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Arthritis Research & Therapy

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Open Access 01-12-2016 | Research article

Early changes in blood-based joint tissue destruction biomarkers are predictive of response to tocilizumab in the LITHE study

Authors: Anne C. Bay-Jensen, Adam Platt, Anne Sofie Siebuhr, Claus Christiansen, Inger Byrjalsen, Morten A. Karsdal

Published in: Arthritis Research & Therapy | Issue 1/2016

Abstract

Background

Rheumatoid arthritis (RA) is characterized by gradual joint destruction. Tocilizumab (TCZ) significantly suppresses symptoms, however not all patients are protected from joint damage. We investigated whether early measurement of specific biomarkers could predict early joint protection response to tocilizumab.

Method

Serum biomarkers (CRPM, VICM, C1M, C2M, C3M (MMP-degraded CRP, vimentin type I, II and III collagen), CTX-I/OC (bone turnover), and CRP) were measured in 740 RA patients (the LITHE study) treated with Placebo, or 4 or 8 mg/kg TCZ. Early responders were those with ≥20 % improvement in SJC or TJC by week 16. The biomarkers' predictability of response was investigated by AUROC and classification regression tree analysis.

Results

The best biomarker predictability for identification of TCZ responders were; baseline CTX-I/OC (AUC 0.66, p = 0.0005) and changes in C1M (AUC 0.67, p = 0.0072), C2M (AUC 0.72, p = 0.0002), C3M (AUC 0.63, p = 0.018) and the combination of biomarkers (AUC 0.81, p = 0.0025). Patients with high bone turnover (CTX-I/OC) and low C2M were 6.8-fold (p = 0.003) more likely to have an early response to TCZ.

Conclusion

This enhanced pharmacodynamic (PD) response enabled identification of early responders with a superior TCZ clinical benefit. This biomarker model may assist in the identification of TCZ responsive RA patients and thus potentially benefit individual patients.

Trial registration

Clinicaltrials.gov: NCT00106535. JAN 2005

Available only for authorised users

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Title: Early changes in blood-based joint tissue destruction biomarkers are predictive of response to tocilizumab in the LITHE study
Authors: Anne C. Bay-Jensen
Adam Platt
Anne Sofie Siebuhr
Claus Christiansen
Inger Byrjalsen
Morten A. Karsdal
Publication date: 01-12-2016
Publisher: BioMed Central
Published in: Arthritis Research & Therapy / Issue 1/2016
Electronic ISSN: 1478-6362
DOI: https://doi.org/10.1186/s13075-015-0913-x

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