Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Systemic lupus erythematosus (SLE) is a chronic, inflammatory autoimmune disease that may involve multiple organ systems. Treatment consists of immunosuppression, cytotoxic treatment, plasmapheresis and immunoglobuline therapy. Treatment of patients refractory to standard treatment approaches is difficult and results are poor. We describe a 39-year old patient with SLE suffering from grand mal epilepsy due to cerebral vasculopathy with positive lupus anticoagulant, who was refractory to standard treatment modalities. The patient was treated with the anti-CD20 monoclonal antibody rituximab (375 mg/m2 x 4, repeated at weekly intervals). Rituximab applications were delivered in October 2000, March 2001 and October 2001. Since March 2002 she has received maintenance therapy with rituximab 375 mg/m2 every three months. A second female with refractory SLE was treated successfully in April 2002 and receives maintenance therapy every three months. Both patients responded well to rituximab therapy. The first patient showed a major improvement of her clinical condition, and 30 months after the beginning of the rituximab therapy she is free of any symptoms. Inflammation parameters, ANA and lupus anticoagulant declined significantly after the treatment. The clinical condition of the second patient improved dramatically, all inflammation parameters normalized and her circulating immunocomplexes disappeared. In conclusion, rituximab maintenance treatment may be a new effective therapy in SLE.
Lupus 2003
PMID:Successful long-term treatment of systemic lupus erythematosus with rituximab maintenance therapy. 1459 28

Rituximab, a chimeric monoclonal CD20 antibody, is useful in the treatment of B-cell lymphomas and certain autoimmune diseases. We report a successful outcome of rituximab for life threatening hypercoagulable state associated with lupus anticoagulant (LA). A 30-year-old woman initially presented 10 years ago with DVT and positive serology for SLE and LA. While on Coumadin, she suffered from recurrent DVT in the legs and arms, pulmonary emboli, Budd-Chiari syndrome, mesenteric vein thrombosis, bone infarcts, recurrent strokes, and chronic ITP. All measures including plasmapheresis and monthly IV cyclophosphamide were of no benefit. She was recently admitted with spontaneous subdural hematoma with INR of 3.8. Upon discontinuation of anticoagulation for surgical drainage, she developed acute abdomen from thrombosis and recurrent DVT. Because she had failed prior standard measures, 4 weekly infusions of rituximab (375 mg/m2) were given following 2 rounds of plasmapheresis. Subsequently, she made a remarkable recovery over the next month and has been free of thrombosis on Coumadin for over 15 months. LA, IgM antibodies to cardiolipin, and B2GP1 were consistently positive. After rituximab therapy, LA became negative and IgM antibodies to cardiolipin decreased and ITP went into remission. Rituximab induced a lasting remission in a woman suffering from life-threatening hypercoagulable state associated with LA. Her clinical remission was associated with disappearance of LA.
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PMID:Long-term remission from life-threatening hypercoagulable state associated with lupus anticoagulant (LA) following rituximab therapy. 1568 9

The use of B cell depletion as a mode of treatment for non-Hodgkin's lymphoma was first utilized in 1997 when Rituximab, a chimeric human-mouse monoclonal antibody which has a high affinity to the CD20 antigen expressed on B cells, became available. Over 500000 lymphoma patients have been treated worldwide with this drug and it has a good safety record. The notion that B cells might be critical to the development of rheumatoid arthritis led to the extension of the use of B cell depletion to this condition and a recent double blind controlled trial has shown very encouraging results. In addition, B cell depletion either using Rituximab alone, or in combination with cyclophosphamide and corticosteroids has also been reported to have been of great benefit in some patients with severe systemic lupus erythematosus albeit in open label studies. This review considers the mechanism of action of the drug, the clinical trials that have been reported, and tries to place its current use in patients with autoimmune rheumatic disease in context.
Lupus 2005
PMID:Anti-B cell therapy (rituximab) in the treatment of autoimmune diseases. 1580 98

We studied the clinical and immunological effects of Rituximab (anti-CD20) therapy in patients with lupus nephritis. In an open clinical trial, 22 patients with active systemic lupus erythematosis and renal involvement (mainly class III and IV according to the WHO classification) that was refractory to conventional therapy were studied. In all these patients, Rituximab (0.5 to 1.0 g at days 1 and 15) was added to the immunosuppressive therapy and its therapeutic effect was evaluated. In addition, the levels and function of regulatory T lymphocytes and the apoptosis of immune cells were assessed. We found a significant reduction in disease activity (p < 0.05, MEX-SLEDAI index), and proteinuria (p < 0.05) at days 60 and 90 of Rituximab therapy. Although most patients showed improvement in creatinine clearance and erythrocyturia, no significant changes in these parameters were detected. In most patients (20/22), B cell depletion was observed, but no clear-cut effect of Rituximab on complement levels or auto-antibody titers was detected (p > 0.05 in all cases). One patient died at day 70 with invasive histoplasmosis. No important adverse effects of Rituximab therapy were registered in other patients. A significant enhancement in the levels of different CD4+ regulatory cells (TREG, Th3, Tr1), but not CD8+ Ts lymphocytes, was observed at day 30. This increase was sustained for TREG cells at day 90, and accompanied by an improvement in their regulatory function. In addition, we observed an unexpected increase in the apoptosis of T cells at day 30. Interestingly, the enhancement in the suppressive function of TREG cells was not observed in the two patients that showed the poorest clinical response to Rituximab. We conclude that the data obtained in this open clinical trial suggest that Rituximab is a promising candidate for randomized controlled trials in patients with lupus nephritis refractory to the conventional immunosuppressive therapy. The effects of Rituximab on regulatory cells and apoptosis of T lymphocytes are interesting and its possible role in the putative effect of this biological agent in systemic lupus erythematosis deserves additional studies.
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PMID:Clinical and immunological effects of Rituximab in patients with lupus nephritis refractory to conventional therapy: a pilot study. 1667 95

