Baseline tumour necrosis factor alpha levels predict the necessity for dose escalation of infliximab therapy in patients with rheumatoid arthritis.
Author(s): Takeuchi T, Miyasaka N, Tatsuki Y, Yano T, Yoshinari T, Abe T, Koike T
Affiliation(s): Division of Rheumatology, Department of Internal Medicine, School of Medicine, Keio University, Shinjuku-ku, Tokyo, Japan. email@example.com
Publication date & source: 2011-07, Ann Rheum Dis., 70(7):1208-15. Epub 2011 Apr 8.
Publication type: Randomized Controlled Trial; Research Support, Non-U.S. Gov't
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 mug/ml) at 3 and 6 mg/kg but were greater than 2 mug/ml at 10 mg/kg, whereas the levels were approximately 1 mug/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.