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

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.