Rituximab Versus Cyclophosphamide for ANCA-Associated Vasculitis with Renal Involvement

Geetha, Duvuru; Specks, Ulrich; Stone, John H.; Merkel, Peter A.; Seo, Philip; Spiera, Robert; Langford, Carol A.; Hoffman, Gary S.; Kallenberg, Cees G. M.; Clair, E. William St.; Fessler, Barri J.; Ding, Linna; Tchao, Nadia K.; Iklé, David; Jepson, Brett; Brunetta, Paul; Fervenza, Fernando C.

doi:10.1681/asn.2014010046

Cited by 148 publications

(126 citation statements)

References 21 publications

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“…The RAVE trial demonstrated that 64% of patients treated with rituximab compared with 53% of those treated with cyclophosphamide achieved remission at 6 months, and patients responded similarly to either form of induction when they had renal involvement [3,8] . Although this trial excluded patients with serum creatinine >4 mg/ dl, 31% of patients had eGFR <30 ml/min/1.73 m 2 .…”

Section: Discussionmentioning

confidence: 99%

Treatment of Severe Renal Disease in ANCA Positive and Negative Small Vessel Vasculitis with Rituximab

et al. 2015

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Background/Aims: Rituximab and glucocorticoids are a non-inferior alternative to cyclophosphamide and glucocorticoid therapy for induction of remission in antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) patients with moderate renal disease. The efficacy and safety of this approach in patients with severe renal impairment are unknown. We report the outcomes and safety profile of rituximab and glucocorticoid therapy for induction of remission in patients with AAV and ANCA-negative vasculitis presenting with severe renal disease. Methods: A multicenter, retrospective, cohort study was conducted between 2005 and 2014. Patients with new or relapsing disease with an estimated glomerular filtration rate (eGFR) of ≤20 ml/min/1.73 m² treated with rituximab and glucocorticoid induction with or without plasmapheresis were included. Fourteen patients met the inclusion criteria. The primary outcomes were rate of remission and dialysis independence at 6 months. The secondary outcomes were eGFR at 6 months, end-stage renal disease (ESRD), survival rates and adverse events. Results: All patients were Caucasian, and 57% were male. The mean eGFR was 12 ml/min/1.73 m² at diagnosis. All patients achieved remission with a median time to remission of 55 days. Seven patients required dialysis at presentation of which 5 patients recovered renal function and discontinued dialysis by 6-month follow-up. The mean eGFR for the 11 patients without ESRD who completed 6-month follow-up was 33 ml/min/1.73 m². Four patients ultimately developed ESRD, and one died during the follow-up period. Conclusion: Patients with AAV and severe renal disease achieve high rates of remission and dialysis independence when treated with rituximab and glucocorticoids without cyclophosphamide.

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Section: Discussionmentioning

confidence: 99%

Treatment of Severe Renal Disease in ANCA Positive and Negative Small Vessel Vasculitis with Rituximab

et al. 2015

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“…Specks et al (2013) suggested that RTX therapy is inferior to CY therapy for refractory myeloperoxidase-ANCA. However, our data suggest that single dose RTX therapy is equivalent to a CY regimen for induction in patients newly diagnosed with AAV (Geetha et al 2015). In the present study, one patient, Patient 3, developed a serious infection, which is an important finding.…”

Section: Discussionmentioning

confidence: 49%

“…In the present study, one patient, Patient 3, developed a serious infection, which is an important finding. As mentioned above, a traditional RTX dose of 375 mg/m 2 for 4 consecutive weeks resulted in a total infection rate of 36-60% (Stone et al 2010;Geetha et al 2015), suggesting that single-dose RTX therapy may reduce complications from infections. Lowering the incidence of infectious complications is a key factor in controlling vasculitis.…”

Section: Discussionmentioning

confidence: 90%

“…Other advances in the development of AAV therapeutics have also improved prognosis (Koyama et al 2009). Recently, rituximab (RTX), a monoclonal antibody against CD20 (which is primarily found on the surface of B cells), has been used in the treatment of AAV (Greco et al 2015) and has been reported to be as effective as CY (Stone et al 2010;Geetha et al 2015). However, approximately 36-60% of patients receiving RTX treatment develop infections (Stone et al 2010;Geetha et al 2015).…”

Section: Introductionmentioning

confidence: 99%

“…Recently, rituximab (RTX), a monoclonal antibody against CD20 (which is primarily found on the surface of B cells), has been used in the treatment of AAV (Greco et al 2015) and has been reported to be as effective as CY (Stone et al 2010;Geetha et al 2015). However, approximately 36-60% of patients receiving RTX treatment develop infections (Stone et al 2010;Geetha et al 2015). Nagafuchi et al (2015) reported that Japanese patients receiving RTX for the treatment of refractory AAV showed beneficial outcomes; however, these patients also developed various infections.…”

Section: Introductionmentioning

confidence: 99%

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Remission Induction Therapy with Rituximab for Microscopic Polyangiitis: A Feasibility Study

Saito¹,

Takeuchi²,

Kagaya³

et al. 2017

Tohoku J. Exp. Med.

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Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is systemic vascular inflammation. Microscopic polyangiitis (MPA) is a major type of AAV in Japan. MPA often affects the kidneys and lungs, leading to death if untreated. Induction therapy (i.e., initial treatment) for MPA has not been optimized, although methylprednisolone and cyclophosphamide are commonly used. Recently, rituximab (RTX) (a monoclonal antibody against the protein CD20) has also been used to treat refractory AAV. RTX at 375 mg/m 2 /week for 4 weeks (i.e., the conventional lymphoma dosing schedule) is used, but the optimal dosing schedule is controversial. Indeed, a single-dose of RTX successfully controlled nephrotic syndrome. However, to date, the effectiveness of a single RTX dose in treating MPA has not been fully investigated in Japan. This was a retrospective observational study. Six newly diagnosed patients with MPA were initially treated with methylprednisolone and a single dose of RTX (375 mg/m 2 ). We investigated the patients' clinical features, as well as the efficacy and safety of RTX treatment. All patients attained remission on a tapered prednisolone dose of < 10 mg/day during the first 12 months. One patient relapsed after 12 months whereas another required hospitalization owing to infective spondyloarthritis. Adverse reactions to RTX infusion and late-onset neutropenia were not observed. Therefore, a single-dose treatment with RTX induced remission with few complications, and allowed tapering the prednisolone treatment. We conclude that a single dose of RTX is a promising induction therapy for MPA, reducing the cost associated with multiple doses.

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Interventions for renal vasculitis in adults

Walters¹,

Willis

Craig

2015

Cochrane Database of Systematic Reviews

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Rituximab Versus Cyclophosphamide for ANCA-Associated Vasculitis with Renal Involvement

Cited by 148 publications

References 21 publications

Treatment of Severe Renal Disease in ANCA Positive and Negative Small Vessel Vasculitis with Rituximab

Treatment of Severe Renal Disease in ANCA Positive and Negative Small Vessel Vasculitis with Rituximab

Remission Induction Therapy with Rituximab for Microscopic Polyangiitis: A Feasibility Study

Interventions for renal vasculitis in adults

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