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Isenberg and rituximab

Monica Rydén-Aulin, Dimitrios Boumpas, Irene Bultink, Jose Luis Callejas Rubio, Luis Caminal-Montero, Antoni Castro, Agustín Colodro Ruiz, Andrea Doria, Thomas Dörner, Cristina Gonzalez-Echavarri, Elisa Gremese, Frederic A Houssiau, Tom Huizinga, Murat Inanç, David Isenberg, Annamaria Iuliano, Søren Jacobsen, Juan Jimenéz-Alonso, Lászlo Kovács, Xavier Mariette, Marta Mosca, Ola Nived, Joaquim Oristrell, Manuel Ramos-Casals, Javier Rascón, Guillermo Ruiz-Irastorza, Luis Sáez-Comet, Gonzalo Salvador Cervelló, Gian Domenico Sebastiani, Danilo Squatrito, Gabriella Szücs, Alexandre Voskuyl, Ronald van Vollenhoven
OBJECTIVES: Rituximab (RTX) is a biological treatment used off-label in patients with systemic lupus erythematosus (SLE). This survey aimed to investigate the off-label use of RTX in Europe and compare the characteristics of patients receiving RTX with those receiving conventional therapy. METHODS: Data on patients with SLE receiving RTX were taken from the International Registry for Biologics in SLE retrospective registry and complemented with data on patients with SLE treated with conventional therapy...
2016: Lupus Science & Medicine
Venkat Reddy, Lina Martinez, David A Isenberg, Maria J Leandro, Geraldine Cambridge
OBJECTIVE: B cell depletion therapy based on rituximab is a therapeutic option for refractory disease in patients with Systemic Lupus Erythematosus (SLE). The aim of this observational study was to document long-term effects on B cell function by following serum immunoglobulin levels in patients with SLE treated with rituximab in routine clinical practice. METHODS: We included 57 consecutive patients with SLE treated with rituximab and concomitant/sequential immunosuppressants and measured serum total IgG, IgM, and IgA and IgG anti-dsDNA antibodies over a median of 48 months most recent follow-up...
July 18, 2016: Arthritis Care & Research
Serena Fasano, Patrick Gordon, Raouf Hajji, Esthela Loyo, David A Isenberg
Several uncontrolled studies have encouraged the use of rituximab (RTX) in patients with myositis. Unfortunately, the first placebo-phase trial to assess the efficacy of RTX in refractory myositis did not show a significant difference between the two treatment groups, and doubts have been expressed about its study design. In this review we present an up-to-date overview of the reported experiences of RTX therapy in myositis. A PubMed search was performed to find all the available cases of refractory myositis patients treated with RTX up to July 2015...
April 27, 2016: Rheumatology
R Aguiar, C Araújo, G Martins-Coelho, D Isenberg
OBJECTIVES: To describe the clinical outcome and safety of rituximab (RTX) treatment in systemic lupus erythematosus (SLE) patients with severe manifestations or refractory to standard immunosuppressive therapy, treated at a single center. METHODS: This was a retrospective analysis of all patients with SLE treated with RTX at one center between June 2000 and December 2013. The clinical outcome was assessed by determining BILAG scores, anti dsDNA and C3 levels before and six months after RTX treatment...
April 25, 2016: Arthritis Care & Research
Madhvi Menon, Paul A Blair, David A Isenberg, Claudia Mauri
Signals controlling the generation of regulatory B (Breg) cells remain ill-defined. Here we report an "auto"-regulatory feedback mechanism between plasmacytoid dendritic cells (pDCs) and Breg cells. In healthy individuals, pDCs drive the differentiation of CD19(+)CD24(hi)CD38(hi) (immature) B cells into IL-10-producing CD24(+)CD38(hi) Breg cells and plasmablasts, via the release of IFN-α and CD40 engagement. CD24(+)CD38(hi) Breg cells conversely restrained IFN-α production by pDCs via IL-10 release. In systemic lupus erythematosus (SLE), this cross-talk was compromised; pDCs promoted plasmablast differentiation but failed to induce Breg cells...
March 15, 2016: Immunity
Serena Fasano, Sara Custódio Alves, David A Isenberg
The idiopathic inflammatory myopathies are uncommon and heterogeneous disorders. Their classification is based on distinct clinicopathologic features. Although idiopathic inflammatory myopathies share some similarities, different subtypes may have variable responses to therapy, so it is very important to distinguish the correct subtype. There are few randomised, double blind placebo controlled studies to support the current treatment. High dose corticosteroids continue to be the first-line therapy and other immunosupressive drugs are used in refractory cases, as well as steroid-sparing agents...
