Rituximab use in patients with ANCA-associated vasculitis: clinical efficacy and impact on immunological parameters.
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; 15× PR3-ANCA, 3× MPO-ANCA; 16× relapsing/refractory, 2× 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 ≥6 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 (8× pre-emptive, 1× 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-γ 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.
Department of Nephrology, General University Hospital and First Faculty of Medicine, Charles University, U nemocnice 2, 128 08, Prague, Czech Republic, zdenka.chocova@vfn.cz.
Z
Z
Chocova
Z
Z
Hruskova
H
H
Mareckova
B
B
Svobodova
D
D
Duskova
V
V
Bednarova
E
E
Jancova
R
R
Rysava
V
V
Tesar
D000293:Adolescent; D000328:Adult; D000368:Aged; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000188:drug therapy* / Q000276:immunology; D058846:Antibodies, Monoclonal, Murine-Derived / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects*; D056724:Immunity, Humoral / Q000187:drug effects*; D007074:Immunoglobulin G / Q000097:blood; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D000069283:Rituximab; D016896:Treatment Outcome; D055815:Young Adult
D058846:Antibodies, Monoclonal, Murine-Derived; D007074:Immunoglobulin G; D007155:Immunologic Factors; D000069283:Rituximab