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Torque Teno Virus quantification for monitoring of immunomodulation with biologic compounds in the treatment of rheumatoid arthritis

P. Studenic, G. Bond, A. Kerschbaumer, M. Bécède, K. Pavelka, D. Karateev, J. Stieger, R. Puchner, RB. Mueller, E. Puchhammer-Stöckl, M. Durechova, M. Loiskandl, T. Perkmann, M. Olejarova, E. Luchikhina, CW. Steiner, M. Bonelli, JS. Smolen, D. Aletaha

. 2022 ; 61 (7) : 2815-2825. [pub] 20220706

Language English Country England, Great Britain

Document type Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc22025264

OBJECTIVES: RA patients who fail to respond to MTX can receive biologic dMARDs (bDMARDs). The Torque Teno Virus (TTV) is a potential novel candidate for monitoring of immunosuppression. We explore TTV in these patients and its association with clinical response to bDMARDs. METHODS: The BioBio Study is a multicentre randomized open-label trial, including RA patients with insufficient response to MTX. Patients were randomized to either TNFi (infliximab, INF), anti-IL-6 (tocilizumab, TCZ), CTLA4-Ig (abatacept, ABA) or anti-CD20 (rituximab, RTX) in addition to MTX. PCR was used to quantify TTV in the peripheral blood. RESULTS: TTV was measured in 95 patients (INF, n = 23; TCZ, n = 22; ABA, n = 27; RTX; n = 23). TTV increased by a median of 4.5 × 104 copies/ml [c/ml; interquartile range (IQR) 0-7.5 × 105] after 3 months. TTV levels at month 3 were associated with the Simplified Disease Activity Index (SDAI) (P = 0.03) and the Clinical Disease Activity Index (CDAI) response (P = 0.026) at month 6. A TTV cut-off level of 1.2 × 106 c/ml at month 3 had a positive likelihood ratio of 2.7 for prediction of an 85% reduction in SDAI at month 6. CONCLUSION: Our data suggest that TTV levels increase upon TNF, CD20 and costimulation blockade and are associated with the clinical response to bDMARDs in RA patients. TRIAL REGISTRATION: ClinicalTrials.gov; https://clinicaltrials.gov; NCT01638715.

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$a OBJECTIVES: RA patients who fail to respond to MTX can receive biologic dMARDs (bDMARDs). The Torque Teno Virus (TTV) is a potential novel candidate for monitoring of immunosuppression. We explore TTV in these patients and its association with clinical response to bDMARDs. METHODS: The BioBio Study is a multicentre randomized open-label trial, including RA patients with insufficient response to MTX. Patients were randomized to either TNFi (infliximab, INF), anti-IL-6 (tocilizumab, TCZ), CTLA4-Ig (abatacept, ABA) or anti-CD20 (rituximab, RTX) in addition to MTX. PCR was used to quantify TTV in the peripheral blood. RESULTS: TTV was measured in 95 patients (INF, n = 23; TCZ, n = 22; ABA, n = 27; RTX; n = 23). TTV increased by a median of 4.5 × 104 copies/ml [c/ml; interquartile range (IQR) 0-7.5 × 105] after 3 months. TTV levels at month 3 were associated with the Simplified Disease Activity Index (SDAI) (P = 0.03) and the Clinical Disease Activity Index (CDAI) response (P = 0.026) at month 6. A TTV cut-off level of 1.2 × 106 c/ml at month 3 had a positive likelihood ratio of 2.7 for prediction of an 85% reduction in SDAI at month 6. CONCLUSION: Our data suggest that TTV levels increase upon TNF, CD20 and costimulation blockade and are associated with the clinical response to bDMARDs in RA patients. TRIAL REGISTRATION: ClinicalTrials.gov; https://clinicaltrials.gov; NCT01638715.
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$a Bond, Gregor $u Division of Nephrology and Dialysis, Medical University of Vienna, Vienna, Austria $1 https://orcid.org/0000000304403053
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$a Kerschbaumer, Andreas $u Department of Internal Medicine 3, Division of Rheumatology, Medical University of Vienna, Vienna, Austria
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$a Bécède, Manuel $u Department of Internal Medicine 3, Division of Rheumatology, Medical University of Vienna, Vienna, Austria
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$a Pavelka, Karel $u Institute of Rheumatology $u Department of Rheumatology, First Faculty of Medicine, Charles University, Prague, Czech Republic
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$a Karateev, Dmitry $u Department of Rheumatology, Moscow Regional Research and Clinical Institute (MONIKI), Moscow, Russia
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$a Stieger, Jutta $u 2nd Department of Medicine, Hietzing Hospital, Vienna
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$a Puchner, Rudolf $u Rheumatologist in Private Practice, Wels, Austria
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$a Mueller, Ruediger B $u Cantonal Hospital Lucerne, Division of Rheumatology, Medical University Department, Rheumazentrum Ostschweiz, St. Gallen, Switzerland
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$a Puchhammer-Stöckl, Elisabeth $u Center of Virology
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$a Durechova, Martina $u Department of Internal Medicine 3, Division of Rheumatology, Medical University of Vienna, Vienna, Austria
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$a Loiskandl, Michaela $u Department of Internal Medicine 3, Division of Rheumatology, Medical University of Vienna, Vienna, Austria
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$a Perkmann, Thomas $u Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
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$a Olejarova, Martina $u Institute of Rheumatology $u Department of Rheumatology, First Faculty of Medicine, Charles University, Prague, Czech Republic
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$a Luchikhina, Elena $u Department of Rheumatology, Moscow Regional Research and Clinical Institute (MONIKI), Moscow, Russia
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$a Steiner, Carl-Walter $u Department of Internal Medicine 3, Division of Rheumatology, Medical University of Vienna, Vienna, Austria
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$a Bonelli, Michael $u Department of Internal Medicine 3, Division of Rheumatology, Medical University of Vienna, Vienna, Austria
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$a Smolen, Josef S $u Department of Internal Medicine 3, Division of Rheumatology, Medical University of Vienna, Vienna, Austria
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$a Aletaha, Daniel $u Department of Internal Medicine 3, Division of Rheumatology, Medical University of Vienna, Vienna, Austria $1 https://orcid.org/0000000321080030
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