keyword
https://read.qxmd.com/read/38321569/where-are-we-now-in-biological-drugs-for-myositis
#1
JOURNAL ARTICLE
Ana Neves, Luísa Viveiros, Veronica Venturelli, David A Isenberg
Idiopathic inflammatory myopathies (IIM) are a rare and heterogeneous group of chronic autoimmune disorders. Up to 40% of IIM patients have long-term sequelae and significant functional disability. Its management can be challenging. New therapies are badly needed. The small number of cases with diverse presentations, and different diagnostic criteria interfere significantly with clinical trial results. Only intravenous immunoglobulin has been internationally approved for IIM patients. Most clinical trials of new biological therapies have failed to meet their primary endpoints in IIM, with only one biological drug recommended for refractory IIM treatment (rituximab), although not approved...
February 6, 2024: Rheumatology
https://read.qxmd.com/read/37336639/approach-to-vaccination-in-systemic-lupus-erythematosus-on-biological-treatment
#2
REVIEW
Reşit Yıldırım, Tatiana Oliveira, David Alan Isenberg
In recent years, treat-to-target strategy and early intervention strategies with immunosuppressive agents have attempted to improve the prognosis and outcome in patients with autoimmune inflammatory rheumatic diseases. However, infectious complications due to side effects of medication remain a major concern in routine practice. In this regard, vaccine immunity and vaccination programmes are of the utmost importance in patients with systemic lupus erythematosus (SLE) in terms of morbidity and mortality. Encouragingly, research investigations have increased exponentially, both in monitoring the vaccines efficacy, and in determining the immune response while patients are on immunosuppression...
September 2023: Annals of the Rheumatic Diseases
https://read.qxmd.com/read/36756239/identification-of-biomarkers-to-stratify-response-to-b-cell-targeted-therapies-in-systemic-lupus-erythematosus-an-exploratory-analysis-of-a-randomised-controlled-trial
#3
JOURNAL ARTICLE
Muhammad Shipa, Liliana R Santos, Dao X Nguyen, Andrew Embleton-Thirsk, Mariea Parvaz, Lauren L Heptinstall, Ruth J Pepper, David A Isenberg, Caroline Gordon, Michael R Ehrenstein
BACKGROUND: Systemic lupus erythematosus (SLE) is a complex autoimmune disease associated with widespread immune dysregulation and diverse clinical features. Immune abnormalities might be differentially associated with specific organ involvement or response to targeted therapies. We aimed to identify biomarkers of response to belimumab after rituximab to facilitate a personalised approach to therapy. METHODS: In this exploratory analysis of a randomised controlled trial (BEAT-LUPUS), we investigated immune profiles of patients with SLE recruited to the 52-week clinical trial, which tested the combination of rituximab plus belimumab versus rituximab plus placebo...
January 2023: Lancet Rheumatology
https://read.qxmd.com/read/36622027/rituximab-in-myositis-where-are-we-now-a-survey-of-current-usage
#4
JOURNAL ARTICLE
Tatiana Oliveira, Reşit Yıldırım, Claire Deakin, David Isenberg
No abstract text is available yet for this article.
July 5, 2023: Rheumatology
https://read.qxmd.com/read/36370065/anti-rituximab-antibodies-demonstrate-neutralising-capacity-associate-with-lower-circulating-drug-levels-and-earlier-relapse-in-lupus
#5
JOURNAL ARTICLE
Chris Wincup, Nicky Dunn, Caroline Ruetsch-Chelli, Ali Manouchehrinia, Nastya Kharlamova, Meena Naja, Barbara Seitz-Polski, David A Isenberg, Anna Fogdell-Hahn, Coziana Ciurtin, Elizabeth C Jury
OBJECTIVES: High rates of anti-drug antibodies (ADA) to rituximab have been demonstrated in patients undergoing treatment for systemic lupus erythematosus (SLE). However, little is known with regards to their long-term dynamics, impact on drug kinetics and subsequent implications for treatment response. In this study, we aimed to evaluate ADA persistence over time, impact on circulating drug levels, assess clinical outcomes and whether they are capable of neutralising rituximab. METHODS: Patients with SLE undergoing treatment with rituximab were recruited to this study (n = 35)...
