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Rituximab for Remission Induction and Maintenance in Refractory Systemic Lupus Erythematosus  [PDF]
Fabio Bonilla-Abadía,Nicolás Coronel Restrepo,Gabriel J. Tobón,Andrés F. Echeverri,Evelyn Mu?oz-Buitrón,Andres Mauricio Castro,Mercedes Andrade Bejarano,Carlos A. Ca?as
Autoimmune Diseases , 2014, DOI: 10.1155/2014/731806
Abstract: Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease with high morbidity if untreated. Sometimes, despite aggressive treatments, the disease remains active with cumulative organic damage. We conducted a retrospective and descriptive observational study of patients with SLE refractory to conventional treatment who were treated with rituximab (RTX) as remission induction therapy and maintenance. There was a significant reduction in the conventional immunosuppressive drug dose and the number of relapses of disease. RTX appeared to be effective and safe for the induction and maintenance of remission in patient with SLE refractory to conventional treatment. 1. Introduction Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease with no permanent cure or high morbidity if left untreated [1]. Sometimes, despite aggressive treatments with high dose of glucocorticoids and immunosuppressive drugs, the disease remains active with cumulative organic damage [2]. The disease severity appears to be higher in Hispanics compared to Caucasians. Thus, the overall survival rates vary by race and ethnic background with a 5-year survival rate of approximately 95% among whites, 90% among blacks, and 87% among Hispanics [3]. The management of patients with SLE depends on the type of organ involvement and severity of the disease. When manifestations are severe, with threatening life conditions, the treatment is based on high-dose steroids, plasmapheresis, intravenous gamma globulin, and various types of immunosuppressants such as cyclophosphamide, azathioprine, or mofetil mycophenolate [4]. Some patients remain with active disease despite full immunosuppressive drugs. Two monoclonal antibodies targeting B cells have been used successfully in refractory SLE: belimumab directed against B-cell activating factor (BAFF) [5] and Rituximab which is a genetically engineered chimeric anti-CD20 monoclonal antibody. CD20 is a B-cell surface antigen that is expressed only on pre-B and mature B cells. It is not present on stem cells and is lost before differentiation of B cells into plasma cells. Therefore, rituximab causes a selective transient depletion of the CD20+ B-cell subpopulation [6]. Rituximab (RTX) is currently approved for the management of B-cell lymphomas, rheumatoid arthritis (RA) and systemic vasculitis ANCA (antineutrophil cytoplasmic antibodies) positive [7, 8], and it is used as a single dose for SLE crisis with varying results [9–11]. There are few reports in the literature about routine and chronic use of RTX as a
Uso del rituximab(anticuerpo monoclonal anti-CD20) en lupus eritematoso sistémico refractario a tratamiento: Caso clínico Rituximab (anti-CD20 monoclonal antibody) for refractory systemic lupus erythematosus: Report of one case  [cached]
Francisca Sabugo S,Carolina Llanos M,Lilian Soto S,Jorge Gutiérrez
Revista médica de Chile , 2005,
Abstract: New therapeutic approaches that include depletion of B cells using rituximab, a chimeric monoclonal antibody directed against the B cell specific antigen CD-20 have been developed for the treatment of systemic lupus erythematosus (SLE). We report the case of a 18 years old girl with SLE that did not respond and experienced adverse effects with the use of hydroxycloroquine, methotrexate, mycophenolate mofetil, azathioprine and high-dose steroids. Rituximab was given weekly at 375 mg/m2 for four doses. The drug was well tolerated and the patient had no adverse reactions. She remains asymptomatic three months later
Response to rituximab in a refractory case of thrombotic thrombocytopenic purpura associated with systemic lupus erythematosus  [cached]
Niaz Faraz,Aleem Aamer
Saudi Journal of Kidney Diseases and Transplantation , 2010,
Abstract: Thrombotic thrombocytopenic purpura (TTP) is a serious disorder with a significant morbidity and mortality. Majority of cases of TTP are idiopathic, but some cases may be secon-dary to connective tissue diseases. TTP has been rarely associated with systemic lupus erythe-matosus (SLE) and may be refractory to treatment with plasma exchange, requiring immuno-suppressive therapy. We describe a patient with TTP and SLE who was refractory to plasma exchange and corticosteroids but responded to anti-CD20 antibody rituximab with continued re-mission after eight months of follow-up. Rituximab appears to be an effective treatment in re-fractory cases of TTP associated with SLE.
