Baseline tumour necrosis factor alpha levels predict the necessity for dose escalation of infliximab therapy in patients with rheumatoid arthritis.

Abstract

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.

• Authors: Tsutomu Takeuchi, Nobuyuki Miyasaka, Yoshihiko Tatsuki, Toshiro Yano, Toru Yoshinari, Tohru Abe, Takao Koike
• Journal: Annals of the rheumatic diseases (Ann Rheum Dis) Vol. 70 Issue 7 Pg. 1208-15 (Jul 2011) ISSN: 1468-2060 [Electronic] England
• PMID: 21478189 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antirheumatic Agents
• Biomarkers
• Tumor Necrosis Factor-alpha
• Infliximab

Topics

• Adult
• Antibodies, Monoclonal (administration & dosage, blood, therapeutic use)
• Antirheumatic Agents (administration & dosage, blood, therapeutic use)
• Arthritis, Rheumatoid (blood, drug therapy)
• Biomarkers (blood)
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Epidemiologic Methods
• Female
• Humans
• Infliximab
• Male
• Middle Aged
• Treatment Outcome
• Tumor Necrosis Factor-alpha (antagonists & inhibitors, blood)