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Isenberg and rituximab

Pedro L Carreira, David A Isenberg
SLE has a complex pathogenesis, and multiple therapeutic targets have been discovered in recent years. In spite of belimumab being approved by the US Food and Drug Administration and the widespread use of rituximab, there have been many failed attempts to treat SLE successfully using biologic agents. In this review, we consider newer biologic approaches that might offer the hope of improving the outcome of SLE patients. These include the fully humanized anti-CD20 mAbs, PEGylated anti-CD40L, IFNα inhibitors, rigerimod and immune complexes blockade...
April 5, 2018: Rheumatology
André R Alexandre, Pedro L Carreira, David A Isenberg
Lupus nephritis (LN) affects up to 50% of patients with Systemic Lupus Erythematosus (SLE) and is associated with a worse prognosis. LN usually develops within the first 5 years of the onset of the disease. We report three patients with very delayed LN (DLN) diagnosed after 15 or more years after SLE diagnosis. The three patients were non-Caucasian women with adolescent or adult-onset SLE. Each had antinuclear, anti-dsDNA and anti-Ro antibodies. Hydroxychloroquine was prescribed for each. Their disease courses were characterised by sporadic non-renal flares controlled by steroids and, in two cases, by one cycle of rituximab...
2018: Lupus Science & Medicine
Eoghan M McCarthy, Emily Sutton, Stephanie Nesbit, James White, Ben Parker, David Jayne, Bridget Griffiths, David A Isenberg, Anisur Rahman, Caroline Gordon, David P D'Cruz, Benjamin Rhodes, Peter Lanyon, Edward M Vital, Chee-Seng Yee, Christopher J Edwards, Lee-Suan Teh, Mohammed Akil, Neil J McHugh, Asad Zoma, Ian N Bruce
Objectives: To describe the baseline characteristics of SLE patients requiring biologic therapy in the UK and to explore short term efficacy and infection rates associated with rituximab (RTX) use. Methods: Patients commencing biologic therapy for refractory SLE and who consented to join BILAG-BR were analysed. Baseline characteristics, disease activity (BILAG 2004/SLEDAI-2K) and rates of infection over follow-up were analysed. Response was defined as loss of all A and B BILAG scores to ⩽ 1 B score with no new A/B scores in other organ systems at 6 months...
March 1, 2018: Rheumatology
Eoghan M McCarthy, Emily Sutton, Stephanie Nesbit, Ben Parker, David Jayne, Bridget Griffiths, David A Isenberg, Anisur Rahman, Caroline Gordon, David P D'Cruz, Benjamin Rhodes, Peter Lanyon, Edward M Vital, Chee-Seng Yee, Christopher J Edwards, Lee-Suan Teh, Mohammed Akil, Neil J McHugh, Asad Zoma, Ian N Bruce
No abstract text is available yet for this article.
June 1, 2017: Rheumatology
Eoghan M McCarthy, Emily Sutton, Stephanie Nesbit, Ben Parker, David Jayne, Bridget Griffiths, David A Isenberg, Anisur Rahman, Caroline Gordon, David P D'Cruz, Benjamin Rhodes, Peter Lanyon, Edward M Vital, Chee-Seng Yee, Christopher J Edwards, Lee-Suan Teh, Mohammed Akil, Neil J McHugh, Asad Zoma, Ian N Bruce
No abstract text is available yet for this article.
June 1, 2017: Rheumatology
Venkat Reddy, Christian Klein, David A Isenberg, Martin J Glennie, Geraldine Cambridge, Mark S Cragg, Maria J Leandro
Objective: A proportion of RA and SLE patients treated with standard doses of rituximab (RTX) display inefficient B cell deletion and poor clinical responses that can be augmented by delivering higher doses, indicating that standard-dose RTX is a sub-optimal therapy in these patients. This study aimed to investigate whether better responses could be achieved with mechanistically different anti-CD20 mAbs. Methods: We compared RTX with obinutuzumab (OBZ), a new-generation, glycoengineered type II anti-CD20 mAb, in a series of in vitro assays measuring B cell cytotoxicity in RA and SLE patient samples...
July 1, 2017: Rheumatology
Borja Gracia-Tello, Amara Ezeonyeji, David Isenberg
BACKGROUND: Previous reports indicate that treating patients with lupus (SLE) at or close to the time of diagnosis successfully without using any, or minimal, corticosteroids by using B-cell depletion (BCD) is possible in the short-term. It is not however known whether using BCD is as effective or reduces corticosteroid use in the long-term. We report the long-term (up to 7 years) use of BCD with respect to its steroid-saving capacity and clinical effectiveness in newly diagnosed SLE...
2017: Lupus Science & Medicine
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 followup...
June 2017: 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...
January 2017: Rheumatology
R Aguiar, C Araújo, G Martins-Coelho, D Isenberg
OBJECTIVE: To describe the clinical outcome and safety of rituximab (RTX) treatment in systemic lupus erythematosus (SLE) patients with severe manifestations or whose disease is 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 1 center between June 2000 and December 2013. The clinical outcome was assessed by determining British Isles Lupus Assessment Group (BILAG) scores and anti-double-stranded DNA (anti-dsDNA) and C3 levels before and 6 months after RTX treatment...
February 2017: 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...
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
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