B-cell targeted therapy in systemic lupus erythematosus: potential of rituximab
Wiesik-Szewczyk E,Olesinska M
Biologics: Targets and Therapy , 2012,
Abstract: E Wiesik-Szewczyk, M OlesinskaInstitute of Rheumatology, Department of Connective Tissue Diseases, Warsaw, PolandAbstract: Systemic lupus erythematosus (SLE) is a complex autoimmune disease of unknown etiology, and the limited available therapeutic options for this disease, are frustrating to both clinicians and patients. However, recent advances in the understanding of disease mechanisms have given rise to numerous studies on specific approaches to SLE treatment. Rituximab, the first chimeric, mouse-human monoclonal antibody which is directed against CD20, seems to be a new therapeutic option. The purpose of this review is to explain the current clinical evidence on the therapeutic use of rituximab in adult SLE patients. Two randomized clinical trials with rituximab (the EXPLORER and LUNAR studies) failed to prove efficacy of this drug on SLE. Ongoing data analysis continues to explain the reasons behind why this treatment fails to work. However data from open source and observational studies contrast with clinical trials results. The global analysis of this data supports the off-label use of rituximab in subsets of SLE that are refractory to standard treatment.Keywords: B cells, systemic lupus erythematosus, rituximab, off-label use, clinical trials
B-cell targeted therapy in systemic lupus erythematosus: potential of rituximab
Wiesik-Szewczyk E, Olesinska M
Biologics: Targets and Therapy , 2012, DOI: http://dx.doi.org/10.2147/BTT.S25407
Abstract: -cell targeted therapy in systemic lupus erythematosus: potential of rituximab Review (2077) Total Article Views Authors: Wiesik-Szewczyk E, Olesinska M Published Date September 2012 Volume 2012:6 Pages 347 - 354 DOI: http://dx.doi.org/10.2147/BTT.S25407 Received: 08 May 2012 Accepted: 21 July 2012 Published: 26 September 2012 E Wiesik-Szewczyk, M Olesinska Institute of Rheumatology, Department of Connective Tissue Diseases, Warsaw, Poland Abstract: Systemic lupus erythematosus (SLE) is a complex autoimmune disease of unknown etiology, and the limited available therapeutic options for this disease, are frustrating to both clinicians and patients. However, recent advances in the understanding of disease mechanisms have given rise to numerous studies on specific approaches to SLE treatment. Rituximab, the first chimeric, mouse-human monoclonal antibody which is directed against CD20, seems to be a new therapeutic option. The purpose of this review is to explain the current clinical evidence on the therapeutic use of rituximab in adult SLE patients. Two randomized clinical trials with rituximab (the EXPLORER and LUNAR studies) failed to prove efficacy of this drug on SLE. Ongoing data analysis continues to explain the reasons behind why this treatment fails to work. However data from open source and observational studies contrast with clinical trials results. The global analysis of this data supports the off-label use of rituximab in subsets of SLE that are refractory to standard treatment.
Rituximab for refractory granulomatous eye disease
Lower EE, Baughman RP, Kaufman AH
Clinical Ophthalmology , 2012, DOI: http://dx.doi.org/10.2147/OPTH.S35521
Abstract: uximab for refractory granulomatous eye disease Case Series (1139) Total Article Views Authors: Lower EE, Baughman RP, Kaufman AH Published Date October 2012 Volume 2012:6 Pages 1613 - 1618 DOI: http://dx.doi.org/10.2147/OPTH.S35521 Received: 01 July 2012 Accepted: 11 August 2012 Published: 05 October 2012 Elyse E Lower1,2 Robert P Baughman,1 Adam H Kaufman3 1Department of Medicine, University of Cincinnati Medical Center, Cincinnati, OH, USA; 2Oncology Hematology Care, Cincinnati, OH, USA; 3Department of Ophthalmology, University of Cincinnati, Cincinnati, OH, USA Objective: To determine the effectiveness of rituximab therapy for patients with granulomatous disease of the eye. Methods: Retrospective review was undertaken of cases seen at a single institution for ocular antineutrophil cytoplasmic antibody-associated vasculitis or sarcoidosis with persistent ocular disease despite systemic therapy. All patients were treated with rituximab and followed for at least 6 months. Results: Nine patients were identified (five with antineutrophil cytoplasmic antibody-associated vasculitis, four with sarcoidosis), and all were treated for at least 6 months. Eight experienced improvement of eye disease and were able to reduce prednisone and other drug therapies. One patient remained stable, but still required high dosages of prednisone. All five patients with lung disease improved with rituximab therapy. Rituximab treatment was well tolerated. Two patients discontinued the drug due to leukopenia; however, both patients reinstituted rituximab at modified doses. Conclusion: Rituximab therapy was effective in controlling granulomatous ocular disease in most cases. The drug was corticosteroid-sparing and effective in refractory cases, with no severe adverse events encountered.