The aim of this study was to evaluate the response to treatment and the long-term outcome in a cohort of patients in whom severe autoimmune hemolytic anaemia (AHA) was the leading manifestation of systemic lupus erythematosus (SLE). Twenty-six women with severe isolated AHA were included. Corticosteroids were used as the initial treatment for all patients in our study. An initial response was obtained in all but one patient (96%). The overall recurrence rate was three per 100 person-years, with an expected recurrence-free proportion of 73% with a 180 months median follow-up. Seven patients (27%) experienced a relapse of AHA. We found a higher proportion of pleuritis in relapsing patients. Only three patients experienced multiple relapses despite splenectomy and several immunosuppressants. Steroid-sparing effect of hydroxychloroquine and azathioprine could not be assessed because most of the patients received these treatments for other reasons than AHA. Intravenous immunoglobulins induced transient response in three cases. Splenectomy was efficient to definitively control AHA in one patient but two patients quickly experienced relapses while one patient did not benefit. Five patients received immunosuppressants that induced only transient responses. Rituximab was long-term efficient in one case. In conclusion, severe AHA is a serious complication of SLE that warrants appropriate management. On the basis of our experience, the ideal treatment of isolated AHA should be oral corticosteroids in first-line treatment. Our study does not support an important role for splenectomy. Patients refractory to conventional therapy should be treated either with few toxic immunosuppressive drugs, danazol or rituximab.
Lupus 2006
PMID:Treatment of isolated severe immune hemolytic anaemia associated with systemic lupus erythematosus: 26 cases. 1668 62

After many barren years, conceptual advances and the introduction of new biotherapies are yielding improvements in the management of systemic lupus erythematosus (SLE). The result is a radical change in the management strategy. The main therapeutic advances rest on new discoveries (or rediscoveries), some of which are original. They can be summarized under 12 headlines. Smoking is inadvisable, as it promotes not only atheroma but also lupus flares. Hydroxychloroquine and conventional drugs (cyclophosphamide) are helpful provided they are used appropriately. Combined oral contraception and hormone replacement therapy may be less hazardous than previously thought, although caution remains in order. Drugs used in transplant recipients, such as mycophenolic acid, are generating optimism as treatments for SLE. Rituximab and new anti-B-cell drugs hold promise for the treatment of severe SLE. Efforts to develop an "etiologic" treatment for SLE based on type 1 (alpha/beta) interferon blockade still face a number of obstacles. Peptide vaccines, whose main effect is stimulation of regulator T cells, hold promise-but confirmation is needed. Whether TNF antagonists can be used in lupus with skin and joint manifestations or in SLE is generating debate. Complement blockade for treating SLE and antiphospholipid syndrome is an attractive avenue of research. Numerous new immunotherapy modalities based on modulating intracellular signaling are being evaluated. In the most severe forms of SLE, autologous peripheral stem cell transplantation deserves consideration. A key component of the treatment of SLE is control of atheroma, which is among the most severe complications. This rich harvest of new treatment possibilities can be expected to radically modify the prognosis of SLE, whose more aggressive forms remain severe.
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PMID:Treatment of systemic lupus erythematosus in 2006. 1711 Jan 51

