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Abstract Number: 2335

Epstein-Barr Virus In Peripheral Blood Of Rheumatoid Arthritis Patients Predicts Response To Rituximab Therapy

Heikki Valleala1, Markku Korpela2, Markku J. Kauppi3 and Yrjo T. Konttinen4, 1Department of Medicine, Division of Rheumatology, Helsinki University Central Hospital, Helsinki, Finland, 2Department of Internal Medicine, Centre for Rheumatic Diseases, Tampere University Hospital, Tampere, Finland, 3Department of Internal Medicine, Päijät-Häme Central Hospital, Lahti, Finland, 4Dept of Medicine, Helsinki Univ Central Hospital, Helsinki, Finland

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: prognostic factors, Rheumatoid arthritis (RA), rituximab and viruses

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Session Information

Title: Rheumatoid Arthritis Treatment - Small Molecules, Biologics and Gene Therapy III

Session Type: Abstract Submissions (ACR)

Background/Purpose: Autoreactive B-cells infected by Epstein-Barr virus (EBV) are suspected to be involved in the aetiology of various human chronic autoimmune diseases. The aim of this study was to determine whether EBV load in the peripheral blood of  rheumatoid arthritis (RA) patients predicts response to B-cell depleting therapy with rituximab (RTX).     

Methods: 35 RA patients who started treatment with RTX in a routine clinical setting were recruited to this observational study between February 2010 and August 2011. At baseline, disease activity was assessed using DAS28 (ESR) and whole blood (WB) samples were collected to be stored at – 70oC. Treatment response was evaluated 3 – 7 months after RTX and if the patient had more than one visit the lowest DAS28 value was used for efficacy analysis. EBV viral load was assessed using quantitative PCR. Quantitative data are reported as median and range, and were compared using Mann-Whitney test. For qualitative data analysis Fisher’s exact test was used.

Results: The median disease duration was 16.0 (3-38) years. The number of prior biologicals was 2 (0-4) and the median number of failed synthetic DMARDs was 6 (2-9). 34/35 (97.1%) of the patients were RF positive and 26/27 (96.3%) anti-CCP positive. EBV DNA was detected in 16/35 (45.7%) of the WB samples collected prior to RTX treatment. In the 16 EBV positive patients the median viral load was 3.15 (2.68 – 4.00) log copies/ml. Good/moderate EULAR response was observed in 16/16 of the EBV DNA positive vs 13/19 EBV DNA negative patients, p = 0.022. Significant response (DAS28 change >1.2) was observed in 14/16 of the EBV DNA positive vs 10/19 EBV DNA negative patients, p = 0.035. The decline in DAS28 after RTX was 2.10 (1.03 – 4. 78) in the EBV DNA positive vs  1.47 (-0.7 – 4.70) in the EBV DNA negative patients, p = 0.13.  

Conclusion: Our results suggest that presence of EBV genome in WB predicts clinical response to B-cell depleting therapy with RTX. The results also putatively suggest that EBV may have an aetiopathogenic role in a subpopulation of RA patients. However, over 50 % of the EBV negative patients had a clinically significant response to RTX suggesting that, in addition to EBV, also other environmental triggers may be involved in the development of autoreactive B-cell clones.


Disclosure:

H. Valleala,
None;

M. Korpela,
None;

M. J. Kauppi,
None;

Y. T. Konttinen,
None.

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