Rituximab for refractory granulomatous eye disease  [cached]
Lower EE,Baughman RP,Kaufman AH
Clinical Ophthalmology , 2012,
Abstract: Elyse E Lower1,2 Robert P Baughman,1 Adam H Kaufman31Department of Medicine, University of Cincinnati Medical Center, Cincinnati, OH, USA; 2Oncology Hematology Care, Cincinnati, OH, USA; 3Department of Ophthalmology, University of Cincinnati, Cincinnati, OH, USAObjective: To determine the effectiveness of rituximab therapy for patients with granulomatous disease of the eye.Methods: Retrospective review was undertaken of cases seen at a single institution for ocular antineutrophil cytoplasmic antibody-associated vasculitis or sarcoidosis with persistent ocular disease despite systemic therapy. All patients were treated with rituximab and followed for at least 6 months.Results: Nine patients were identified (five with antineutrophil cytoplasmic antibody-associated vasculitis, four with sarcoidosis), and all were treated for at least 6 months. Eight experienced improvement of eye disease and were able to reduce prednisone and other drug therapies. One patient remained stable, but still required high dosages of prednisone. All five patients with lung disease improved with rituximab therapy. Rituximab treatment was well tolerated. Two patients discontinued the drug due to leukopenia; however, both patients reinstituted rituximab at modified doses.Conclusion: Rituximab therapy was effective in controlling granulomatous ocular disease in most cases. The drug was corticosteroid-sparing and effective in refractory cases, with no severe adverse events encountered.Keywords: sarcoidosis, wegener’s, ANCA, cyclophosphamide
A Case of Subacute Cutaneous Lupus Erythematosus in a Patient with Mixed Connective Tissue Disease: Successful Treatment with Plasmapheresis and Rituximab  [PDF]
M. Fantò,S. Salemi,F. Socciarelli,A. Bartolazzi,G. A. Natale,I. Casorelli,A. Pavan,S. Vaglio,R. Di Rosa,R. D'Amelio
Case Reports in Rheumatology , 2013, DOI: 10.1155/2013/857694
Abstract: A 30-year-old woman affected by Mixed Connective Tissue Disease with scleroderma spectrum developed a facial eruption, a clinical and histological characteristic of subacute cutaneous lupus erythematosus (SCLE). Speckled anti-nuclear antibodies, high-titer anti-ribonucleoprotein1, anti-Sm, anti-Cardiolipin (aCL) IgG/IgM, and anti-Ro/SSA antibodies were positive. SCLE was resistant to Azathioprine, Hydroxychloroquine, and Methotrexate while Mycophenolate Mofetil was suspended due to side effects. Subsequently, the patient was treated with three cycles of therapeutic plasma exchange (TPE) followed, one month after the last TPE, by the anti-CD20 antibody Rituximab (RTX) (375?mg/m2 weekly for 4 weeks). Eight and 16 months later the patient received other two TPE and RTX cycles, respectively. This therapeutic approach has allowed to obtain a complete skin healing persistent even after 8-month follow-up. Moreover, mitigation of Raynaud's phenomenon, resolution of alopecia, and a decline of aCL IgG/IgM and anti-Ro/SSA antibodies were observed. 1. Introduction Mixed Connective Tissue Disease (MCTD) is currently defined as an overlapping syndrome with clinical features of Systemic Sclerosis (SSc), Systemic Lupus Erythematosus (SLE), Rheumatoid arthritis (RA), and Polymyositis/Dermatomyositis (PM/DM); the presence of high-titer anti-ribonucleoprotein1 (U1RNP) or speckled anti-nuclear antibodies (ANA) at titer ≥1?:?2,000 is necessary for the diagnosis. The disease affects mainly women in the third decade of life (from 80 to 90%) but it has been also reported in children and in over-80-year-old people [1]. The most frequent clinical manifestations are Raynaud's phenomenon (RP), swollen hands, sclerodactyly, arthritis, myalgias, and oesophageal dysmotility, and also alopecia, malar