NDT Advance Access originally published online on April 19, 2005
Nephrology Dialysis Transplantation 2005 20(6):1274; doi:10.1093/ndt/gfh852
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Rituximab is an alternative in a case of contra-indication of cyclophosphamide in Wegener's granulomatosis
Sir,We read with interest the report by Ferraro et al. [1] on the effectiveness of rituximab in refractory Wegener's granulomatosis (WG). We report a case of relapsing WG with remission under rituximab, whereas cyclophosphomide was contra-indicated.
WG was diagnosed in February 2002 in a 57-year-old hypertensive patient with fatigue, renal failure (creatinine 334 µmol/l), haematuria and serum PR3-ANCA at a titre of 1090 U/ml (positive >20). Renal biopsy disclosed nephroangiosclerosis and necrotizing glomerulonephritis. High dose corticosteroids and 12 cyclophosphamide pulses resulted in remission, but renal insufficiency led to dialysis. Maintenance therapy with azathioprine was given from August 2002 to July 2003. In February 2004, relapse occurred with fatigue and haemoptysia related to alveolar haemorrhage, with positive PR3-ANCA at a titre of 200 U/ml. Corticosteroids and a first cyclophosphamide pulse were administered but stopped because platelet count fell at 74 000/mm3. The alkaline phosphatase level was 334 UI/l (normal <100). Portal hypertension was demonstrated with grade II oesophageal varices due to veno-occlusive disease associated with nodular regenerative hyperplasia of the liver, probably induced by azathioprine. The patient received four weekly administrations of 375 mg/m2 of rituximab, inducing complete remission. Mycophenolate mofetil (1.0 g/d) was subsequently administered as maintenance therapy. No relapse has occurred to date.
This case highlights the interest of rituximab in WG, in the case of contra-indication of cyclophosphamide. A few case reports show that rituximab is effective in WG [1–3], but prospective studies are necessary in order to evaluate its indications, since rituximab seems favourable as compared to other drugs.
Conflict of interest statement. None declared.
1 Service de Médecine Interne CHU Tenon Paris France2 Unité d'Hépatogastroentérologie3 Service de Néphrologie Hôpital Laennec Creil France Email: claude.bachmeyer{at}tnn.ap-hp-paris.fr
References
- Ferraro AJ, Day CJ, Drayson MT, Savage CO. Effective therapeutic use of rituximab in refractory Wegener's granulomatosis. Nephrol Dial Transplant 2005; 20: 622–625
[Free Full Text] - Specks U, Fervenza FC, McDonald TJ, Hogan MC. Response of Wegener's granulomatosis to anti-CD20 chimeric monoclonal antibody therapy. Arthritis Rheum 2001; 44: 2836–2840[CrossRef][Web of Science][Medline]
- Kallenbach M, Duan H, Ring T. Rituximab induced remission in a patient with Wegener's granulomatosis. Nephron Clin Pract 2005; 99: c92–c96[CrossRef][Web of Science][Medline]
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  D E Furst, F C Breedveld, J R Kalden, J S Smolen, G R Burmester, J Sieper, P Emery, E C Keystone, M H Schiff, P Mease, et al. Updated consensus statement on biological agents for the treatment of rheumatic diseases, 2007 Ann Rheum Dis, November 1, 2007; 66(suppl_3): iii2 - iii22. [Full Text] [PDF]
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 K. A. Keogh, S. R. Ytterberg, F. C. Fervenza, K. A. Carlson, D. R. Schroeder, and U. Specks Rituximab for Refractory Wegener's Granulomatosis: Report of a Prospective, Open-Label Pilot Trial Am. J. Respir. Crit. Care Med., January 15, 2006; 173(2): 180 - 187. [Abstract] [Full Text] [PDF]
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