Monitoring of Epstein-Barr virus (EBV)/cytomegalovirus (CMV)/varicella-zoster virus (VZV) load in patients receiving tocilizumab for rheumatoid arthritis

Abstract

Introduction: IL-6 is involved in viral immunosurveillance. We studied the effect of tocilizumab (TCZ) on the evolution in viral load (VL) for the Epstein-Barr virus (EBV), cytomegalovirus (CMV) and varicella-zoster virus (VZV) in patients with rheumatoid arthritis (RA).

Methods: EBV, CMV and VZV loads were prospectively determined in whole blood of 22 RA patients at TCZ initiation and during treatment follow-up. A difference of 0.5 log10 or of threefold copies/mL between two VL was considered significant.

Results: There were 20 (91%) women, (mean age of 57.8±11.2 years, mean disease duration 11.3±9.7 years) with 16 (73%) seropositive and 16 (73%) erosive patients. TCZ was administered alone for 8 patients (36.7%) or in combination with methotrexate for 11 patients (50%). At baseline, the EBV VL was positive in 8 patients with a mean VL value of 1777.2±3518.3 (3.5±0.4 log10) copies/mL. Only one patient had a positive CMV VL with 2337 copies/mL (3.4 log10). The VZV VL was negative in all patients. After 9.2±4.8 months, EBV VL became negative in 6 of 8 patients (P=0.01) and did not significantly vary in the remaining 2 patients. CMV VL became also negative. No VL (EBV, CMV, VZV) became positive. A positive EBV VL did not correlate with disease activity or with inflammatory biomarkers (ESR and CRP).

Conclusion: TCZ does not seem to increase the VL of EBV, CMV or VZV. Studies involving larger patient populations are necessary.

Keywords: Cytomegalovirus (CMV); Epstein-Barr virus (EBV); Rheumatoid arthritis (RA); Tocilizumab; Varicella-zoster virus (VZV); Viral load.