Objective: To determine the safety and pharmacokinetics of recombinant human tumor necrosis factor receptor (p80) fusion protein (rhTNFR:Fc) administered as a single intravenous (iv) loading dose followed by subcutaneous (sc) maintenance injections twice weekly for one month in patients with refractory rheumatoid arthritis (RA).
Methods: Four dose groups were evaluated with 4 patients with RA per group: 3 received active drug and one received placebo injection. After each dose group completed 4 weeks of treatment, the patient who received placebo was allowed to receive the active drug for one month. After these 16 patients completed the study, 3 additional patients received the highest dose and 3 additional patients received the lowest dose in an open label study to obtain more safety data (total of 22 patients treated).
Results: There were no serious adverse effects. Drug related events include mild injection site reactions in 4 patients that did not necessitate discontinuation of the drug. There was no clearcut dose response among the treatment groups. At Week 4, there was 45% mean improvement in total pain and total joint scores in patients receiving active drug (n = 12), compared to 22% mean improvement in patients receiving placebo (n = 4). C-reactive protein (CRP) levels decreased substantially in patients treated with drug compared to placebo, 30 vs 13%, respectively. The decrease in CRP was most pronounced in the highest dose group.
Conclusion: This initial experience with rhTNFR:Fc fusion protein in RA justifies further evaluation of this agent in a larger placebo controlled trial.