Chimeric anti-tumor necrosis factor-alpha monoclonal antibody treatment ofpatients with rheumatoid arthritis receiving methotrexate therapy

Objective. To evaluate the safety and efficacy of single and multiple doses of a chimeric anti-TNF-a monoclonal antibody (infliximab) in patients with rheumatoid arthritis (RA) who had active disease despite therapy with meth otrexate (MTX). Methods. Twenty-eight patients with active RA despite receiving therapy wit h 10 mg/week of MTX were randomized to receive a single, blinded infusion o f either placebo or 5, 10, or 20 mg/kg infliximab. Twenty-three patients wh o completed the blinded study entered an open, multiple dose extension stud y in which they received up to 3 additional infusions of 10 mg/kg inflixima b at Weeks 12, 20, and 28. Safety, efficacy, and pharmacokinetics were eval uated during the blinded and open trial. Results. There were no serious infusion related reactions. In the blinded p hase, 17 (81.0%) of 21 patients receiving infliximab achieved an American C ollege of Rheumatology (ACR) 20% response at some point during the 12 weeks of followup compared to one (14.3%) of 7 patients receiving placebo (p = 0 .003). Clinical improvement was evident by the first week and was sustained through Week 12. For the 19 patients who received infliximab during the bl inded pant of the trial and continued into the open label trial, 53% mainta ined an ACR 20% response with multiple infusions of 10 mg/kg infliximab thr ough Week 40. Three patients withdrew from the trial during the open contin uation phase because of adverse events: cellulitis, infusion related dizzin ess and headache, and vasculitic rash. Infliximab in doses of 5 to 20 mg/kg had a mean terminal half-life ranging from 9 to 12 days and was detectable in sera from most patients 8 to 12 weeks after dosing. Conclusion. Infliximab is generally well tolerated during 40 weeks of thera py. A single infusion of 5 to 20 mg/kg infliximab significantly decreases t he signs and symptoms of RA compared to placebo in patients with active dis ease receiving MTX. Multiple doses of infliximab produce sustained clinical benefit for up to 40 weeks.