Shimaoka, T. response to 10 mg/kg considerably better than the response to 3 and 6 mg/kg of infliximab. In TNF-high individuals, the median trough serum levels of infliximab were below the detection limit ( 0.1 g/ml) at 3 and 6 mg/kg but were greater than 2 g/ml at 10 mg/kg, whereas the levels were approximately 1 g/ml for each dosage group in TNF-low patients. Conclusion In individuals with RA, baseline-TNF is definitely significantly associated with the medical response to infliximab in individuals with a high baseline-TNF. A higher dose of infliximab may be necessary in these individuals, whereas lower doses of infliximab are adequate for those with a low baseline-TNF. Baseline-TNF may be a useful measure for personalising the treatment of RA using infliximab. Rheumatoid arthritis (RA) is definitely a chronic, systemic inflammatory disease that results in joint damage and disability.1 Levels of tumour necrosis factor alpha (TNF), an inflammatory cytokine, are elevated in the blood and synovial fluid of individuals with RA, and may perform a central part in its pathogenesis.2C7 Although infliximab, an anti-TNF antibody, exhibits excellent performance in RA,8C11 insufficient response to the standard treatment of infliximab (3 mg/kg per 8 weeks) has also been observed in some instances in clinical practice. Such individuals are usually treated by dose escalation or by shortening the dose interval of the infliximab Rosabulin therapy.12C15 The RISING study (NCT00691028) is a randomised, Rabbit Polyclonal to OR10H2 double-blind clinical trial, which Rosabulin has shown the clinical response to infliximab at a dose of 10 mg/kg is significantly higher than the response to 3 mg/kg infliximab, and that a trough serum level of 1 g/ml is the threshold for clinical response.16 However, clinical response to different dose levels of infliximab was significant only for American College of Rheumatology (ACR) improvement criteria and the Western League Against Rheumatism (EULAR) responses, and the measurable difference was small. Several medical studies have attempted to address whether a higher dose of infliximab provides a better medical response than standard doses in individuals with RA.8C11 17 However, the results were not consistent among those studies. In addition, a randomised, double-blind study comparing dose escalation and continuation of the standard dose in individuals with RA who experienced an insufficient response to 3 mg/kg of infliximab clearly demonstrated no beneficial response by dose escalation,18 contrary to our results. Although the standard dose of infliximab can be efficacious in a large proportion of individuals with RA, some individuals may require a higher dose of infliximab to accomplish medical response.19 20 The inconsistent effects mentioned above might be explained by the different proportion of patients who might benefit from infliximab dose escalation in each study. Therefore the medical and immunological features of these individuals who require higher dose of infliximab are not fully recognized. It is appealing to speculate the production and resultant plasma levels of TNF, the prospective molecule of infliximab, exceeds the neutralising capacity of infliximab in insufficient responders who are unable to maintain the threshold serum level of infliximab. Considering that hypothesis, we analysed the RISING study data based on plasma TNF levels. We found that the medical response Rosabulin of individuals with high baseline levels of TNF (baseline-TNF) showed a significant improvement with higher doses of infliximab, whereas individuals with low baseline-TNF did not have a better response even with higher doses of infliximab. Methods Patients and study protocol The study protocol was authorized by the local institutional review table and was carried out in accordance with the Helsinki Declaration and good medical practice. Patient enrollment criteria and study design possess previously been explained in.