Pulse versus daily oral cyclophosphamide for induction of remission in ANCA-associated vasculitis: long-term follow-up

Harper, Lorraine; Morgan, Matthew D.; Walsh, Michael; Höglund, Peter; Westman, Kerstin; Floßmann, Oliver; Tesař, Vladimı́r; Vanhille, P; Groot, Kirsten de; Luqmani, Raashid; Flores‐Suárez, Luis Felipe; Watts, Richard A.; Pusey, Charles D.; Bruchfeld, Annette; Rasmussen, Niels; Blockmans, Daniel Engelbert; Savage, Caroline O. S.; Jayne, David

doi:10.1136/annrheumdis-2011-200477

Cited by 360 publications

(209 citation statements)

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“…In those patients with AAV and active GN (creatinine ,5.7 mg/dl [500 mmol/L]), a pulsed regime induced remission as well as the daily oral regimen, with a decreased cumulative dose and fewer instances of leukopenia (9). Although long-term data demonstrated that the pulsed CYP regimen was associated with higher relapse rates, there was no difference in mortality or morbidity (10).…”

Section: Introductionmentioning

confidence: 80%

“…This study comprises too few patients to address this issue. Short-and long-term follow-up of patients from the CYCLOPS study (randomized trial of daily oral versus pulsed cyclophosphamide) reported more relapses in the pulsed CYP group (9) with no differences in renal relapses, and importantly no difference in long-term renal outcome or mortality (10).…”

Section: Discussionmentioning

confidence: 99%

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Intravenous Cyclophosphamide and Plasmapheresis in Dialysis-Dependent ANCA-Associated Vasculitis

Pepper

Chanouzas

Tarzi

et al. 2013

Clinical Journal of the American Society of Nephrology

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Study (EUVAS) investigators SummaryBackground and objectives Induction therapy with oral cyclophosphamide (CYP) has been a mainstay of treatment in patients with severe renal failure secondary to ANCA-associated vasculitis (AAV). Recent evidence proposes using pulsed intravenous CYP in less severe disease to minimize adverse events. It is unclear if this can be translated to those with dialysis-dependent renal insufficiency.Design, setting, participants, & methods All AAV patients presenting between 2005 and 2010 requiring dialysis at presentation were retrospectively analyzed. Patients were treated with plasma exchange, corticosteroids, and intravenous CYP. Rate of dialysis independence at 3 and 12 months and adverse effects were assessed and compared with the outcome of the plasmapheresis, prednisolone, and oral CYP arm of the randomized MEPEX (methylprednisolone versus plasma exchange) trial.Results Forty-one patients were included. At 3 months, 3 (7.3%) patients had died on dialysis, 12 (29.3%) remained dialysis dependent, and 26 (63.4%) were dialysis independent (creatinine, 2.5 mg/dl; GFR, 26 ml/min per 1.73 m 2 ). Four patients subsequently reached ESRD at a median time of 83 days. Thirty-seven (90%) patients reached 1 year follow-up, 13 (35%) remained dialysis dependent, and 24 (65%) had independent renal function. Eleven patients (27%) had episodes of leukopenia (white cell count ,4310 9 /L) during CYP therapy and 17 (41%) experienced infectious complications. This compares favorably with the dialysis-dependent cohort treated with plasmapheresis in the MEPEX study in which 51% were alive with independent renal function at 1 year.Conclusions Intravenous CYP used with corticosteroids and plasmapheresis may be an effective alternative to oral CYP in patients with dialysis-dependent AAV.