November 12, 2022: Rheumatology
https://read.qxmd.com/read/35809059/adverse-events-of-treatment-with-rituximab-in-patients-with-myositis
#6
LETTER
Sergio Gilaberte, Joana Rua, David Isenberg
No abstract text is available yet for this article.
February 1, 2023: Rheumatology
https://read.qxmd.com/read/35652065/differences-in-the-development-of-adverse-infusion-reactions-to-rituximab-in-patients-with-systemic-lupus-erythematosus-rheumatoid-arthritis-and-non-hodgkin-s-lymphoma-enigma-variations
#7
REVIEW
Sergio Gilaberte Reyzabal, David Isenberg
It has become clear that rituximab treatment is useful for both B-cell malignancies and autoimmune rheumatic diseases. However this treatment is associated with an increased risk of an allergic reaction. We have reviewed the frequency with which these reactions occur in these different conditions. They appear to be less frequent when rituximab is used to treat rheumatoid arthritis and systemic lupus perhaps because concomitant steroids are invariably given to these patients with the rituximab which is not necessarily the case with the treatment of B-cell malignancies...
2022: Frontiers in Medicine
https://read.qxmd.com/read/34788412/disparity-in-peripheral-and-renal-b-cell-depletion-with-rituximab-in-systemic-lupus-erythematosus-an-opportunity-for-obinutuzumab
#8
JOURNAL ARTICLE
Venkat R Reddy, Ruth J Pepper, Kavina Shah, Geraldine Cambridge, Scott R Henderson, Christian Klein, Loren Kell, Samuel J Taylor, David A Isenberg, Mark S Cragg, Maria J Leandro
OBJECTIVES: To investigate key factors that may contribute to the variability of rituximab-mediated peripheral and renal B cell depletion (BCD) in SLE. METHODS: We analysed: (i) CD19+ B cell counts in patients with SLE before and 1, 2, 3 and 6 months after treatment with rituximab, comparing them with RA patients; (ii) the presence of B cells in renal biopsies after rituximab therapy; (iii) whether the duration of BCD correlated with patient demographics and B cell expression of CD20 and FcγRIIb; and (iv) the effect of B cell activation factor (BAFF) on the efficiency of rituximab and obinutuzumab at inducing BCD in whole blood assays, in vitro...
July 6, 2022: Rheumatology
https://read.qxmd.com/read/34698499/effectiveness-of-belimumab-after-rituximab-in-systemic-lupus-erythematosus-a-randomized-controlled-trial
#9
RANDOMIZED CONTROLLED TRIAL
Muhammad Shipa, Andrew Embleton-Thirsk, Mariea Parvaz, Liliana Ribeiro Santos, Patrick Muller, Kashfia Chowdhury, David A Isenberg, Caroline J Doré, Caroline Gordon, Michael R Ehrenstein
BACKGROUND: B-cell depletion with rituximab is commonly used for patients with systemic lupus erythematosus (SLE) that is refractory to conventional therapy, but it yields variable responses. We hypothesized that high B-cell activating factor (BAFF) levels after rituximab can cause disease flares, thereby limiting its effectiveness. OBJECTIVE: To obtain preliminary evidence for efficacy of the anti-BAFF therapeutic belimumab after rituximab in SLE. DESIGN: Phase 2, randomized, double-blind (patients, assessors, researchers, care providers), placebo-controlled, parallel-group, superiority trial...
December 2021: Annals of Internal Medicine
https://read.qxmd.com/read/34240116/can-we-predict-if-patients-with-sle-will-require-more-than-one-cycle-of-rituximab
#10
JOURNAL ARTICLE
Raquel Fernández González, Rym Abida, Eugeniu Gisca, Leila Duarte, David A Isenberg
OBJECTIVE: To identify clinical and serological features that distinguish patients with SLE who require single as opposed to repeated rituximab (RTX) cycles. METHODS: All 175 SLE patients followed up at University College Hospital from 2000 onwards were retrospectively reviewed. They were divided into a one-RTX-cycle group and a multiple-cycle group (2 or more cycles). Patients included had a follow-up of at least 3 years after their first RTX cycle, unless they needed a second infusion sooner...
