Rituximab use in patients with ANCA-associated vasculitis: clinical efficacy and impact on immunological parameters

被引:16
作者
Chocova, Z. [1 ,2 ]
Hruskova, Z. [1 ,2 ,3 ]
Mareckova, H. [2 ,3 ]
Svobodova, B. [1 ,2 ]
Duskova, D. [2 ,4 ]
Bednarova, V. [1 ,2 ]
Jancova, E. [1 ,2 ]
Rysava, R. [1 ,2 ]
Tesar, V. [1 ,2 ]
机构
[1] Charles Univ Prague, Dept Nephrol, Gen Univ Hosp, Prague 12808, Czech Republic
[2] Charles Univ Prague, Fac Med 1, Prague 12808, Czech Republic
[3] Charles Univ Prague, Inst Microbiol & Immunol, Gen Univ Hosp, Prague 12808, Czech Republic
[4] Charles Univ Prague, Dept Med 1, Gen Univ Hosp, Dept Clin Haematol, Prague 12808, Czech Republic
关键词
ANCA; B cell depletion; Cellular immunity; Outcome; Rituximab; T cells; Vasculitis; B-CELL DEPLETION; REMISSION; CYCLOPHOSPHAMIDE; GRANULOMATOSIS; MAINTENANCE; THERAPY;
D O I
10.1007/s10067-014-2816-7
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Rituximab (RTX) was reported effective in ANCA-associated vasculitis (AAV). We aimed to evaluate clinical efficacy of RTX in AAV along with its impact on immunological parameters. Eighteen RTX-treated AAV patients (M/F 11/7; median age 37.5; 15x PR3-ANCA, 3x MPO-ANCA; 16x relapsing/refractory, 2x first-line therapy) were enrolled. Clinical response, ANCA, total serum IgG levels and cellular immunity parameters were examined. The patients were followed up (FU) for a median of 26 months (range 3-82, 15 for a parts per thousand yen6 months). All patients achieved B cell depletion (lasting 3-24 months). No significant increase was noted in T cell or NK cell subpopulations. At 6 months, partial remission was achieved in 5/15 patients (33 %) and complete in 8 (53 %). The median prednisone dose (30..10 mg/d) and ANCA levels (17.2..2.7 IU/mL) decreased (p < 0.01). RTX retreatment was used in nine (8x pre-emptive, 1x relapse). Six patients relapsed (none of the pre-emptively treated). Three patients died of infection. IgG levels at 3 months decreased compared to baseline (9.0 vs 5.7 g/L, p < 0.01). Higher percentage of HLA-DR+CD3+ cells and lower percentage of CD4+CD45RA+ naive T cells persisted during FU. IFN-gamma production increased at 6 months compared to baseline (27.3 vs 41.5 %). No significant change was noted in the intracellular IL-10 and IL-12 production. RTX helped to lower the glucocorticosteroids dose and withdraw cytotoxic drugs in most AAV patients. Hypogammaglobulinaemia was common but well tolerated. Peripheral circulating T cells remained activated despite B cell depletion.
引用
收藏
页码:107 / 115
页数:9
相关论文
共 19 条
[1]   Impact of rituximab trials on the treatment of ANCA-associated vasculitis [J].
Alberici, Federico ;
Jayne, David R. W. .
NEPHROLOGY DIALYSIS TRANSPLANTATION, 2014, 29 (06) :1151-1159
[2]   Rituximab for remission induction and maintenance in refractory granulomatosis with polyangiitis (Wegener's) Ten-year experience at a single center [J].
Cartin-Ceba, Rodrigo ;
Golbin, Jason M. ;
Keogh, Karina A. ;
Peikert, Tobias ;
Sanchez-Menendez, Marta ;
Ytterberg, Steven R. ;
Fervenza, Fernando C. ;
Specks, Ulrich .
