NDT Advance Access originally published online on November 9, 2006
Nephrology Dialysis Transplantation 2007 22(1):291-293; doi:10.1093/ndt/gfl501
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Anti-CD20 antibody treatment in refractory Class IV lupus nephritis
Email: doctorrobertcarroll{at}yahoo.comSir,
Selected cases of class IV lupus nephritis patients have been treated with rituximab monotherapy [1,2] and in combination with cyclophosphamide [3]. Data on refractory patients who have failed multiple therapies are limited [4]. We have successfully treated four patients with rituximab, who have failed multiple conventional immunosuppressive regimens, including cyclophosphamide, azathioprine, mycophenolate and ciclosporin. Patient characteristics and response to rituximab are summarized in Tables 1 and 2, respectively.
|
|
Patient 1
A third episode of class IV nephritis failed to respond to four cycles of cyclophosphamide and rendered her neutropenic. Concurrently, she had evidence of cerebral and cutaneous lupus. She was treated with methylprednisolone and ciclosporin but her renal and cerebral disease failed to respond, and she received a single infusion of 500 mg rituximab. All clinical features began to improve within 10 days. Clinical relapse at 9 months was retreated with two weekly infusions of 500 mg rituximab. At 26 months, her B cell count rose from 20 to 200 cells/µl and there was evidence of renal and immunological relapse and she was retreated with four infusions of rituximab. The B cell count fell and she clinically improved. She remains stable at 36 months and is maintained on 10 mg prednisolone.
Patient 2
A fifth episode of class IV nephritis failed to respond to three cycles of cyclophosphamide. Due to bone marrow suppression, cyclophosphamide could not be continued. She received three 700 mg infusions of rituximab, and the parameters improved. At 19 months post initial infusion, she was retreated due to reappearance of active urinary sediment and a doubling of her proteinuria. At 3 months post second infusion, she has demonstrated serological and clinical improvement. Her current drug regimen is azathioprine 25 mg and prednisolone 10 mg.
Patient 3
A fourth episode of class IV lupus could not be treated with cyclophosphamide as he was suffering borderline neutropenia from maintenance therapy with azathioprine. The patient had also been treated with ciclosporin in the past and there was evidence of ciclosporin toxicity on biopsy. He received two weekly 600 mg infusions of rituximab. He is stable at 26 months and still has B cell depletion (24 cells/µl). His current drug regimen is 10 mg prednisolone and the ciclosporin dose was halved to 50 mg bd.
Patient 4
He presented with symptoms of nephrotic syndrome but was also anaemic and thrombocytopenic. Biopsy showed class IV/V lupus nephritis. He had received multiple courses of cyclophosphamide and because of concerns regarding bone marrow suppression, he was treated with three 500 mg infusions of rituximab. Due to a past history of TB and splenectomy, he has been maintained on prophylactic penicillin and isoniazid. At 16 months, he has stable parameters and is maintained on low-dose azathioprine and prednisolone.
All patients had pre-existing B cell lymphopenia prior to Rituximab 22 ± 18 cell/µl (mean ± SD). This possibly relates to high dose steroids, previous cyclophosphamide and disease activity. Improvement occurred in the context of pre-existing B cell lymphopenia and this has been reported by Weide et al. [2]. In spite of B cell lymphopenia, none of the patients suffered severe infection.
In summary, rituximab monotherapy can induce long-term remission in patients with Class IV SLE nephritis, including those previously treated with cyclophosphamide and with severe or relapsing disease. Also, this clinical improvement can still take place in the context of pre-existing B cell lymphopenia.
Conflict of interest statement. None declared.
Monash Medical Centre
Nephrology
Melbourne
Victoria
Australia
References
- Sfiakis P, Boletis J, Vigklis V, Fragiadaki K, Moutsopoulos H. (2005) Remission of proliferative lupus nephritis following B cell depletion therapy is preceded by downregulation of T cell costimulation molecule CD40 ligand: an open label study. Arthritis Rheum 52:371–377.[CrossRef][Web of Science][Medline]
- Weide R, Heymanns J, Pandorf A, Koppler H. (2003) Successful long-term treatment of systemic lupus erythematosus with rituximab maintenance therapy. Lupus 12:779–782.
[Abstract/Free Full Text] - Leandro MJ, Cambridge G, Edwards JC, Ehrenstein MR, Isenberg DA. (2005) B-cell depletion in the treatment of patients with systemic lupus erythematosus: a longitudinal analysis of 24 patients. Rheumatology 44:1542–1545.
[Abstract/Free Full Text] - Van den Bergh B, Selleslag D, Boelaert JR, et al. (2005) Management of therapy-resistant systemic lupus erythematosus with rituximab: report of a case and review of the literature. Acta Clin Belg 60:102–105.[Web of Science][Medline]
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  C. Melander, M. Sallee, P. Trolliet, S. Candon, X. Belenfant, E. Daugas, P. Remy, V. Zarrouk, E. Pillebout, C. Jacquot, et al. Rituximab in Severe Lupus Nephritis: Early B-Cell Depletion Affects Long-Term Renal Outcome Clin. J. Am. Soc. Nephrol., March 1, 2009; 4(3): 579 - 587. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 B. Ranchin and S. Fargue Review: New treatment strategies for proliferative lupus nephritis: keep children in mind! Lupus, August 1, 2007; 16(8): 684 - 691. [Abstract] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||