May 5, 2022: Rheumatology
https://read.qxmd.com/read/33629101/psychosis-in-systemic-lupus-erythematosus-sle-40-year-experience-of-a-specialist-centre
#11
JOURNAL ARTICLE
Esha Abrol, Ester Coutinho, Michael Chou, Melanie Hart, Angela Vincent, Robert Howard, Michael S Zandi, David Isenberg
OBJECTIVES: The long-term outcome of psychosis in association with Systemic Lupus Erythematosus (SLE) has been insufficiently characterised. We used a specialist centre cohort of patients with SLE and psychosis to investigate their clinical outcome and phenotypic and laboratory characteristics. METHODS: Retrospective cohort study of 709 SLE patients seen at a specialist centre between January 1978 and November 2018. Clinical, biochemical and immunological characteristics (Bonferroni corrected), and serum neuronal surface antibody profile using novel cell-based assays, were compared between patients with and without psychosis...
February 25, 2021: Rheumatology
https://read.qxmd.com/read/33521659/b-cell-depletion-with-rituximab-in-the-covid-19-pandemic-where-do-we-stand
#12
JOURNAL ARTICLE
Puja Mehta, Joanna C Porter, Rachel C Chambers, David A Isenberg, Venkat Reddy
No abstract text is available yet for this article.
October 2020: Lancet Rheumatology
https://read.qxmd.com/read/33472522/analysis-of-trends-and-causes-of-death-in-sle-patients-over-a-40-years-period-in-a-cohort-of-patients-in-the-united-kingdom
#13
JOURNAL ARTICLE
Ana Lorenzo-Vizcaya, David Isenberg
BACKGROUND: Systemic Lupus Erythematosus (SLE) an autoimmune rheumatic disease with a complex pathogenesis, remains potentially life-threatening. SLE patients have increased morbidity and premature mortality compared to non-SLE patients. The five-year survival rate has improved from <50% in the 1950s to >90% in the 1980s. Lupus patients still have a mortality risk three times that of the general population. OBJECTIVES: To provide a detailed analysis of the causes of death, main characteristics and trends in the management of the deceased SLE patients from the lupus clinic at the University College London Hospital (UCLH); during the past four decades...
April 2021: Lupus
https://read.qxmd.com/read/33459161/rituximab-the-first-twenty-years
#14
REVIEW
Maria Leandro, David A Isenberg
It is now two decades since Rituximab was first used in the treatment of patients with systemic lupus erythematosus. There have been many challenges but in spite of failing to meet its primary endpoints in two clinical trials it is widely used for many aspects of lupus, its side-effects and the possibility that combining it with Benlysta may be of value. We also consider the proposal that it may provide a useful initial therapy. In this review, we consider the place of Rituximab in the treatment of lupus and anticipate how developments in fully-humanized anti-CD20 monoclonals may well extend the "therapeutic life" of B-cell depletion as a viable treatment option...
March 2021: Lupus
https://read.qxmd.com/read/33100166/16th-international-congress-on-antiphospholipid-antibodies-task-force-report-on-antiphospholipid-syndrome-treatment-trends
#15
REVIEW
Hannah Cohen, Maria J Cuadrado, Doruk Erkan, Ali Duarte-Garcia, David A Isenberg, Jason S Knight, Thomas L Ortel, Anisur Rahman, Jane E Salmon, Maria G Tektonidou, David J Williams, Rohan Willis, Scott C Woller, Danieli Andrade
Antiphospholipid syndrome (APS), an acquired autoimmune thrombophilia, is characterised by thrombosis and/or pregnancy morbidity in association with persistent antiphospholipid antibodies. The 16th International Congress on Antiphospholipid Antibodies Task Force on APS Treatment Trends reviewed the current status with regard to existing and novel treatment trends for APS, which is the focus of this Task Force report. The report addresses current treatments and developments since the last report, on the use of direct oral anticoagulants in patients with APS, antiplatelet agents, adjunctive therapies (hydroxychloroquine, statins and vitamin D), targeted treatment including rituximab, belimumab, and anti-TNF agents, complement inhibition and drugs based on peptides of beta-2-glycoprotein I...