February 6, 2016: Expert Review of Clinical Pharmacology
Clare Oni, Sheryl Mitchell, Katherine James, Wan-Fai Ng, Bridget Griffiths, Victoria Hindmarsh, Elizabeth Price, Colin T Pease, Paul Emery, Peter Lanyon, Adrian Jones, Michele Bombardieri, Nurhan Sutcliffe, Costantino Pitzalis, John Hunter, Monica Gupta, John McLaren, Annie Cooper, Marian Regan, Ian Giles, David Isenberg, Vadivelu Saravanan, David Coady, Bhaskar Dasgupta, Neil McHugh, Steven Young-Min, Robert Moots, Nagui Gendi, Mohammed Akil, Francesca Barone, Ben Fisher, Saaeha Rauz, Andrea Richards, Simon J Bowman
OBJECTIVE: To identify numbers of participants in the UK Primary Sjögren's Syndrome Registry (UKPSSR) who would fulfil eligibility criteria for previous/current or potential clinical trials in primary SS (pSS) in order to optimize recruitment. METHODS: We did a retrospective analysis of UKPSSR cohort data of 688 participants who had pSS with evaluable data. RESULTS: In relation to previous/current trials, 75.2% fulfilled eligibility for the Belimumab in Subjects with Primary Sjögren's Syndrome study (Belimumab), 41...
March 2016: Rheumatology
Venkat Reddy, Geraldine Cambridge, David A Isenberg, Martin J Glennie, Mark S Cragg, Maria Leandro
OBJECTIVE: Rituximab, a type I anti-CD20 monoclonal antibody (mAb), induces incomplete B cell depletion in some patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), thus contributing to a poor clinical response. The mechanisms of this resistance remain elusive. The purpose of this study was to determine whether type II mAb are more efficient than type I mAb at depleting B cells from RA and SLE patients, whether internalization influences the efficiency of depletion, and whether Fcγ receptor type IIb (FcγRIIb) and the B cell receptor regulate this internalization process...
May 2015: Arthritis & Rheumatology
Pablo Ruiz Sada, David Isenberg, Coziana Ciurtin
SS is a chronic systemic autoimmune disease characterized by decreased exocrine gland function. A variety of other disease manifestations may also be present, including general constitutional symptoms and extraglandular features. A multidisciplinary approach focused on both local and systemic medical therapies is needed as the disease has a wide clinical spectrum. The current treatment for SS is mainly symptomatic. However, there is evidence that systemic drugs are effective in controlling extraglandular manifestations of the disease...
February 2015: Rheumatology
Venkat Reddy, Gabriel Martin Garcia, David Isenberg, Maria Leandro, Geraldine Cambridge
BACKGROUND AND AIMS: In vitro, BAFF (B-lymphocyte activating factor) differentially promotes the survival of B-cells and plasmablasts through receptors for the key B-cell cytokine BAFF. Following rituximab (RTX) therapy in patients with systemic lupus erythematosus (SLE), serum BAFF levels increase. The aim was to determine the effect of RTX treatment on relationships amongst BAFF, B-cell sub-populations and receptors for BAFF (BAFF-R). MATERIALS AND METHODS: Twenty-three RTX-naïve (RTX-N) and 12 RTX-treated (RTX-T) SLE patients and six healthy controls (HCs) were included...
March 1, 2014: Annals of the Rheumatic Diseases
Venkat Reddy, Lina Martinez, David Isenberg, Geraldine Cambridge, Maria Leandro
BACKGROUND AND AIMS: The impact of rituximab therapy on different compartments of the immune system may inform as to the possible clinical response and also maintenance of protective immunity. We conducted a retrospective study of serum IgM, IgG and IgA in 59 patients with SLE, following the first cycle of B cell depletion therapy based on rituximab (RTX). MATERIALS AND METHODS: Serum Ig levels (IgA, IgG and IgM) were assessed at baseline (before first infusion of RTX) and at 1, 2, 6, 9 and 12 months after the first cycle of RTX in 59 patients with SLE...
March 1, 2014: Annals of the Rheumatic Diseases
A L Taborda, P Azevedo, D A Isenberg
OBJECTIVES: Several factors have been implicated in the prognosis of idiopathic inflammatory myopathies, including age, gender, delay in diagnosis, neoplasia, creatine kinase levels and some autoantibodies. We have reviewed the main factors contributing to mortality in patients with idiopathic inflammatory myopathy (IIM) diagnosed between 1976 and 2007 who were followed for at least 5 years in the Rheumatology Unit at University College Hospital in London. METHODS: An observational retrospective study was carried out on patients with IIM diagnosed between 1976 and 2007...
March 2014: Clinical and Experimental Rheumatology
Zozik Fattah, David A Isenberg
INTRODUCTION: Major trials hoping to obtain optimal disease control in systemic lupus erythematosus (SLE) are ongoing. Given its complex aetiology and pathogenesis, it is not surprising that multiple therapeutic targets have emerged and that none are uniformly successful. AREAS COVERED: In this review, we highlight the recent, more significant studies focusing on the use of biologic therapies. There has been great emphasis on the role of B cells in SLE and many uncontrolled studies have encouraged the use of rituximab (an anti-CD20 monoclonal)...
