Objectives To investigate the possible role of baseline plasma tumour necrosis factor alpha levels (baseline-TNF) on the clinical response to infliximab in patients with rheumatoid arthritis (RA).
Methods Patients with RA refractory to methotrexate received 3, 6, or 10 mg/kg of infliximab every 8 weeks, in a randomised, double-blind manner: the RISING study. Clinical response (disease activity score in 28 joints based on C-reactive protein or American College of Rheumatology core set) at week 54 and serum infliximab levels were compared in three patient groups with low, intermediate, or high baseline-TNF (TNF-low, TNF-int, or TNF-high).
Results In TNF-low patients, the clinical response to different doses of infliximab was comparable, whereas TNF-int patients exhibited a dose-dependent trend. In contrast, TNF-high patients (approximately 13% of the total patients) had a clinical response to 10 mg/kg significantly better than the response to 3 and 6 mg/kg of infliximab. In TNF-high patients, the median trough serum levels of infliximab were below the detection limit (<0.1 μg/ml) at 3 and 6 mg/kg but were greater than 2 μg/ml at 10 mg/kg, whereas the levels were approximately 1 μg/ml for each dosage group in TNF-low patients.
Conclusion In patients with RA, baseline-TNF is significantly associated with the clinical response to infliximab in patients with a high baseline-TNF. A higher dose of infliximab may be necessary in these patients, whereas lower doses of infliximab are sufficient for those with a low baseline-TNF. Baseline-TNF may be a useful measure for personalising the treatment of RA using infliximab.
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Funding Mitsubishi Tanabe Pharma Corporation sponsored this clinical trial and was responsible for the collection and analysis of data. The authors and the sponsor were involved with study design and the interpretation of data. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit the report for publication.
Competing interests TT and NM have received research support and consulting or lecture fees from Mitsubishi Tanabe Pharma Corporation. YT, TY and TY are employees of Mitsubishi Tanabe Pharma Corporation. TA and TK have received consulting and lecture fees from Mitsubishi Tanabe Pharma Corporation.
Patient consent Obtained.
Ethics approval The study protocol was approved by the local institutional review board and was carried out in accordance with the Helsinki Declaration and good clinical practice.
Provenance and peer review Not commissioned; externally peer reviewed.
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