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

Tsutomu Takeuchi, Nobuyuki Miyasaka, Yoshihiko Tatsuki, Toshiro Yano, Toru Yoshinari, Tohru Abe, Takao Koike

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)1208-1215
Number of pages8
JournalAnnals of the Rheumatic Diseases
Volume70
Issue number7
DOIs
Publication statusPublished - 2011 Jul

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Rheumatoid Arthritis
Tumor Necrosis Factor-alpha
Plasmas
Therapeutics
Infliximab
Methotrexate
Refractory materials
C-Reactive Protein
Serum
Limit of Detection
Joints

ASJC Scopus subject areas

  • Rheumatology
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Allergy

Cite this

Baseline tumour necrosis factor alpha levels predict the necessity for dose escalation of infliximab therapy in patients with rheumatoid arthritis. / Takeuchi, Tsutomu; Miyasaka, Nobuyuki; Tatsuki, Yoshihiko; Yano, Toshiro; Yoshinari, Toru; Abe, Tohru; Koike, Takao.

In: Annals of the Rheumatic Diseases, Vol. 70, No. 7, 07.2011, p. 1208-1215.

Research output: Contribution to journalArticle

Takeuchi, Tsutomu ; Miyasaka, Nobuyuki ; Tatsuki, Yoshihiko ; Yano, Toshiro ; Yoshinari, Toru ; Abe, Tohru ; Koike, Takao. / Baseline tumour necrosis factor alpha levels predict the necessity for dose escalation of infliximab therapy in patients with rheumatoid arthritis. In: Annals of the Rheumatic Diseases. 2011 ; Vol. 70, No. 7. pp. 1208-1215.
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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.",
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AU - Yano, Toshiro

AU - Yoshinari, Toru

AU - Abe, Tohru

AU - Koike, Takao

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