March 2014: Expert Opinion on Biological Therapy
Francisco Muñoz-Beamud, David A Isenberg
OBJECTIVES: To assess the efficacy and safety of B-lymphocyte depletion therapy (BCDT) utilising rituximab in refractory idiopathic inflammatory myositis. METHODS: We retrospectively evaluated 16 adult patients with active dermatomyositis (DM) or polymyositis (PM) who received 1 gram rituximab intravenous infusions two weeks apart after failing to respond to conventional therapy. The clinical and biochemical response were analysed by the Myositis Intention to Treat index (MITAX) and the serum creatine kinase (CK) levels at baseline and 6 and 12 months after treatment...
November 2013: Clinical and Experimental Rheumatology
S C Hofmann, M J Leandro, S D Morris, D A Isenberg
Cutaneous manifestations occur frequently in systemic lupus erythematosus (SLE) and are pathognomonic in subacute-cutaneous lupus erythematosus (SCLE) and chronic cutaneous lupus erythematosus (CCLE). Although B-cell depletion therapy (BCDT) has demonstrated efficacy in SLE with visceral involvement, its usefulness for patients with predominant skin manifestations has not been fully established. In this single-centre, retrospective study 14 consecutive SLE, one CCLE and two SCLE patients with recalcitrant skin involvement were treated with 2 × rituximab 1 g, and 1 × cyclophosphamide 750 mg...
August 2013: Lupus
Lucy M Carter, David A Isenberg, Michael R Ehrenstein
OBJECTIVE: To determine whether serum BAFF levels correlate with relapse or remission in patients with systemic lupus erythematosus (SLE) following B cell depletion therapy (BCDT) and to assess the relationship between serum BAFF levels, B cell numbers, and immunoglobulin and autoantibody levels during active disease, both before and after BCDT. METHODS: Thirty-five patients with active SLE underwent BCDT with rituximab and were monitored for a minimum of 18 months, using clinical and serologic measures of disease activity...
October 2013: Arthritis and Rheumatism
Venkat Reddy, David Jayne, David Close, David Isenberg
B cells are believed to be central to the disease process in systemic lupus erythematosus (SLE), making them a target for new therapeutic intervention. In recent years there have been many publications regarding the experience in SLE of B-cell depletion utilising rituximab, an anti-CD20 mAb that temporarily depletes B cells,reporting promising results in uncontrolled open studies and in routine clinical use. However, the two large randomised controlled trials in extra-renal lupus (EXPLORER study) and lupus nephritis (LUNAR study) failed to achieve their primary endpoints...
2013: Arthritis Research & Therapy
George K Bertsias, Maria Tektonidou, Zahir Amoura, Martin Aringer, Ingeborg Bajema, Jo H M Berden, John Boletis, Ricard Cervera, Thomas Dörner, Andrea Doria, Franco Ferrario, Jürgen Floege, Frederic A Houssiau, John P A Ioannidis, David A Isenberg, Cees G M Kallenberg, Liz Lightstone, Stephen D Marks, Alberto Martini, Gabriela Moroni, Irmgard Neumann, Manuel Praga, Matthias Schneider, Argyre Starra, Vladimir Tesar, Carlos Vasconcelos, Ronald F van Vollenhoven, Helena Zakharova, Marion Haubitz, Caroline Gordon, David Jayne, Dimitrios T Boumpas
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)...
November 2012: Annals of the Rheumatic Diseases
David A Isenberg
B cell depletion (BCD) has become established in the treatment of patients with rheumatoid arthritis (RA) vasculitis and systemic lupus erythematosus (SLE). However, although successfully confirmed to be useful in major large scale trials in RA and vasculitis, two SLE trials did not meet their endpoints. Given the widespread use of BCD in SLE it seems likely that it will continue to be used though better designed trials (which work) would help resolve on-going problems with regulatory and funding agencies.
September 2012: Autoimmunity Reviews
Mark N Lazarus, Tabitha Turner-Stokes, Konstantia-Maria Chavele, David A Isenberg, Michael R Ehrenstein
OBJECTIVES: To correlate the kinetics of B-cell repopulation with relapse after B-cell depletion therapy in SLE patients and address whether variation in relapse rate, B-cell numbers and phenotype are related to anti-dsDNA antibody levels. METHODS: Sixty-one patients with refractory SLE were treated with a standard rituximab regimen. Clinical and serological measures of disease activity and B-cell numbers were assessed. B-cell phenotype was examined in a subgroup of patients by flow cytometry...
July 2012: Rheumatology
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