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Abstract Background To get insight in the prevalence of high, or low/no serum infliximab trough levels in patients with low disease activity and if serum trough levels are stable and reliable longitudinally we conducted a prospective cohort study Methods In a longitudinal, observational cohort of RA patients treated with infliximab for at least 6 months, treatment interval, DAS28, infliximab trough levels and anti-infliximab antibodies were assessed. Prevalence of low (5 mg/l) infliximab serum trough levels and anti-infliximab antibodies was recorded. Relationship of a change in anti-infliximab antibodies and treatment interval was described. Reliability of consecutive infliximab serum trough levels and anti-infliximab antibodies in patients with stable DAS28 and treatment was analysed with Spearman correlation and kappa-analysis. Results 147 patients with a mean disease duration of 11 years (sd7) and DAS28 of 3.5 (sd1.3) at baseline were followed during 1.5 years. Inter-individual variability in infliximab levels in patients with low DAS28 was high (median 1.4 mg/L, IQR 3.35), with 31% (95%CI: 20-42%) having low (5 mg/L). Interestingly also in RA patients with DAS28 ≤ 3.2, anti-infliximab antibodies were found in one-third of the patients, with half of them having antibodies every visit during a median of more than one year. Agreement for consecutive measurements of serum trough levels and anti-infliximab antibodies was high in stable patients: r = 0.97 (p = 0.00001) and kappa = 1.0 (SE 0.14) Anti-infliximab antibody appearance was influenced by interval increases (relative risk (RR) 5.2, 2.6-10.7), but patients still showed low infliximab levels. Conclusions Low (and high) infliximab serum trough levels are prevalent, interestingly also in patients with low disease activity. Consecutive measurements of serum trough levels and anti-infliximab antibodies are reliable in stable patients. These test could be used to lower or stop infliximab in selected patients.

Abstract Background This study in patients with rheumatoid arthritis (RA) treated with infliximab describes prospectively the course of (anti)infliximab levels within an infusioncycle to assess at what moment patients develop low/no infliximab trough levels and/or detectable anti-infliximab levels. Methods Infliximab treated RA patients were included in this descriptive open-label cohort study. During one infusioncycle (anti-)infliximab levels were assessed just before and one hour after infusion, and subsequently at 50%, 75% and at the end of the infusioncycle (pre-infusion). Results 27 patients were included. The median infliximab levels decreased from 77.0 mg/l (p25-p75: 65-89) one hour after the infusion to pre-infusion levels of 0.0 mg/l (p25-p75: 0.0-3.1). In 7 (26%) patients pre-infusion anti-infliximab antibodies were detected; these antibodies were already present halfway through the infusioncycle in 5 of the 7 individuals. Patients with detectable pre-infusion anti-infliximab antibodies have significantly more often low/no infliximab levels (< 1 mg/l) halfway trough the infusioncycle (in 5/7 patients) compared to patients without detectable pre-infusion anti-infliximab antibodies (0/20 patients, p < 0.001). Conclusions Most anti-infliximab forming patients have detectable anti-infliximab antibodies halfway through an infusioncycle, which implies that these patients are exposed to nontherapeutical infliximab levels during more than halve of their infusion cycle. As none of the patients without anti-infliximab antibodies had no/low-infliximab levels halfway through the infusioncycle, the presence of pre-infusion anti-infliximab antibodies seems a sensitive and specific predictor for no/low infliximab-levels