Extended versus standard azathioprine maintenance therapy in newly diagnosed proteinase-3 anti-neutrophil cytoplasmic antibody-associated vasculitis patients who remain cytoplasmic anti-neutrophil cytoplasmic antibody-positive after induction of remission: a randomized clinical trial

Sanders, Jan-Stephan; Joode, Anoek A. E. de; DeSevaux, Ruud G.; Broekroelofs, J.; Voskuyl, Alexandre E.; Paassen, Pieter van; Kallenberg, Cees G. M.; Tervaert, Jan Willem Cohen; Stegeman, Coen A.

doi:10.1093/ndt/gfw211

Cited by 58 publications

(43 citation statements)

References 19 publications

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“…In this study, patients who were C-ANCA positive at the time of switch had a significantly higher chance for a relapse compared to patients who were ANCA negative (relative risk 2.6 [95% CI 1.1-8.0]) [34]. Recently, however, these results could not be reproduced in a prospective study [72].…”

Section: Persistence Of Anca Positivitymentioning

confidence: 57%

“…Few studies have investigated the therapeutic potential to guide therapy based on serial ANCA measurements [61,72,74,75]. In the initial study performed in the 1980s, 57 patients were followed and ANCA was monthly measured [61].…”

Section: Therapy Based On Anca Levelsmentioning

confidence: 99%

“…up to 24 months after diagnosis) period of azathioprine maintenance therapy in order to prevent relapses. It was concluded that extended azathioprine maintenance therapy does not result in a longer period of sustained remission [72].…”

Section: Therapy Based On Anca Levelsmentioning

confidence: 99%

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Maintaining remission in patients with granulomatosis with polyangiitis or microscopic polyangiitis: the role of ANCA

Kemna¹,

Paassen²,

Damoiseaux³

et al. 2017

Expert Opinion on Orphan Drugs

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Introduction: Granulomatosis with Polyangiitis (GPA; formerly Wegener's) and Microscopic Polyangiitis (MPA) are inflammatory disease entities affecting small to medium vessels. They are characterized by the presence of anti-neutrophil cytoplasmic antibodies (ANCA) and are frequently grouped together with Eosinophilic Granulomatosis with Polyangiitis (EGPA; formerly Churg Strauss Syndrome) under the term ANCA-associated Vasculitis (AAV). Due to effective immunosuppressive therapy that was introduced more than 45 years ago, AAV has become a chronic disease in which relapses occur frequently during maintenance treatment or later on after all immunosuppressive therapy is stopped. Since relapses are associated with morbidity and mortality, early detection and prevention of relapses is of great importance. Areas covered: This review focuses on the potential strategies to guide maintenance therapy in patients with GPA or MPA, with an emphasis on patient classifications and the role of serial ANCA measurements. Expert opinion: Risk factors for relapses, e.g., genetic background of the patient, have been studied during the last three decades. Only few of these risk factors directly influence the management of patients. One potentially important factor that may influence therapeutic decisions in AAV patients is serial measurement of ANCA. Recently, it became clear that serial ANCA measurement is an attractive approach in AAV patients with (a history of) capillaritis, e.g., renal involvement or alveolar haemorrhage, but not in patients with more limited disease. Whether ANCA rises can be used to guide therapy andhence-to prevent relapses has been a great debate during the last three decades. At present, we conclude that small studies do support such an approach but that these findings require further validation in larger randomized clinical trials. ARTICLE HISTORY

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Section: Persistence Of Anca Positivitymentioning

confidence: 57%

Section: Therapy Based On Anca Levelsmentioning

confidence: 99%

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Maintaining remission in patients with granulomatosis with polyangiitis or microscopic polyangiitis: the role of ANCA

Kemna¹,

Paassen²,

Damoiseaux³

et al. 2017

Expert Opinion on Orphan Drugs

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“…Only one previous study has compared different regimens, in patients with persistent anti-PR3-ANCA positivity at remission. Sanders et al 17 randomised 45 patients to receive either standard (1 year after diagnosis and subsequent tapering) or extended (4 years after diagnosis and tapered thereafter) azathioprine maintenance therapy. Although 46% of patients relapsed in the standard therapy group versus 24% in the extended therapy group, the difference was not statistically different.…”

Section: Discussionmentioning

confidence: 99%

Randomised controlled trial of prolonged treatment in the remission phase of ANCA-associated vasculitis

et al. 2017

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“…Patients with PR3-ANCA (versus MPO-ANCA), lung, or upper respiratory tract vasculitis have a higher risk for relapse that warrants longer maintenance therapy (52,53). However, in a randomized controlled trial of patients with PR3-ANCA disease who remained ANCA-positive at the time of stable remission, extending the duration of maintenance therapy with azathioprine from 1 year (followed by taper) to 4 years (followed by taper) was not associated with a significant difference in relapse-free survival at 4 years (54). The result of this study should not be extrapolated to other agents, and the optimal duration of maintenance therapy with rituximab has not been formally evaluated.…”

Section: Maintenance Of Remissionmentioning

confidence: 99%

ANCA Glomerulonephritis and Vasculitis

Jennette¹,

Nachman²

2017

CJASN

268

214

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ANCA vasculitis has an associated autoimmune response that produces ANCAs that induce distinct pathologic lesions. Pauci-immune necrotizing and crescentic GN is a frequent component of ANCA vasculitis. ANCA vasculitis is associated with ANCA specific for myeloperoxidase (MPO-ANCA) or proteinase 3 (PR3-ANCA). A diagnosis of ANCA vasculitis should always specify the serotype as MPO-ANCA positive, PR3-ANCA positive, or ANCAnegative. To fully characterize a patient, the serotype also should be accompanied by the clinicopathologic variant if this can be determined: microscopic polyangiitis, granulomatosis with polyangiitis (Wegener), eosinophilic granulomatosis with polyangiitis (Churg-Strauss), or renal-limited vasculitis. ANCA vasculitis is most prevalent in individuals >50 years old. There are racial/ethnic and geographic influences on the prevalence, serotype frequencies, and clinicopathologic phenotypes. There is clinical, in vitro, and animal model evidence that ANCAs cause disease by activating neutrophils to attack small vessels. Immunomodulatory and immunosuppressive therapies are used to induce remission, maintain remission, and treat relapses. Over recent years, there have been major advances in optimizing treatment by minimizing toxic therapy and utilizing more targeted therapy.

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Extended versus standard azathioprine maintenance therapy in newly diagnosed proteinase-3 anti-neutrophil cytoplasmic antibody-associated vasculitis patients who remain cytoplasmic anti-neutrophil cytoplasmic antibody-positive after induction of remission: a randomized clinical trial

Abstract: ClinicalTrials.gov NCT 00128895.

Cited by 58 publications

References 19 publications

Maintaining remission in patients with granulomatosis with polyangiitis or microscopic polyangiitis: the role of ANCA

Maintaining remission in patients with granulomatosis with polyangiitis or microscopic polyangiitis: the role of ANCA

Randomised controlled trial of prolonged treatment in the remission phase of ANCA-associated vasculitis

ANCA Glomerulonephritis and Vasculitis

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