Tocilizumab in the treatment of arthritis: response to therapy and evaluation of B cells subsets after 4 months treatment

Background: IL-6 has pleiotropics effects on immune system cells; in rheumatoid arthritis, it is responsible for ESR and CRP elevation, articular damage and clinical activity. Blocking IL-6 receptor with Tocilizumab leads to clinical improvement of arthritis and seems to reduce peripheral pre- and post-switch memory B cells in rheumatoid arthritis. To evaluate B cells subsets distribution and their relation to clinical improvement after Tocilizumab therapy. Methods: 5 patients (3 rheumatoid arthritis, 1 juvenile rheumatoid arthritis and 1 adult onset Still disease) were treated with monthly 8 mg/kg intravenous tocilizumab. Peripheral B subset distribution was evaluated with flow-cytometry (IgD-CD27) at baseline and after 4 months of treatment. Clinical data was collected and disease activity was assessed using DAS over time. Results: A significant reduction of ESR and CRP was observed after 4 months therapy (ESR: 41.0±27.9 vs 8.4±7.9mm/1st hr, p=0.01; CRP:51.3±86.6 vs 1.7±1.7 mg/l, p=0.01) even if DAS reduction didn’t reach statistical significance (3.5±0.4 vs 2.1±1.6, p=0.09) due to a limited reduction of swollen and tender joints count (SJC:5.8±5.0 vs 2.6±3.6, p=0.31; TJC:10.0±10.8 vs 8.0±6.4, p=0.84). Considering B cells subsets, we observed a tendon to a decrease of percentage of pre-switch memory B cells (IgD+CD27+: 26.9±22.9% at baseline vs 14.2±15.3% at 4th month FU, p=0.22) and an increase of frequency of naïve B-cells (IgD+CD27-: 36.6±21.2% vs 57.7±14.9%, p=0.15) after treatment. A parallel decreased of CD19+/ZAP70+ during FU was observed (8.9±5.5% vs 2.7±2.0%, p=0.19). Memory B cells (CD27+IgD-) weren’t modified by treatment. Conclusions: Tocilizumab rapidly reduce inflammation and even in a short term follow-up seems to alter the peripheral B cells phenotype.