ARTHRITIS AND RHEUMATISM, 2012, 64 (11) :3770-3778
[3]  
Flossmann O, 2007, ANN RHEUM DIS, V66, P283, DOI 10.1136/ard.2005.051078
[4]   Intracellular Cytokine Production in ANCA-associated Vasculitis: Low Levels of Interleukin-10 in Remission Are Associated with a Higher Relapse Rate in the Long-term Follow-up [J].
Hruskova, Zdenka ;
Rihova, Zuzana ;
Mareckova, Helena ;
Jancova, Eva ;
Rysava, Romana ;
Zavada, Jakub ;
Merta, Miroslav ;
Loester, Tomas ;
Tesar, Vladimir .
ARCHIVES OF MEDICAL RESEARCH, 2009, 40 (04) :276-284
[5]   2012 Revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides [J].
Jennette, J. C. ;
Falk, R. J. ;
Bacon, P. A. ;
Basu, N. ;
Cid, M. C. ;
Ferrario, F. ;
Flores-Suarez, L. F. ;
Gross, W. L. ;
Guillevin, L. ;
Hagen, E. C. ;
Hoffman, G. S. ;
Jayne, D. R. ;
Kallenberg, C. G. M. ;
Lamprecht, P. ;
Langford, C. A. ;
Luqmani, R. A. ;
Mahr, A. D. ;
Matteson, E. L. ;
Merkel, P. A. ;
Ozen, S. ;
Pusey, C. D. ;
Rasmussen, N. ;
Rees, A. J. ;
Scott, D. G. I. ;
Specks, U. ;
Stone, J. H. ;
Takahashi, K. ;
Watts, R. A. .
ARTHRITIS AND RHEUMATISM, 2013, 65 (01) :1-11
[6]   Rituximab versus Cyclophosphamide in ANCA-Associated Renal Vasculitis. [J].
Jones, Rachel B. ;
Tervaert, Jan Willem Cohen ;
Hauser, Thomas ;
Luqmani, Raashid ;
Morgan, Matthew D. ;
Peh, Chen Au ;
Savage, Caroline O. ;
Segelmark, Marten ;
Tesar, Vladimir ;
van Paassen, Pieter ;
Walsh, Dorothy ;
Walsh, Michael ;
Westman, Kerstin ;
Jayne, David R. W. .
NEW ENGLAND JOURNAL OF MEDICINE, 2010, 363 (03) :211-220
[7]   A Multicenter Survey of Rituximab Therapy for Refractory Antineutrophil Cytoplasmic Antibody-Associated Vasculitis [J].
Jones, Rachel B. ;
Ferraro, Alastair J. ;
Chaudhry, Afzal N. ;
Brogan, Paul ;
Salama, Alan D. ;
Smith, Kenneth G. C. ;
Savage, Caroline O. S. ;
Jayne, David R. W. .
ARTHRITIS AND RHEUMATISM, 2009, 60 (07) :2156-2168
[8]   Rituximab for refractory Wegener's granulomatosis - Report of a prospective, open-label pilot trial [J].
Keogh, KA ;
Ytterberg, SR ;
Fervenza, FC ;
Carlson, KA ;
Schroeder, DR ;
Specks, U .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2006, 173 (02) :180-187
[9]   Rituximab-induced B cell depletion in autoimmune diseases: Potential effects on T cells [J].
Liossis, Stamatis-Nick C. ;
Sfikakis, Petros P. .
CLINICAL IMMUNOLOGY, 2008, 127 (03) :280-285
[10]   Persistent T-cell activation and clinical correlations in patients with ANCA-associated systemic vasculitis [J].
Marinaki, Smaragdi ;
Kaelsch, Anna-Isabelle ;
Grimminger, Peter ;
Breedijk, Annette ;
Birck, Rainer ;
Schmitt, Wilhelm H. ;
Weiss, Christel ;
Woude, Fokko J. van der ;
Yard, Benito A. .
NEPHROLOGY DIALYSIS TRANSPLANTATION, 2006, 21 (07) :1825-1832