title: Baseline tumour necrosis factor alpha levels predict the necessity for dose escalation of infliximab therapy in patients with rheumatoid arthritis.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.affiliation: Division of Rheumatology, Department of Internal Medicine, School of Medicine, Keio University, Shinjuku-ku, Tokyo, Japan. tsutake@z5.keio.jp
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Takeuchi
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Miyasaka
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Tatsuki
authors.forename: Toshiro
authors.initials: T
authors.lastname: Yano
authors.forename: Toru
authors.initials: T
authors.lastname: Yoshinari
authors.forename: Tohru
authors.initials: T
authors.lastname: Abe
authors.forename: Takao
authors.initials: T
authors.lastname: Koike
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy*; D015415:Biomarkers / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004812:Epidemiologic Methods; D005260:Female; D006801:Humans; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000097:blood*
chemical_list: D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D015415:Biomarkers; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab