Dose Escalation of Infliximab Is Helpful in Active Rheumatoid Arthritis

In patients with active rheumatoid arthritis (RA), dose escalation of infliximab is associated with more than 20% improvement in tender and swollen joint count, according to the results of a study published in the June 1 Online First issue of the Annals of the Rheumatic Diseases.
"The recommended dosage of infliximab for RA is an induction regimen of 3 mg/kg followed by maintenance dosing every 8 weeks," write Mahboob U. Rahman, and colleagues. "For patients with an incomplete response to 3 mg/kg infliximab, the product labelling for the United States allows for increasing the dose up to 10 mg/kg or reducing the interval between infusions to 4 weeks. Recent retrospective studies of governmental and private medical insurance databases, registries and medical records indicate that dose escalation of infliximab in patients with an inadequate response is not uncommon in actual clinical practice."
In 1 of the 3 groups of the Safety Trial for Rheumatoid Arthritis with Remicade Therapy (START), patients with RA that was still active after treatment with methotrexate received 3 mg/kg of infliximab at weeks 0, 2, 6, and 14. Beginning at week 22, the infliximab dose was increased in a double-blind fashion in increments of 1.5 mg/kg if the total tender and swollen joint count did not improve by at least 20% from baseline (criterion for lack of response) or if the improvement at week 22 or later worsened by 50% or more (criterion for flare).
Of the 329 patients eligible for dose escalation, 100 (30.4%) required dose escalation at or after week 22 because of flare or lack of response. After their last dose escalation, most patients (80%) who received up to 3 dose escalations had more than 20% improvement in the total tender and swollen joint count. Compared with patients who did not require dose escalations, those who did generally had lower preinfusion serum infliximab concentrations. Rates of adverse events and serious adverse events were similar for the patients who received dose escalation(s) compared with those who did not receive dose escalation.
Study limitations include lack of data on Clinical Disease Activity Index scores and 1-year study duration.
"Fewer than one-third of patients required a dose escalation," the authors write. "The majority of patients showed improvement after receiving increased doses of infliximab, without an increased risk of adverse events."
Centocor Research and Development Inc funded this study and employs 4 of its authors. Some other authors have disclosed various financial relationships with Johnson and Johnson, Inc, Schering-Plough Belgium, Bristol-Myers Squibb, Abbott, Centocor, and/or Genentech.
Ann Rheum Dis. Published online June 1, 2007.