Incidence of malignancy in patients treated for antineutrophil cytoplasm antibody-associated vasculitis: follow-up data from European Vasculitis Study Group clinical trials

Heijl, Caroline; Harper, Lorraine; Floßmann, Oliver; Stücker, Isabelle; Scott, Dgi; Watts, Richard A.; Höglund, Peter; Westman, Kerstin; Mahr, Alfred

doi:10.1136/ard.2010.145250

Cited by 133 publications

(105 citation statements)

References 30 publications

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“…The IR reported here was similar to the IRs in other patient populations (2)(3)(4)21). Surprisingly, malignancy risk was only 1.7 times higher in cyclophosphamide-treated patients compared with age-and sex-matched persons in the general population.…”

Section: Discussionsupporting

confidence: 67%

“…Current guidelines advise treatment with steroids and alkylating agents in patients who are at high risk for ESRD or have severe, persistent nephrosis (1). However, many physicians and patients are reluctant to use cyclophosphamide because of the increased risk of cancer after cyclophosphamide therapy in patients with granulomatosis with polyangiitis (formerly Wegener's granulomatosis), rheumatoid arthritis, and non-Hodgkin's lymphoma (2)(3)(4). Ascertaining the association between cyclophosphamide therapy and malignancy in iMN is challenging because of the concomitant immunosuppressive therapy, the relative rarity of malignancies, and the fact that membranous nephropathy may occur secondary to cancer (5,6).…”

Section: Introductionmentioning

confidence: 99%

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Cancer Risk after Cyclophosphamide Treatment in Idiopathic Membranous Nephropathy

Brand

Dijk

Hofstra

et al. 2014

Clinical Journal of the American Society of Nephrology

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Background and objectives Cyclophosphamide treatment improves renal survival in patients with idiopathic membranous nephropathy. However, use of cyclophosphamide is associated with cancer. The incidence of malignancies in patients with idiopathic membranous nephropathy was evaluated, and the cancer risk associated with cyclophosphamide use was estimated.Design, setting, participants, & measurements Patients who attended the clinic were included prospectively from 1995 on. A crude incidence ratio for the occurrence of malignancy was calculated. Incidence ratios were subsequently standardized to potential confounders. Latency between cyclophosphamide therapy and the occurrence of cancer was estimated by stratifying for time since the start of treatment. Finally, Poisson regression was used to obtain a multiple adjusted incidence ratio and investigate the dose-response relationship between cyclophosphamide and cancer.Results Data were available for 272 patients; the mean age was 51 years, and 70% of the patients were men. Median follow-up was 6.0 years (interquartile range=3.6-9.5), and 127 patients were treated with cyclophosphamide. Cancer incidence was 21.2 per 1000 person-years in treated patients compared with 4.6 per 1000 personyears in patients who did not receive cyclophosphamide, resulting in crude and adjusted incidence ratios of 4.6 (95% confidence interval, 1.5 to 18.8) and 3.2 (95% confidence interval, 1.0 to 9.5), respectively.Conclusion Cyclophosphamide therapy in idiopathic membranous nephropathy gives a threefold increase in cancer risk. For the average patient, this finding translates into an increase in annual risk from approximately 0.3% to 1.0%. The increased risk of malignancy must be balanced against the improved renal survival.

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Section: Discussionsupporting

confidence: 67%

Section: Introductionmentioning

confidence: 99%

Cancer Risk after Cyclophosphamide Treatment in Idiopathic Membranous Nephropathy

Brand

Dijk

Hofstra

et al. 2014

Clinical Journal of the American Society of Nephrology

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“…Immunosuppressive therapy for AAV also seems to have evidence for an association with increased risk [59], although the number of cancer cases is very small and thus there should be some reservation on the exact magnitude of the effect. The sporadic associations of medications with specific cancer types at one site should be seen with even greater caution.…”

Section: Discussionmentioning

confidence: 99%

Potential increased risk of cancer from commonly used medications: an umbrella review of meta-analyses

et al. 2014

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“…Moreover, there was an apparent increased rate of urotoxicity in patients receiving oral rather than intravenous CYP, even when correcting for cumulative dose (6). However, even with reduced duration of CYP exposure, a higher cancer rate than the general population has been found in AAV patients, suggesting that further improvements with regard to malignant risk are desirable (7).…”

Section: Introductionmentioning

confidence: 92%

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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Incidence of malignancy in patients treated for antineutrophil cytoplasm antibody-associated vasculitis: follow-up data from European Vasculitis Study Group clinical trials

Cited by 133 publications

References 30 publications

Cancer Risk after Cyclophosphamide Treatment in Idiopathic Membranous Nephropathy

Cancer Risk after Cyclophosphamide Treatment in Idiopathic Membranous Nephropathy

Potential increased risk of cancer from commonly used medications: an umbrella review of meta-analyses

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

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