rash, lymphadenopathy, or kidney damage can be present. Rarely, subacute cutaneous lupus erythematosus (SCLE), characterized by annular or papulosquamous lesions, photosensitivity, and presence of anti-Ro/SSA and anti-La/SSB antibodies, has been described in MCTD patients [2, 3]. MCTD therapy should be identified for each patient depending on the affected organ, but generally there is a good response to steroids, different types of vasodilators, and immunosuppressive agents such as Hydroxychloroquine (HCQ), Azathioprine (AZA), Methotrexate (MTX), or Cyclophosphamide (CYC) [1]. 2. Case Presentation A case of a thirty-year-old woman affected by MCTD with scleroderma spectrum and epilepsy since she was fifteen is here reported. At the beginning she presented fever up to 40°C, arthalgias
Differential effects on BAFF and APRIL levels in rituximab-treated patients with systemic lupus erythematosus and rheumatoid arthritis
Therese Vallerskog, Mikael Heimbürger, Iva Gunnarsson, Wei Zhou, Marie Wahren-Herlenius, Christina Trollmo, Vivianne Malmstr?m
Arthritis Research & Therapy , 2006, DOI: 10.1186/ar2076
Abstract: Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are chronic inflammatory rheumatic diseases, in which autoantibodies are part of the early disease manifestations. A pathogenic involvement of B cells is well documented in SLE and implicated in RA. Rituximab is a chimeric monoclonal antibody that depletes B cells by targeting CD20, a surface molecule expressed exclusively on B cells. After rituximab infusion, circulating B cells are rapidly depleted and remain absent for months. Although originally developed to treat B-cell lymphomas, it has also been used successfully in various autoimmune diseases, including SLE and RA (reviewed by Eisenberg [1]).Recently, two closely related cytokines that belong to the tumour necrosis factor (TNF) family and that are important for B-cell development and function were described: BAFF (B-cell activation factor of the TNF family, BlyS, THANK, TALL-1, TNFSF13b, zTNF-4) and APRIL (a proliferation-inducing ligand, TNFSF13a) [2]. They share two receptors, BCMA (B-cell maturation antigen) and TACI (transmembrane activator and CAML [calcium-modulating cyclophilin ligand] interactor), which are found mainly on B cells and plasma cells (reviewed by Ng and colleagues [3] and Schneider [4]). The third receptor specific for BAFF, BAFF-R (BAFF receptor, BR3), is found mainly on B cells, plasma cells, but also on some subsets of T cells [3,4]. So far, APRIL has no specific receptor of its own, but it has been shown to bind proteoglycans [5]. With the above receptors expressed mainly on B cells, these cells are the major consumers of these cytokines.BAFF is produced constitutively by stromal cells within lymphoid organs [6] and is inducible by cells of myeloid origin (monocytes, macrophages, neutrophils, and dendritic cells) and also by osteoclasts (reviewed by Ng and colleagues [3] and Dillon and colleagues [7]). APRIL is produced mainly by the same cells as BAFF [3,7]. It was recently demonstrated that some B cells also produce
Use of Rituximab in Refractory Dermatomyositis: A Case Report  [PDF]
K. Grover, R. Peshin
Open Journal of Rheumatology and Autoimmune Diseases (OJRA) , 2013, DOI: 10.4236/ojra.2013.31006
Abstract:

We report a case of a 56-year-old female with a confirmed diagnosis of Dermatomyositis on muscle biopsy, which was refractory to 5 different disease modifying drugs as well as intravenous immunoglobulins and symptoms improved dramatically with a single course of Rituximab. We hereby wish to highlight the importance of Rituximab in this highly resistant case and that anti CD 20 biologic drugs can be considered as standard treatment protocol in refractory Dermatomyositis.

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