October 2020: Lupus
https://read.qxmd.com/read/32890026/biologic-therapies-for-systemic-lupus-erythematosus-where-are-we-now
#16
REVIEW
Grainne Murphy, David A Isenberg
PURPOSE OF REVIEW: Conventional approaches using hydroxychloroquine, corticosteroids and immunosuppressives have improved the prognosis for systemic lupus erythematosus (SLE) patients. Unfortunately, they have reached the limits of what they can achieve and patients still die prematurely and/or find their quality of life greatly impaired. Here, we discuss the problems of assessing activity in SLE, optimizing clinical trial design and more recent biologic approaches. RECENT FINDINGS: The success of B-cell depletion using Rituximab in open clinical studies, the approval of Belimumab (blocks the B-cell activating factor BAFF) and improvements in clinical trial design, gives cause for hope...
November 2020: Current Opinion in Rheumatology
https://read.qxmd.com/read/31951278/a-reverse-translational-study-on-the-effect-of-rituximab-rituximab-plus-belimumab-or-bortezomib-on-the-humoral-autoimmune-response-in-sle
#17
JOURNAL ARTICLE
Laura S van Dam, Zgjim Osmani, Sylvia W A Kamerling, Tineke Kraaij, Jaap A Bakker, Hans U Scherer, Ton J Rabelink, Reinhard E Voll, Tobias Alexander, David A Isenberg, Cees van Kooten, Y K Onno Teng
OBJECTIVES: SLE is a severe autoimmune disease characterized by autoreactive B cells and IC formation, which causes systemic inflammation. B cell-targeted therapy could be a promising treatment strategy in SLE patients; nevertheless, randomized clinical trials have not always been successful. However, some groups have demonstrated beneficial effects in severe SLE patients with off-label rituximab (RTX) with belimumab (BLM), or bortezomib (BTZ), which targeted different B cells subsets...
October 1, 2020: Rheumatology
https://read.qxmd.com/read/31848169/belimumab-after-b-cell-depletion-therapy-in-patients-with-systemic-lupus-erythematosus-beat-lupus-protocol-a-prospective-multicentre-double-blind-randomised-placebo-controlled-52-week-phase-ii-clinical-trial
#18
RANDOMIZED CONTROLLED TRIAL
Alexis Jones, Patrick Muller, Caroline J Dore, Felicia Ikeji, Emilia Caverly, Kashfia Chowdhury, David A Isenberg, Caroline Gordon, Michael R Ehrenstein
INTRODUCTION: Few treatment options exist for patients with systemic lupus erythematosus (SLE) who fail conventional therapy. Although widely used to treat lupus, the efficacy of B cell depletion therapy using rituximab has not been demonstrated in randomised clinical trials. Following rituximab, elevated levels of serum B cell activating factor (BAFF) have been associated with failure to remit or subsequent lupus relapse. The administration of belimumab, a monoclonal antibody specific for BAFF and approved for lupus therapy, could potentiate the efficacy of rituximab and enable longer periods of disease remission...
December 16, 2019: BMJ Open
https://read.qxmd.com/read/31485560/adverse-infusion-reactions-to-rituximab-in-systemic-lupus-erythematosus-a-retrospective-analysis
#19
JOURNAL ARTICLE
Ashleigh Hennessey, Joanna Lukawska, Geraldine Cambridge, David Isenberg, Maria Leandro
Background: To undertake a retrospective review of patients with SLE who had received Rituximab in order to determine the rates and associated patient characteristics of clinically significant adverse infusion reactions. Methods: A descriptive analysis was undertaken of each infusion reaction, which was then assessed using the clinical information available to hypothesise on the possible underlying mechanism(s). Results: Records of 136 SLE patients previously treated with 481 individual infusions of Rituximab were reviewed...
2019: BMC rheumatology
https://read.qxmd.com/read/31287404/why-do-some-patients-with-systemic-lupus-erythematosus-fail-to-respond-to-b-cell-depletion-using-rituximab
#20
JOURNAL ARTICLE
Sara Freitas, Marta Mozo Ruiz, Antonio Costa Carneiro, David A Isenberg
OBJECTIVES: The Centre for Rheumatology has treated 165 lupus patients with rituximab (RTX) since 2000. Our aim was to identify patients who failed to respond, identify any obvious distinguishing features, and to optimise individual patient treatment. METHODS: We reviewed all 165 lupus patients treated with RTX and reviewed the data up to 6 months after treatment. We excluded those who developed allergic reactions, had discoid lupus only or were lost to follow-up...
March 2020: Clinical and Experimental Rheumatology
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