Rheumatology, Institute of Clinical Medicine, University of Tromsø, Rheumatology, University Hospital of North Norway, Tromsø, Norway and Division of Medicine, Royal Darwin Hospital, Department of Health, Darwin, Northern Territory, Australia.
Rituximab (RTX) is an anti-CD20 antibody used successfully in granulomatosis with polyangiitis (GPA) for induction and maintenance of remission. Our study aims to evaluate the long-term efficacy and safety of chronic pre-emptive RTX therapy in GPA.
Retrospective study of 35 GPA patients treated with RTX between April 2004 and September 2011 for active disease and maintenance. RTX was initiated as two 1 g infusions 2 weeks apart and thereafter 2 g of RTX was readministered annually. Patients were followed for 47 (2-88) months. They received a median RTX dose of 8 g (2-13) over 5 (1-10) rounds.
All patients had a clinical response, but nine relapses were recorded (flare rate of 6.6/100 patient-years). At last visit, 13 patients (37%) had discontinued RTX mainly due to hypogammaglobulinaemia (57%). Nine patients (26%) had severe infections (infection rate of 6.6/100 patient-years) and 10 patients (29%) had chronic infections. Risks factors for severe infections are a high cumulative dose of CYC, low CD4 cell count and a significant drop in total immunoglobulins after the first RTX round. Risks factors for chronic infections are low IgG level during RTX maintenance and possibly the cumulative RTX dose.
Long-term pre-emptive RTX maintenance was efficacious in reducing the risk for relapse but was discontinued in one-third of the patients. The patients' net state of immunodeficiency under RTX changes over time as low immunoglobulin serum levels increased the risk for infections.
"Retrospective data supports the use of repeated dosing with rituximab every 6 months for 2 years to maintain remission, with relapse rates of only 12 % during 24 months of treatment . There is, however, a risk of hypogammaglobulinaemia associated with long term treatment with rituximab . Randomised studies of rituximab versus azathioprine as maintenance therapy are ongoing. "
[Show abstract][Hide abstract] ABSTRACT: The small-vessel vasculitides are a group of disorders characterised by variable patterns of small blood vessel inflammation producing a markedly heterogeneous clinical phenotype. While any vessel in any organ may be involved, distinct but often overlapping sets of clinical features have allowed the description of three subtypes associated with the presence of circulating anti-neutrophil cytoplasmic antibodies (ANCA), namely granulomatosis with polyangiitis (GPA, formerly known as Wegener's Granulomatosis), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (eGPA, formerly known as Churg-Strauss syndrome). Together, these conditions are called the ANCA-associated vasculitidies (AAV). Both formal nomenclature and classification criteria for the syndromes have changed repeatedly since their description over 100 years ago and may conceivably do so again following recent reports showing distinct genetic associations of patients with detectable ANCA of distinct specificities. ANCA are not only useful in classifying the syndromes but substantial evidence implicates them in driving disease pathogenesis although the mechanism by which they develop and tolerance is broken remains controversial. Advances in our understanding of the pathogenesis of the syndromes have been accompanied by some progress in treatment, although much remains to be done to improve the chronic morbidity associated with the immunosuppression required for disease control.
Seminars in Immunopathology 07/2014; 36(4). DOI:10.1007/s00281-014-0436-6 · 7.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Introduction:
There are many mechanisms through which B lymphocytes have been implicated in the pathogenesis of glomerulonephritis. There are a number of trials and clinical studies in glomerulonephritis involving depletion of CD20(+) B lymphocytes using rituximab. Newer anti-CD20 agents are currently under evaluation, as are drugs targeting alternative B-cell targets such as B lymphocyte stimulator. Such selective, targeted B-cell therapies, if shown to be effective, may be of value in minimising toxicity from more conventional agents.
This article reviews the role of B cells as a target for therapy in adult renal disease resulting from primary glomerulonephritis and that occurring secondary to systemic disease. It will not address intracellular signalling or co-stimulatory pathways as therapeutic targets.
There are indications for B-cell targeted therapies in a number of adult glomerulonephritides, with varying degrees of evidence. Further understanding of the mechanisms of B-cell depletion and repletion, and interplay with B-cell survival factors, is necessary in order to identify patients who will respond favourably.
[Show abstract][Hide abstract] ABSTRACT: Rituximab is recognized as a useful drug for the treatment of B-cell non-Hodgkin's lymphoma and its use has been extended to such diseases as idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic purpura, chronic rheumatoid arthritis and ANCA-associated vasculitides. One serious complication associated with its use is the reactivation of hepatitis B virus and the search for methods to prevent this occurrence has resulted in the rapid accumulation of knowledge. In this review, we discuss case analyses from our department and other groups and outline the current knowledge on the topic and the remaining issues.
World Journal of Hepatology 11/2013; 5(11):612-620. DOI:10.4254/wjh.v5.i11.612
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