BACKGROUND: Infliximab (IFX) can be immunogenic for humans and lead to the formation of antibodies against IFX (anti-IFX Ab), which could induce acquired IFX resistance. OBJECTIVE: To test whether the presence of anti-IFX Ab and residual circulating IFX levels are associated with acquired IFX resistance in RA. METHODS: A multivariate logistic regression was used to analyze the relationship between anti-IFX Ab, residual IFX concentrations, and acquired IFX resistance in a nested cohort within the Swiss RA registry (SCQM-RA). RESULTS: Sixty-four RA patients on longstanding IFX therapy were included; 24 with an acquired therapeutic resistance to IFX and 40 with continuous good response to IFX. The two groups had similar disease characteristics, but patients with acquired IFX resistance required significantly higher dosage of IFX (5.4 mg/kg versus 4.3 mg/kg, p=0.02) and shorter infusion intervals (7.1 versus 8.7 weeks, p=0.01) than long-term good responders. The presence of residual IFX tended to be associated with a decreased risk of acquired therapeutic resistance (OR 0.4 [95% CI: 0.1-1.5]), while the presence of anti-IFX Ab tended to be associated with an increased risk of acquired therapeutic resistance (OR: 1.8 [95% CI: 0.4 - 9.0]). The presence of either high anti-IFX Ab levels or low residual IFX concentrations was strongly associated with acquired therapeutic resistance to IFX (OR 5.9, 95% CI 1.3 - 26.6). However, just 42% of patients with acquired IFX resistance had either low IFX or high anti-IFX Ab levels. CONCLUSION: These results suggest that the assessment of anti-IFX Ab and residual IFX levels is of limited value for individual patients in routine clinical care.