The European League Against Rheumatism (EULAR)'s guidelines for lupus state that mycophenolate mofetil has at least equivalent efficacy to and less toxicity than cyclophosphamide for the short-and medium-term treatment of lupus nephritis but that long-term data are available only for cyclophosphamide. New therapies are needed to reduce toxicity and the need for steroids and to offer the possibility of cure. Therapies under investigation include other immunosuppressive agents, anti-cellular therapies, drugs that modify cell-cell interactions, (anti-)cytokine therapy, hormone therapy and lupus-specific immunomodulation. Rituximab has shown promise in patients refractory to conventional immunosuppression, which suggests that targeting B cells may be successful. Other anti-cell therapies include epratuzumab, belimumab and alemtuzumab. Anti-cytokine approaches include tumour necrosis factor alpha blockade with infliximab, anti-interleukin 6-receptor therapy with tocilizumab and interferon-alpha blockade. As antidouble-stranded DNA antibodies correlate with flares of lupus nephritis, they may represent another therapeutic target--as do monocyte chemoattractant protein-1 and protein kinase CK2. Therapeutic options to prevent damage in lupus nephritis include non-immunosuppressive treatments aimed at reducing cardiovascular risk (such as statins, angiotensin-converting enzyme inhibitors and aspirin). As was the case with rheumatoid arthritis, a change in therapeutic aims--from survival through prevention of renal failure to induction of remission--may modify outcomes. EULAR's guidelines state that renal biopsy is the best monitor of clinical outcome in lupus nephritis, as immunological tests have limited predictive value. Measurement of urinary mRNA for cytokine and growth factor genes may provide a more sensitive, non-invasive method of monitoring therapeutic response.
Lupus 2007
PMID:Exploring new territory: considering the future. 1743 11

The main goal of therapy for lupus nephritis is to achieve remission, as this has a major impact on patient and renal survival. Furthermore, early treatment success has been shown to improve long-term prognosis. This has traditionally been achieved with intravenous cyclophosphamide, but recent data show that mycophenolate mofetil is equally effective and causes fewer adverse effects. Research is ongoing to find new treatment targets. Possible future therapies include monoclonal antibodies against CD20 (rituximab), CD22 (epratuzumab) and CD40, and therapies targeted at cytokine secretion, immunoglobulin secretion, B-cell maturation and T-cell proliferation and differentiation. Rituximab has shown promise in patients with active proliferative lupus nephritis, which suggests that B-cell depletion may be successful. Anti-double-stranded DNA antibodies correlate with flares of lupus nephritis and may represent another therapeutic target. Therapy with LIP 394, which crosslinks anti-double-stranded DNA antibodies in solution or on the B-cell surface, has been shown to reduce flares. Cardiovascular disease is a major cause of mortality in systemic lupus erythematosus, and this must also be addressed if long-term outcomes are to be improved. Many patients with systemic lupus erythematosus have subclinical atherosclerosis quite early in the disease course, and the risk of coronary artery disease at any level of traditional cardiovascular risk factors is higher than in the general population. Specific lupus-associated risk factors include the inflammatory process itself and anticardiolipin antibodies. Possible strategies to reduce the risk include reduction of disease activity to improve endothelial function and reduction of steroid dose whenever possible. Therapy with aspirin or statins may be another possibility. Thus treatment of lupus nephritis is evolving from standardised therapy to individualised therapy based on analysis of organ involvement, risk factors and cytokine, antibody or cell profiles.
Lupus 2007
PMID:Exploring new territory: the move towards individualised treatment. 1743 12

Although corticosteroids and immunosuppressants are widely used for the treatments of systemic lupus erythematosus (SLE), safer and more effective therapies are prerequisite. We and others have reported that anti-CD20 antibody rituximab targeting B cells are effective for refractory SLE and, therefore, safety and clinical efficacy of rituximab in SLE was evaluated by a multicenter phase I/II clinical trial. An open-label, multicenter study of 15 patients with active and refractory SLE (total British Isles Lupus Assessment Group [BILAG] score 8 to 17) was conducted. Rituximab was administered to 5 SLE patients as 4 infusions of 500 mg/body every week and to 10 SLE patients as 2 infusions of 1000 mg/body every other week. Assessment of safety, infusion reactions and adverse effects was used as the primary outcome for clinical tolerability and was evaluated by 28 weeks. Rituximab was well tolerated, with most experiencing no significant adverse effects. B cells rapidly reduced in all patients and remained low until 6 months post-treatment. Four patients developed human antichimeric antibodies without affecting efficacy of rituximab. Changes in routine safety laboratory tests clearly related to rituximab were not observed. Nine among 14 evaluable patients achieved the major or partial clinical response of BILAG score and prednisolone dose significantly decreased at the 28 weeks. Rituximab therapy appears to be safe for the treatment of active SLE patients and holds significant therapeutic promise, at least for the majority of patients experiencing profound B-cell depletion.
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PMID:A multicenter phase I/II trial of rituximab for refractory systemic lupus erythematosus. 1756 73

We report a 47-year-old female with Sjogren's syndrome (SS) and severe weakness in her lower extremities refractory to cyclophosphamide therapy, who was treated with the monoclonal anti CD-20 antibody rituximab at a weekly dose of 375 mg/m2 for four consecutive weeks. Patient responded within few days of the first dose and her motor power in the lower extremities started to improve gradually along with progressive resolution of the paresthesias and dysesthesias. The improvement was sustained and progressive and eight months after the last dose, she was able to walk for 60 meters without aid or rest. Rituximab may be considered as an effective and promising novel therapy in SS patients with neurological involvement.
Lupus 2007
PMID:Successful treatment of refractory neuroSjogren with Rituximab. 1767 Aug 52


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