IL-6 is an independent predictive factor of drug survival after dose escalation of infliximab in patients with rheumatoid arthritis

Objective: We aimed to investigate factors predictive of increased serum infliximab (IFX) concentration with improvement of disease activity, as well as better 1-year continuation rate after dose escalation, in patients with rheumatoid arthritis (RA) who showed inadequate response to 3mg/kg IFX.Methods: Among 42 patients allotted to receive 3mg/kg IFX, 13 patients showed adequate response (DAS28<3.2) and 29 patients required dose escalation to 4.5 or 6mg/kg after inadequate response (DAS283.2) to 3mg/kg IFX. DAS28, mHAQ, serum level of CRP, interleukin (IL)-6, IL-17, anti-infliximab antibody (AIA) titers and IFX concentration before and on average 2.7 months after dose escalation were examined to explore the baseline factors predictive of a clinically beneficial increase of serum IFX concentration and drug survival.Results: One year after IFX dose escalation, 25 patients completed the study protocol, and 16 patients (64%) continued to show a good response for one year, while 9 patients (36%) required switching of biologics because of inadequate response. Multivariate analyses revealed that a serum IL-6 level of less than 4.0pg/mL at baseline was the only factor predictive of a clinically beneficial increase of serum IFX concentration in patients who required dose escalation. Receiver operating characteristic analysis revealed that 5.16pg/mL of IL-6 was the cut-off value with sensitivity 0.833 and specificity of 0.769 (95%CI for AUC: 0.712-1.006). In patients with IL-6 levels of less than 5.16pg/mL at baseline, the serum IFX concentration significantly increased after dose escalation with adequate response. The 1-year drug survival rates of patients with IL-6 levels less than 5.16pg/mL and in those with levels greater than or equal to 5.16pg/mL at baseline were 83.3% and 30.8%, respectively (log-rank test, p=.011).Conclusions: The results of our study indicated that a baseline serum level of IL-6 below 5.16pg/mL might be a predictive factor for a clinically beneficial increase of serum IFX concentration with improvement of disease activity and better 1-year continuation rate after IFX dose escalation.