Article Text

PDF
THU0213 Cyclophosphamide has no efficacy in japanese patients with renal vasculitis associated with anti-neutrophil cytoplasmic antibody-positive microscopic polyangiitis
  1. I. Nakaya1,
  2. M. Iwabuchi2,
  3. Y. Tsuchiya2,
  4. Y. Shibagaki3,
  5. T. Yamaguchi4,
  6. S. Fukuhara5,
  7. Y. Oe2,
  8. M. Yahata1,
  9. J. Soma1,
  10. T. Sato2,
  11. Y. Taguma2
  1. 1Department of Nephrology, Iwate Prefectural Central Hospital, Morioka
  2. 2Department of Nephrology, Sendai Shakai Hoken Hospital, Sendai
  3. 3Division of Nephrology and Hypertension, St. Marianna University School of Medical Hospital, Kawasaki
  4. 4Department of Biostatistics, Tohoku University School of Medicine, Sendai
  5. 5Department of Epidemiology and Healthcare Research, Graduate School of Medicine and Public Health, Kyoto University, Kyoto, Japan

Abstract

Background Cyclophosphamide (CY) has been recognized to improve the survival rate of patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in Europe. However, AAV background in Japan has been reported to be different from that in Europe. Myeloperoxidase (MPO)-ANCA-associated microscopic polyangiitis (MPA) constitutes a large part of AAV in Japan. Moreover, the effect of CY on the disease is controversial in Japan.

Objectives The aim of this study was to elucidate the effect of CY on ANCA-positive MPA with renal involvement in Japan.

Methods Eighty-two patients newly diagnosed with ANCA-positive MPA by renal biopsies in two general hospitals in Japan between 2000 and 2010 were enrolled in this retrospective study. The exclusion criteria were as follows: patients with coexistent cancer; serum creatinine greater than 5.0 mg/dL; and age younger than 20 years. Patients were divided into two groups based on whether they received combination therapy with a corticosteroid (CS) plus CY (CY-group), or CS alone or CS plus other therapies aside from CY (non-CY-group) for remission induction. The primary outcome was defined as the combination of death and end-stage renal disease (ESRD). We performed survival analysis using Kaplan-Meier method and Cox regression models.

Results The CY-group included 29 patients, 20 of whom were treated with oral CY and 9 with intravenous CY. The non-CY-group included 53 patients, 31 of whom were treated with CS alone, and 22 with a combination of CS and other therapeutics including intravenous immunoglobulin, mizoribine, and lymphocyte apheresis. The percentage of male, the mean Birmingham vasculitis activity scores (BVAS) were higher in the CY-group than in the non-CY-group (79% vs. 57% and 18.0±5.2 vs. 14.7±3.8, respectively).Only two patients were proteinase 3-ANCA positive in the CY-group and none in the non-CY-group.There were no differences in age, serum creatinine, serum albumin, C-reactive protein (CRP), pathological score, or initial dosage of prednisolone (PSL) between the two groups. Fourteen primary outcomes (8 deaths and 6 ESRDs) occurred in the CY-group and 14 (9 deaths and 5 ESRDs) in the non-CY-group. The 1- and 5-years survival rates were 0.89 and 0.47 in the CY-group, and 0.87 and 0.75 in the non-CY-group, respectively (p=0.065). Age and serum Alb were found to be related to the primary outcome by univariate analysis. However, serum creatinine, CRP, pathological score and initial dosage of PSL were not related to the same. Among patients receiving CY, the unadjusted hazard ratio forthe primary outcome was 2.028 and the hazard ratio adjusted for age and sex was 1.701. The hazard ratio adjusted for age, sex, BVAS and serum Alb was decreased to 1.519 (95% CI, 0.632-3.648; P=0.351).

Conclusions CY therapy caused an increase in the risk of death and ESRD by 52% compared with non-CY therapy among Japanese patients with renal vasculitis associated with ANCA-positive MPA, although the difference was not significant. Thus there is a highly possibility that CY should not be used for induction therapy among Japanese patientswith renal vasculitis associated with ANCA-positive MPA.

Disclosure of Interest None Declared

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.