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

Abstract

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.

• Authors: Z Chocova, Z Hruskova, H Mareckova, B Svobodova, D Duskova, V Bednarova, E Jancova, R Rysava, V Tesar
• Journal: Clinical rheumatology (Clin Rheumatol) Vol. 34 Issue 1 Pg. 107-15 (Jan 2015) ISSN: 1434-9949 [Electronic] Germany
• PMID: 25388644 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal, Murine-Derived
• Immunoglobulin G
• Immunologic Factors
• Rituximab

Topics

• Adolescent
• Adult
• Aged
• Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis (drug therapy, immunology)
• Antibodies, Monoclonal, Murine-Derived (pharmacology, therapeutic use)
• Female
• Humans
• Immunity, Cellular (drug effects)
• Immunity, Humoral (drug effects)
• Immunoglobulin G (blood)
• Immunologic Factors (pharmacology, therapeutic use)
• Male
• Middle Aged
• Rituximab
• Treatment Outcome
• Young Adult