title: Open label study to assess infliximab safety and timing of onset of clinical benefit among patients with rheumatoid arthritis.
abstract: OBJECTIVE
  To assess the timing of onset of clinical benefit following the initial infusion of infliximab and to obtain additional safety experience of infliximab when given in an office setting to patients with rheumatoid arthritis (RA). In addition, the safety of reducing the infusion time from 2 hours to 1 hour was evaluated.
  
  
  METHODS
  Patients (n = 553) with active RA despite receiving methotrexate (MTX) were treated with infliximab 3 mg/kg given over 2 h at baseline (Week 0), and Weeks 2, 6, and 14 in this multicenter open-label trial. Patients continued to receive a stable dose of MTX (> or = 7.5 mg/wk). At selected sites, patients tolerating the first 4 infusions were eligible to receive 2 additional infusions at twice the usual infusion rate (given over 1 h). Patients returned for efficacy assessments at 48 h following the initial infusion and several times throughout study participation.
  
  
  RESULTS
  By 48 h following the first infusion, significant (p < 0.001) improvements were observed in duration of morning stiffness (34% mean improvement), physician's global disease assessment scores (30%), patient's global disease assessment scores (25%), and patient's pain assessment scores (30%). By Week 16, 52 to 63% mean improvements in these efficacy variables were observed (p < 0.001), the significant improvement was maintained through the end of study participation in the subset of patients who received the additional 1 h infliximab infusions. Through 16 weeks, 10% (54/553) of patients reported an adverse event associated with at least 1 of the 4 infusion procedures; the majority were mild and transient in nature. In the subset of 197 patients who received 2 additional infusions over 1 h, no increase in the frequency or severity of infusion-related adverse events was observed compared to the 2 h infusion.
  
  
  CONCLUSIONS
  Infliximab administered to patients with RA in an outpatient setting resulted in significant clinical improvement within 48 h that was sustained with additional infusions. Approximately 10% of patients experienced an infusion reaction, highlighting the need for direct supervision over patient treatment. Patients who tolerated infliximab infusions given over 2 h also tolerated a 1 h infusion.
authors.affiliation: Centocor Inc., Malvern, Pennsylvania, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Shergy
authors.forename: Reuben A
authors.initials: RA
authors.lastname: Isern
authors.forename: David A
authors.initials: DA
authors.lastname: Cooley
authors.forename: John L
authors.initials: JL
authors.lastname: Harshbarger
authors.forename: J Eugene
authors.initials: JE
authors.lastname: Huffstutter
authors.forename: Gordon M
authors.initials: GM
authors.lastname: Hughes
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Spencer-Smith
authors.forename: Allan L
authors.initials: AL
authors.lastname: Goldman
authors.forename: Sanford H
authors.initials: SH
authors.lastname: Roth
authors.forename: J Scott
authors.initials: JS
authors.lastname: Toder
authors.forename: Diana
authors.initials: D
authors.lastname: Warner
authors.forename: Adrienne
authors.initials: A
authors.lastname: Quinn
authors.forename: Gregory F
authors.initials: GF
authors.lastname: Keenan
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Schaible
mesh_terms: D000553:Ambulatory Care; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D000069285:Infliximab; D007262:Infusions, Intravenous / Q000009:adverse effects; D007596:Joints / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D010045:Outpatients; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D000069285:Infliximab; D008727:Methotrexate