. The response rate was 65.7% including five (14.3%) cases of complete remission and 18 (51.4%) cases of partial remission. The concomitant oral prednisolone dose decreased significantly from 20.07 +/- 11.78 mg/day to 13.93 +/- 6.79 mg/day at 6 months (P < 0.01). The level of C3 increased significantly from 59.46 +/- 32.73 to 71.99 +/- 25.81 (P < 0.01) and the anti-dsDNA antibody titer decreased from 161.71 +/- 221.42 to 46.57 +/- 117.47 (P < 0.01). No severe adverse effects were observed in the study. Low-dose MMF (0.5 to 1 g/day) combined with glucocorticoids appears to be a safe and effective therapy for lupus nephritis in Taiwanese patients. Our results suggest that lupus nephritis in Oriental patients might respond to lower doses of MMF than Caucasians.
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PMID:The efficacy of low-dose mycophenolate mofetil for treatment of lupus nephritis in Taiwanese patients with systemic lupus erythematosus. 2019 79

Approved treatment options for moderate-to-severe systemic lupus erythematosus (SLE) and lupus nephritis (LN) are presently very limited. Mycophenolate mofetil (MMF), an immunosuppressive agent indicated for acute transplant rejection prophylaxis, has been increasingly used to treat these conditions. The best evidence-based information on the use of MMF in SLE comes from studies of LN. Randomized, controlled trials of MMF have been conducted only in this subset of lupus patients. The data suggest that the drug is well tolerated, effective and should be considered a useful alternative to standard immunosuppressants for the treatment of LN. The aim of this article is to examine the available evidence concerning MMF in lupus and LN.
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PMID:Mycophenolate mofetil for lupus nephritis. 2047 21

This review covers the major advances in the therapeutic potentials related to systemic lupus erythematosus published in Medline between 2000 and February 2005. Controlled, open and Phase I-III trials were included. Anecdotal reports were excluded. Several trials have defined the role of cyclophosphamide, methotrexate, antimalarials, hormonal treatment and mycophenolate mofetil (Cellcept) in the management of systemic lupus erythematosus. The aims of novel biologics for systemic lupus erythematosus are to target the autoimmune disease at different points: B-cell depletion (rituximab [Rituxan], anti-BLys antibodies [Lymphostat-B]), inhibition of T-B interaction (rituximab), blockade of cytokines (anti-interleukin-10 antibodies), manipulation of idiotypes (intravenous immunoglobulin), tolerance induction to DNA and immunoglobulin-peptides and peptide therapy (abetimus sodium [Riquent]). Low-dose intravenous cyclophosphamide (Euro-Lupus protocol) is as effective as the conventional National Institutes of Health protocol and is also associated with less toxicity. Stem cell transplantation for severe disease induces remission in most patients, however, the relapse rate in a third of patients and the associated morbity and mortality restricts its use to selected patients with life-threatening disease. Intravenous immunoglobulin, although utilized in open trials, is effective and safe for various manifestations of systemic lupus erythematosus. Major advances have been associated with mycophenolate mofetil and rituximab. Mycophenolate mofetil is effective for induction and maintenance therapy of lupus proliferative glomerulonephritis and is associated with fewer adverse events than monthly intravenous cyclophosphamide. Rituximab is a promising agent, and although its utilization is presently limited, it appears to be effective for lupus patients with severe disease.
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PMID:Novel approaches to therapy for systemic lupus erythematosus: update 2005. 2047 36

Neurological manifestations in lupus can be due to active lupus disease affecting the brain or to other reasons. Reversible posterior leucoencephalopathy syndrome, primary lymphoma of the central nervous system, cerebral infections by bacteria (e.g. mycobacteria), viruses (e.g. JC virus), fungi (e.g. Cryptococcus) and parasites (e.g. Acanthamoeba), steroid-induced psychosis and reactive depression need to be excluded. Brain-reactive autoantibodies have been described as associating with neuropsychiatric lupus. The strongest associations described to date are with antiribosomal P protein and antiphospholipid antibodies. However these autoantibodies have not been shown to play significant roles in the pathogenesis. Treatment strategy for severe neuropsychiatric lupus include establishing definitive diagnosis, early identification and treatment of aggravating factors, appropriate symptomatic treatment, adequate immunosuppression, selective B-cell depletion and autologous haematopoietic stem cell transplant. Systematic reviews have shown that cyclophosphamide administration is superior to pulse methylprednisolone as a maintenance therapy. Mycophenolate mofetil has been shown to have modest effect and should only be considered if cyclophosphamide cannot be administered.
Lupus 2010 Oct
PMID:Neuropsychiatric lupus: clinical challenges, brain-reactive autoantibodies and treatment strategies. 2094 48


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