A novel glucocorticoid-free maintenance regimen for anti-neutrophil cytoplasm antibody–associated vasculitis

Pepper, Ruth J.; McAdoo, Stephen P.; Moran, Sarah; Kelly, Dearbhla M.; Scott, Jennifer; Hamour, Sally; Burns, Áine; Griffith, Megan; Galliford, Jack; Levy, Jeremy; Cairns, Thomas; Gopaluni, Seerapani; Jones, Rachel; Jayne, David; Little, Mark A.; Pusey, Charles D.; Salama, Alan D.

doi:10.1093/rheumatology/key288

Cited by 49 publications

(49 citation statements)

References 34 publications

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“…A recent study reported outcomes in 49 patients treated with a glucocorticoid-sparing regime. Here, the investigators used a cumulative dose of <0.7 g within the first three months [ 28 ]. However, and in contrast to our cohort, patients in this study and in PEXIVAS were routinely treated with intravenous methylprednisolone (up to 3 g) at disease presentation.…”

Section: Discussionmentioning

confidence: 99%

Long-term outcomes in elderly patients with ANCA-associated vasculitis

et al. 2019

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Objective ANCA-associated vasculitis (AAV) is a small vessel vasculitis that commonly presents in the elderly. However, there are few long-term outcome data for these patients. Here, we assessed long-term outcomes in a single-centre cohort of elderly patients with AAV. Additionally, we tested whether a pre-morbid frailty score could aid prognosis. Methods Using a prospectively-compiled dataset, we investigated patients over the age of 65 who presented with AAV between 2005 and 2017 to a regional vasculitis centre. We used a Cox model to determine the factors associated with mortality. We also compared outcomes in pre-specified subgroups stratified by baseline frailty score, ANCA serotype and induction immunosuppression (with cyclophosphamide, rituximab or mycophenolate mofetil used as the main glucocorticoid-sparing agent). Results 83 patients were included in the study and were followed for a median of 1203 days. Median age was 74 years (range 65–92). Two- and five-year survival in the overall cohort were 83% (95% CI 75, 92%) and 75% (95% CI 65, 86%), respectively. The median cumulative dose of oral prednisolone was 2030 mg during the first three months. Only one patient received intravenous glucocorticoids. Age, frailty score and CRP at presentation were independently associated with mortality; all deaths occurred in patients aged over 75 at presentation. Patients treated with a cyclophosphamide-based induction regimen tended to be younger than those treated with rituximab or mycophenolate mofetil. Survival was better in the cyclophosphamide-treated group. Conclusion In the contemporary era, the overall prognosis of AAV in elderly patients is good. Baseline frailty associates with disease outcomes including mortality. A low-dose glucocorticoid regimen (avoiding intravenous methylprednisolone) can be used to treat AAV effectively in elderly patients.

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Section: Discussionmentioning

confidence: 99%

Long-term outcomes in elderly patients with ANCA-associated vasculitis

et al. 2019

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“…Today, high dose glucocorticoids plus either rituximab or cyclophosphamide are used more often. Case series using combination rituximab and cyclophosphamide to spare glucocorticoid exposure have been published, but the evidence base supporting this practice remains weak 9697. The main limitation to use of rituximab is its cost,98 although biosimilar rituximab may cost less 99.…”

Section: Induction Of Remissionmentioning

confidence: 99%

“…The optimal dose and duration of glucocorticoid treatment remains an area of active investigation in both induction and maintenance of remission 125167168169170. For example, a single center study of 49 patients found that the combination of rituximab and cyclophosphamide with two weeks or less of glucocorticoids led to 96% of patients achieving remission at six months 125…”

Section: Emerging Treatmentsmentioning

confidence: 99%

Management of ANCA associated vasculitis

Wallace

Miloslavsky

2020

BMJ

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Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) is a small to medium vessel vasculitis associated with excess morbidity and mortality. This review explores how management of AAV has evolved over the past two decades with pivotal randomized controlled trials shaping the management of induction and maintenance of remission. Contemporary AAV care is characterized by approaches that minimize the cumulative exposure to cyclophosphamide and glucocorticoids, increasingly use rituximab for remission induction and maintenance, and consider therapies with less toxicity (for example, methotrexate, mycophenolate mofetil) for manifestations of AAV that do not threaten organ function or survival. Simultaneously, improvements in outcomes, such as renal and overall survival, have been observed. Additional trials and observational studies evaluating the comparative effectiveness of agents for AAV in various patient subgroups are needed. Prospective studies are necessary to assess the effect of psychosocial interventions on patient reported outcomes in AAV. Despite the expanding array of treatments for AAV, little guidance on how to personalize AAV care is available to physicians.

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“…One such combination approach using low-dose intravenous cyclophosphamide and rituximab, along with a rapid oral glucocorticoid taper, has been described in an open-label cohort study. Rates of remission at 6 months, mortality, long-term relapse rates, and renal outcomes were favorable when compared to those in matched historical controls from European Vasculitis Study Group studies (74,75). A similar approach, using a short course of oral cyclophosphamide and rituximab, has been reported in a single-center, retrospective case series of 129 patients, again showing favorable rates of remission induction and relapse (76).…”

Section: Combination Drug Therapymentioning

confidence: 56%

New Therapeutic Targets in Antineutrophil Cytoplasm Antibody–Associated Vasculitis

Prendecki

McAdoo

2021

Arthritis & Rheumatology

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Antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) is a rare systemic autoimmune disease that is characterized by necrotizing inflammation of predominantly the small blood vessels and the presence of circulating ANCAs directed against myeloperoxidase or proteinase 3. Current treatment strategies for severe disease, supported by the findings of several well-coordinated randomized controlled trials, aim to induce remission with high-dose glucocorticoids and either rituximab or cyclophosphamide, followed by relapse prevention with a period of sustained low-dose treatment. This approach has dramatically improved outcomes in AAV; however, a significant proportion of patients develop serious treatment-related side effects or experience relapse. Recent advances in our understanding of the pathogenesis of AAV have led to the identification of novel therapeutic targets that may address these problems, including strategies directed at the aberrant adaptive autoimmune response (B and T cell-directed treatments) and those targeting innate immune elements (complement, monocytes, and neutrophils). It is anticipated that these novel treatments, used alone or in combination, will lead to more effective and less toxic treatment regimens for patients with AAV.

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A novel glucocorticoid-free maintenance regimen for anti-neutrophil cytoplasm antibody–associated vasculitis

Abstract: Early GC withdrawal in severe AAV is as effective for remission induction as the standard of care and is associated with reduced GC-related adverse events.

Cited by 49 publications

References 34 publications

Long-term outcomes in elderly patients with ANCA-associated vasculitis

Long-term outcomes in elderly patients with ANCA-associated vasculitis

Management of ANCA associated vasculitis

New Therapeutic Targets in Antineutrophil Cytoplasm Antibody–Associated Vasculitis

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