Rituximab-associated hypogammaglobulinaemia in ANCA-associated vasculitis and connective tissue diseases: a longitudinal observational study

被引:0
作者
Padoan, R. [1 ]
Felicetti, M. [1 ]
Gatto, M. [1 ]
Polito, P. [1 ]
Doria, A. [1 ]
Schiavon, F. [1 ]
机构
[1] Univ Padua, Dept Med DIMED, Rheumatol Unit, Padua, Italy
关键词
ANCA-associated vasculitis; connective tissue diseases; rituximab; hypogammaglobulinaemia; infections; B-CELL-DEPLETION; SERUM IMMUNOGLOBULIN LEVELS; RHEUMATOID-ARTHRITIS; PROFOUND HYPOGAMMAGLOBULINEMIA; MAINTENANCE THERAPY; RISK; CLASSIFICATION; SAFETY; CYCLOPHOSPHAMIDE; RECOMMENDATIONS;
D O I
暂无
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective. The burden of hypogammaglobulinaemia following rituximab (RTX) treatment in rheumatic diseases has not been fully elucidated yet. Our aim was to evaluate the frequency anti predictors of hypogammaglobulinaemia in patients affected by ANCA-associated vasculitis (AAV) and connective tissue diseases (CTD). Methods. We retrospectively reviewed prospectively collected data of patients receiving RTX. Imnunoglobulins (Ig) levels and lymphocyte subsets were recorded at RTX administration and 3-6 months later. We assessed frequency of hypogammaglobulinaemia (serum IgG<6 g/L) and its related events. Univariate and multi variable analysis were performed using SPSS 20.0 package. Results. Sixty-eight patients (30 AAV 25 systemic lupus erythematosus, 9 systemic sclerosis and 4 idiopathic inflammatory myopathies) were treated with RTX (95 infusions, median 2[2-6]). Following RTX, IgG<6 g/L were observed in 15/68 patients (15.8%), IgM<0.4 g/L in 28/68 (41%) and IgA<0.7 g/L in 7/68 (10.2%). Hypogammaglobulinaemia was more common in patients with AAV (p=0.008), short disease duration (p=0.001), low IgG levels at baseline (p=0.008), high cyclophosphamide exposure (p=0.018), high daily and cumulative prednisone dosage (p=0.001 and p=0.006). At multivariate analysis, cumulative cyclophosphamide dosage (OR 1.1 [1.0-1.3] p=0.045), daily prednisone intake >15mg (OR 9.5 [2.2-41.7] p=0.03) and IgG levels before RTX (OR 0.74 [0.59-0.931 p=0.009) were independent predictors of hypogammaglobulinaemia. Five patients experienced severe infections within 12 months, more frequently in those with IgG<6 g/L (26.7% vs 1.9%, p=0.007). Conclusion. Hypogammaglobulinae-Mia following RTX is uncommon in AAV and CTD and is more likely in patients with high glucocorticoids and cyclophosphamide exposure and low IgG levels at baseline.
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页码:S188 / S194
页数:7
相关论文
共 51 条
[1]   Use of Rituximab in Systemic Lupus Erythematosus: A Single Center Experience Over 14 Years [J].
Aguiar, R. ;
Araujo, C. ;
Martins-Coelho, G. ;
Isenberg, D. .
ARTHRITIS CARE & RESEARCH, 2017, 69 (02) :257-262
[2]   Long-term follow-up of patients who received repeat-dose rituximab as maintenance therapy for ANCA-associated vasculitis [J].
Alberici, Federico ;
Smith, Rona M. ;
Jones, Rachel B. ;
Roberts, Darren M. ;
Willcocks, Lisa C. ;
Chaudhry, Afzal ;
Smith, Kenneth G. C. ;
Jayne, David R. W. .
RHEUMATOLOGY, 2015, 54 (07) :1153-1160
[3]   PRELIMINARY CRITERIA FOR THE CLASSIFICATION OF SYSTEMIC-SCLEROSIS (SCLERODERMA) [J].
不详 .
ARTHRITIS AND RHEUMATISM, 1980, 23 (05) :581-590
[4]   Low immunoglobulin levels increase the risk of severe hypogammaglobulinemia in granulomatosis with polyangiitis patients receiving rituximab [J].
Besada, Emilio .
BMC MUSCULOSKELETAL DISORDERS, 2016, 17
[5]   Serum immunoglobulin levels and risk factors for hypogammaglobulinaemia during long-term maintenance therapy with rituximab in patients with granulomatosis with polyangiitis [J].
Besada, Emilio ;
Koldingsnes, Wenche ;
Nossent, Johannes C. .
RHEUMATOLOGY, 2014, 53 (10) :1818-1824
[6]   POLYMYOSITIS AND DERMATOMYOSITIS .2. [J].
BOHAN, A ;
PETER, JB .
NEW ENGLAND JOURNAL OF MEDICINE, 1975, 292 (08) :403-407
[7]   High incidence of non-neutropenic infections induced by rituximab plus fludarabine and associated with hypogammaglobulinemia: a frequently unrecognized and easily treatable complication [J].
Cabanillas, F. ;
Liboy, I. ;
Pavia, O. ;
Rivera, E. .
ANNALS OF ONCOLOGY, 2006, 17 (09) :1424-1427
[8]   Incidence of Hypogammaglobulinemia in Patients Receiving Rituximab and the Use of Intravenous Immunoglobulin for Recurrent Infections [J].
Casulo, Carla ;
Maragulia, Jocelyn ;
Zelenetz, Andrew D. .
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA, 2013, 13 (02) :106-111
[9]   Delayed-onset peripheral blood cytopenia after rituximab: Frequency and risk factor assessment in a consecutive series of 77 treatments [J].
Cattaneo, Chiara ;
Spedini, Pierangelo ;
Casari, Salvatore ;
Re, Alessandro ;
Tucci, Alessandra ;
Borlenghi, Erika ;
Ungari, Marco ;
Ruggeri, Giulia ;
Rossi, Giuseppe .
LEUKEMIA & LYMPHOMA, 2006, 47 (06) :1013-1017
[10]   Comparison of individually tailored versus fixed-schedule rituximab regimen to maintain ANCA-associated vasculitis remission: results of a multicentre, randomised controlled, phase III trial (MAINRITSAN2) [J].
Charles, Pierre ;
Terrier, Benjamin ;
Perrodeau, Elodie ;
Cohen, Pascal ;
Faguer, Stanislas ;
Huart, Antoine ;
Hamidou, Mohamed ;
Agard, Christian ;
Bonnotte, Bernard ;
Samson, Maxime ;
Karras, Alexandre ;
Jourde-Chiche, Noemie ;
Lifermann, Francois ;
Gobert, Pierre ;
Hanrotel-Saliou, Catherine ;
Godmer, Pascal ;
Martin-Silva, Nicolas ;
Pugnet, Gregory ;
Matignon, Marie ;
Aumaitre, Olivier ;
Viallard, Jean-Francois ;
Maurier, Francois ;
Meaux-Ruault, Nadine ;
Riviere, Sophie ;
Sibilia, Jean ;
Puechal, Xavier ;
Ravaud, Philippe ;
Mouthon, Luc ;
Guillevin, Loic .
ANNALS OF THE RHEUMATIC DISEASES, 2018, 77 (08) :1144-1150