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Section: Introductionmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Intravenous Cyclophosphamide and Plasmapheresis in Dialysis-Dependent ANCA-Associated Vasculitis

Pepper

Chanouzas

Tarzi

et al. 2013

Clinical Journal of the American Society of Nephrology

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“…146 However, for polyangiitis with granulomatosis a randomized trial of daily oral dosing versus intravenous cyclophosphamide (the CYCLOPS trial) showed that oral dosing was more effective in the long term. 147 I have no experience of intravenous administration. 109 Tauber 1991: 105 patients.…”

Section: Use Of Systemic Immunomodulation To Control Immunemediated Imentioning

confidence: 99%

The 2016 Bowman Lecture Conjunctival curses: scarring conjunctivitis 30 years on

Dart

2017

Eye

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This review is in two sections. The first section summarises 35 conditions, both common and infrequent, causing cicatrising conjunctivitis. Guidelines for making a diagnosis are given together with the use of diagnostic tests, including direct and indirect immunofluorescence, and their interpretation. The second section evaluates our knowledge of ocular mucous membrane pemphigoid, which is the commonest cause of cicatrizing conjunctivitis in most developed countries. The clinical characteristics, demographics, and clinical signs of the disease are described. This is followed by a review and re-evaluation of the pathogenesis of conjunctival inflammation in mucous membrane pemphigoid (MMP), resulting in a revised hypothesis of the autoimmune mechanisms causing inflammation in ocular MMP. The relationship between inflammation and scarring in MMP conjunctiva is described. Recent research, describing the role of aldehyde dehydrogenase (ALDH) and retinoic acid (RA) in both the initiation and perpetuation of profibrotic activity in MMP conjunctival fibroblasts is summarised and the potential for antifibrotic therapy, using ALDH inhibition, is discussed. The importance of the management of the ocular surface in MMP is briefly summarised. This is followed with the rationale for the use of systemic immunomodulatory therapy, currently the standard of care for patients with active ocular MMP. The evidence for the use of these drugs is summarised and guidelines given for their use. Finally, the areas for research and innovation in the next decade are reviewed including the need for better diagnostics, markers of disease activity, and the potential for biological and topical therapies for both inflammation and scarring.

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“…Our patient was placed on daily oral CYC along with corticosteroids, since she had an increased risk of relapse due to her age and rapidly worsening kidney function, as well as the presence of the sclerosis pattern in the tissue specimen. Harper et al evaluated the long-term outcomes of the 148 patients previously enrolled in the CYCLOPS study (35). At a median duration of 4.3 years, patient survival was similar between the 2 treatment arms, despite an increased risk of relapse in patients treated with pulse CYC (35).…”

Section: Discussionmentioning

confidence: 99%

“…Harper et al evaluated the long-term outcomes of the 148 patients previously enrolled in the CYCLOPS study (35). At a median duration of 4.3 years, patient survival was similar between the 2 treatment arms, despite an increased risk of relapse in patients treated with pulse CYC (35). In addition, our patient's serum creatinine rapidly worsened during her hospitalization, with a serum creatinine level Ͻ500 moles/liter (5.7 mg/dl), suggestive of severe and rapidly progressive renal vasculitis, immediately life-threatening disease, and poor renal outcome at a 1-year interval (30); therefore, she was treated with a course of plasma exchange (7 sessions in 2 weeks) in conjunction with the prednisone and oral CYC.…”

Section: Discussionmentioning

confidence: 99%

An Unusual Case of Hematuria

Najem

Sfeir

Estrada

et al. 2014

Arthritis Care & Research

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Pulse versus daily oral cyclophosphamide for induction of remission in ANCA-associated vasculitis: long-term follow-up

Abstract: Pulse cyclophosphamide is associated with a higher relapse risk than DO cyclophosphamide. However, this is not associated with increased mortality or long-term morbidity. Although the study was retrospective, data was returned in 90% of patients from the original trial.

Cited by 360 publications

References 19 publications

Intravenous Cyclophosphamide and Plasmapheresis in Dialysis-Dependent ANCA-Associated Vasculitis

Intravenous Cyclophosphamide and Plasmapheresis in Dialysis-Dependent ANCA-Associated Vasculitis

The 2016 Bowman Lecture Conjunctival curses: scarring conjunctivitis 30 years on

An Unusual Case of Hematuria

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