Background/Purpose : There is a close association between serum Infliximab (Ifx) levels and the Antibodies To Infliximab (ATI) with the clinical activity in rheumatoid arthritis (RA) patients. Several markers have been described to predict the response to biological therapy but for now no evidence of serological markers during the TNFi therapy is available. Our aim was to analize whether Ifx drug levels at 2, 6 and 14 weeks after starting Ifx can predict the disappereance of serum Ifx levels and ATI detection at 6 months and 1 year in a cohort of RA patients treated with Ifx

Methods: 85 RA patients were included in this is ambispective observational study. The clinical activity was measured by DAS28 at baseline, 6 months and 1 year. The serum samples were obtained before each infusion at baseline, 2, 6 and 14 weeks after starting Ifx, 6 months and 1 year. Ifx and ATI levels were measured by ELISA. Receiver-operator characteristics (ROC) analysis were used to establish a cutt-off value for Ifx levels (2, 6 and 14 w) between patients with or without detectable Ifx levels at 6 months and 1 year. Area under the curve (AUC), sensitivity (S), specificity (SP) and positive likelihood ratio (LR+) were calculated at any studied point. The Last observation was carried forward (LOCF) for patients who dropped out before 1 year.

Results: Ifx levels at early stages (2, 6 and 14 weeks) of Ifx therapy were significantly lower in RA patients without detectable Ifx levels at 6 months and 1 year (Figure 1). Ifx levels lower than 21.2µg/ml at 2 weeks, 4.4µg/ml at 6 weeks and 0.4µg/ml at 14 weeks were predictive to Ifx disappearance at 6 months (2 weeks: AUC 0.708, S 67%, SP 87%, LR+5.1; 6 weeks: AUC 0.810, S 70%, SP 88%, LR+ 6.03; 14 weeks: AUC 0.923, S 83%, SP 92%, LR+10.4) and 1 year (2 weeks: AUC 0.708, S 64%, SP 89%, LR+5.8; 6 weeks: AUC 0.800, S 63%, SP 90%, LR+ 6.3; 14 weeks: AUC 0.923, S 75%, SP 94%, LR+13.1).

Conclusion: The monitoring of Ifx levels at early stages of therapy has a high value to discriminate which RA patients will have a faster Ifx clearance with the subsequent ATI detection and poor clinical outcomes. Patients with Ifx trough levels lower than 21.2, 4.4 and 0.4 µg/ml at 2, 6 and 14 weeks, respectively, have a high probability to develop ATI in the 1^st year under the therapy.