Rituximab versus Cyclophosphamide in ANCA-Associated Renal Vasculitis

Jones, Rachel; Tervaert, Jan Willem Cohen; Hauser, Thomas; Luqmani, Raashid; Morgan, Matthew D.; Peh, Chen Au; Savage, Caroline O.S.; Segelmark, Mårten; Tesař, Vladimı́r; Paassen, Pieter van; Walsh, Dorothy; Walsh, Michael; Westman, Kerstin; Jayne, David

doi:10.1056/nejmoa0909169

Cited by 1,511 publications

(1,079 citation statements)

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“…The serious adverse effects of continuous oral cyclophosphamide have been greatly reduced by a pulse regime or by substituting less-toxic immunosuppressive agents for induction and/or maintenance treatment, albeit at the expense of a higher relapse rate. Since publication of the 2010 Peripheral Nerve Society guideline 4 , evidence has shown that rituximab is at least as efficacious as cyclophosphamide for induction of remission and more efficacious than azathioprine in the maintenance of remission in the ANCA-associated vasculitides [142][143][144] . The most up-to-date guidelines on the treatment of the ANCA-associated vasculitides were published by the British Society for Rheumatology in 2014 (REF.…”

Section: Evidence From Systemic Vasculitismentioning

confidence: 99%

The nonsystemic vasculitic neuropathies

2017

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The vasculitides are a clinically diverse group of diseases with the histopathological signature of blood vessel-centred inflammation that results in vascular damage and ischaemic injury to the affected tissues 1 . Vasculitis can be caused by drugs, infections and cancers, but diagnostic workup reveals no trigger in most patients. Autoimmune mechanisms are active in all vasculitides, except those caused by direct infection of vessel walls. Most vasculitides are systemic and involve multiple organs and tissues. Those affecting small-to medium-sized vessels often manifest with a vasculitic neuropathy. For example, neuropathies occur in 60-70% of patients with polyarteritis nodosa, eosinophilic granulomatosis with polyangiitis and cryoglobulinaemic vasculitis, and 40-50% of those with microscopic polyangiitis and rheumatoid vasculitis 2 .Vasculitic neuropathy can also occur without systemic vasculitis. This single-organ vasculitis of the PNS has commonly been referred to as nonsystemic vasculitic neuropathy (NSVN), but other forms of clinically isolated PNS vasculitis are now recognized and can be considered variants of NSVN 3 . Although NSVN is classically an acute, relapsing, multifocal neuropathy, it can present as a slowly progressive neuropathy without distinct asymmetries. As such, it should be considered as a possible cause of any progressive axonal neur opathy. NSVN can be diagnosed only with a nerve biopsy, with or without a concomitant muscle or skin biopsy; as nerve biopsies are seldom performed, the condition is under-recognized. The disorder must be distinguished from many other causes of multifocal neuropathy, the definition of which is itself not standardized and requires clarification.A Peripheral Nerve Society guideline group reviewed the literature on vasculitic neuropathy and published consensus recommendations on the classification, diagnosis and immunosuppressive treatment of NSVN in 2010 (REF. 4) Abstract | Nonsystemic vasculitic neuropathy (NSVN) is an under-recognized single-organ vasculitis of peripheral nerves that can only be diagnosed with a nerve biopsy. A Peripheral Nerve Society guideline group published consensus recommendations on the classification, diagnosis and treatment of NSVN in 2010, and new diagnostic criteria for vasculitic neuropathy were developed by the Brighton Collaboration in 2015. In this Review, we provide an update on the classification, diagnosis and treatment of NSVN. NSVN subtypes include Wartenberg migratory sensory neuropathy and postsurgical inflammatory neuropathy. Variants include diabetic radiculoplexus neuropathy and -arguably -neuralgic amyotrophy. NSVN with proximal involvement is sometimes termed nondiabetic lumbosacral radiculoplexus neuropathy. Cutaneous polyarteritis nodosa and other skin-nerve vasculitides overlap with NSVN clinically. Three patterns of involvement in NSVN have been identified: multifocal neuropathy, distal symmetric polyneuropathy, and overlapping multifocal neuropathy (asymmetric polyneuropathy). These patterns lack standard defi...

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Section: Evidence From Systemic Vasculitismentioning

confidence: 99%

The nonsystemic vasculitic neuropathies

2017

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“…Based on the results of open-label studies, two randomized studies were designed to test the efficacy of RTX as induction therapy compared to standard treatment with cyclophosphamide [21] and [22]. The RITUXVAS (RTX versus Cyclophosphamide in ANCA-Associated Renal Vasculitis) study [21] randomized 44 patients with AAV and renal involvement to either receive RTX 375 mg/m2 weekly for 4 doses in addition to steroids and 2 doses of intravenous cyclophosphamide or to conventional therapy, including steroids, cyclophosphamide for 3-6 months, and azathioprine maintenance.…”

Section: Anti-neutrophil Cytoplasmic Antibody (Anca)-associated Smallmentioning

confidence: 99%

“…The RITUXVAS (RTX versus Cyclophosphamide in ANCA-Associated Renal Vasculitis) study [21] randomized 44 patients with AAV and renal involvement to either receive RTX 375 mg/m2 weekly for 4 doses in addition to steroids and 2 doses of intravenous cyclophosphamide or to conventional therapy, including steroids, cyclophosphamide for 3-6 months, and azathioprine maintenance. Remission rates (76% in RTX vs. 82% in conventional therapy) and adverse events (42% in RTX vs. 36% in conventional therapy) were similar in both groups.…”

Section: Anti-neutrophil Cytoplasmic Antibody (Anca)-associated Smallmentioning

confidence: 99%

Rituximab-based novel strategies for the treatment of immune-mediated glomerular diseases

Kattah¹,

Fervenza²,

Roccatello³

2013

Autoimmunity Reviews

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Rituximab is a monoclonal antibody to the CD20 antigen on B-cells that was initially designed and approved for the treatment of non-Hodgkin's B-cell lymphoma in 1997.In the last 15 years, it has emerged as a potent immunosuppressant for many immune-mediated diseases, beginning initially with rheumatoid arthritis, and now extending into several other fields, including clinical nephrology. Based on recent large clinical trials, it is FDA-approved for the treatment of ANCA-associated vasculitis and continues to be studied in off-label usage for many glomerular diseases, including membranous nephropathy, lupus nephritis, and mixed cryoglobulinemia. It has been used as a treatment in nephrotic syndrome in children and adults, including both minimal change disease and focal segmental glomerulosclerosis. Given its efficacy, tolerability and safety profile in comparison to more conventional treatment regimens, RTX is rapidly emerging as a critical treatment modality in glomerular disease.

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“…Furthermore, it may be considered particularly in relapsing patients (38,42,43). In a subgroup analysis, RTX at 6 months was found to be superior to CYC in inducing remission in those who relapsed than CYC in patients enrolled in the Rituximab in ANCA-Associated Vasculitis (RAVE) trial (39). Evaluation over a longer period of time of patients in the RAVE trial with severe AAV found that a single course of RTX was as effective as continuous conventional immunosuppressive therapy for induction and maintenance of remission over an 18-month period (44).…”

Section: Discussionmentioning

confidence: 99%