Repeated decrease of CD4+ T-cell counts in patients with rheumatoid arthritis over multiple cycles of rituximab treatment

Matthieu Lavielle, Denis Mulleman, Philippe Goupille, Clément Bahuaud, Hsueh Cheng Sung, Hervé Watier, Gilles Thibault

Significant peripheral blood CD4+ T-cell depletion has been observed after a first cycle of rituximab, a monoclonal antibody directed against the CD20 antigen, which is currently used in rheumatoid arthritis. Of note, an absence of CD4+ T-cell decrease has been observed in non-responders. Herein, we describe CD4+ T-cell changes over repeated cycles of rituximab and their relationship with clinical outcomes. Patients with rheumatoid arthritis who started rituximab between July 2007 and July 2013 were analyzed up to November 2014. Lymphocyte phenotyping and clinical assessments were performed before, and 3 and 6 months after each cycle. Lymphocytes counts and disease activity were compared at each time point, using nonparametric tests. Patients received up to seven cycles of treatment during the study period. Mean CD4+ T-cell counts were above the upper limit of the reference range before each rituximab infusion and repeatedly reached the reference range at 6 months (and/or 3 months) post infusion. CD4+ T cells decreased concurrently with disease activity score. CD4+ T-cell counts could be a relevant biomarker of response to rituximab in rheumatoid arthritis and could be considered in making decisions about the timing of retreatment.