B cell repopulation kinetics after rituximab treatment in ANCA-associated vasculitides compared to rheumatoid arthritis, and connective tissue diseases: a longitudinal observational study on 120 patients

• Published in: Arthritis research & therapy Vol. 19; no. 1; p. 101
• Main Authors: Thiel, Jens, Rizzi, Marta, Engesser, Marie, Dufner, Ann-Kathrin, Troilo, Arianna, Lorenzetti, Raquel, Voll, Reinhard E, Venhoff, Nils
• Format: Journal Article
• Language: English
• Published: England BioMed Central 18-05-2017; BMC
• Subjects: Adult; Aged; ANCA; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis - drug therapy; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis - immunology; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis - metabolism; Antirheumatic Agents - pharmacology; Antirheumatic Agents - therapeutic use; Arthritis; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - immunology; Arthritis, Rheumatoid - metabolism; Autoimmune diseases; B lymphocyte; B-Lymphocytes - drug effects; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; Colleges & universities; Connective Tissue Diseases - drug therapy; Connective Tissue Diseases - immunology; Connective Tissue Diseases - metabolism; Female; Follow-Up Studies; Humans; Hypogammaglobulinemia; Immunoglobulins; Immunotherapy; Inflammatory bowel disease; Longitudinal Studies; Lupus; Lymphocytes; Male; Middle Aged; Monoclonal antibodies; Observational studies; Patients; Repopulation; Retrospective Studies; Rheumatoid arthritis; Rheumatology; Rituximab; Rituximab - pharmacology; Rituximab - therapeutic use; Treatment Outcome; B lymphocyte; Rituximab; Hypogammaglobulinemia; Repopulation; ANCA
• ISSN: 1478-6362; 1478-6354; 1478-6362
• DOI: 10.1186/s13075-017-1306-0

B cell depletion with rituximab (RTX) is approved for treatment of rheumatoid arthritis (RA) and ANCA-associated vasculitides (AAV). Recently, RTX has been shown to be effective in AAV maintenance therapy, but an optimal RTX treatment schedule is unknown and the time to B cell repopulation after RTX has not been studied.
Retrospective single-center analysis of B cell repopulation in patients with AAV, RA or connective tissue disease (CTD) treated with RTX.
Beginning B cell repopulation within the first year after RTX treatment was observed in 93% of RA and 88% of CTD patients. Only 10% of patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) and no patient with eosinophilic granulomatosis with polyangiitis (EGPA) showed B cell repopulation within this time. Median time of B cell depletion was 26 months in GPA/MPA, and 21 months in EGPA compared to 9 months in RA, and 8 months in CTD (p < 0.0001). In 25 AAV-patients B cell depletion lasted for at least 44 months. There was a significant decline in serum immunoglobulin concentrations in GPA/MPA patients, but not in patients with RA or CTD. Significantly more GPA/MPA patients developed hygogammaglobulinemia (IgG <7 g/L) compared to patients with RA or CTD.
In contrast to RA and CTD, in AAV RTX induces long-lasting depletion of B cells that is associated with decreased antibody production. This observation points toward potential defects in the B cell compartment in AAV that are unmasked by immunosuppressive treatment and has important implications for the design of maintenance treatment schedules using RTX.