NK cell count as predictor of clinical response in patients with rheumatoid arthritis treated with rituximab.

Purpose: The relationship between antiCD20 therapy with rituximab and the lymphocytes phenotype in patients with rheumatoid arthritis was investigated, with an attempt to establish a relationship between commonly used clinical activity indices and variations in leukocyte count, in particular natural killer (NK) lymphocytes.

Methods: Patients with seropositive (cyclic citrullinated peptides and rheumatoid factor positive) rheumatoid arthritis (according to the American College of Rheumatology 1987 criteria) refractory to conventional and antitumor necrosis factor-alpha agents who were subsequently treated with rituximab, a chimeric monoclonal antibody directed against CD20, were enrolled between January 2009 and September 2009. All subjects were treated with rituximab standard rheumatologic dose of 1.0 g on days 1 and 15 every 6 months for at least 2 years. A clinical evaluation was performed at baseline and subsequently every 3 months thereafter. At each assessment activated NK (CD56+/CD16+/CD54bright) cell count was collected and disease activity was assessed using Disease Activity Score in 28 Joints and the Simplified Disease Activity Index (SDAI).

Results: Thirty-four patients were enrolled (mean age ± standard deviation: 54.8 ± 12.8 years). Basal SDAI was 21.75 ± 5.4 and NK cell count mean value was 157.6 ± 90. After 24 months, SDAI was 14 ± 1.2 and NK cell count mean value was 301.7 ± 21 (P < 0.05). An inverted correlation between SDAI and NK count was observed at 3 months (r = -0.36, P < 0.05), 6 months (r = -0.48, P < 0.45), 9 months (r = -0.47, P < 0.05), 12 months (r = -0.41, P < 0.01), 15 months (r = -0.58, P < 0.05), 18 months (r = -0.53, P < 0.05), 21 months (r = -0.68, P < 0.05), and 24 months (r = -0.61, P < 0.05). A linear regression model between all variables collected and SDAI/Disease Activity Score in 28 Joints at 6 months and 12 months confirmed a significant relationship between SDAI/Disease Activity Score in 28 Joints and NK cell count.

Conclusion: The data confirm the clinical efficacy of rituximab and suggests the use of NK cells as a predictor of clinical response in patients with rheumatoid arthritis.