Recombinant soluble tumor necrosis factor receptor (p80) fusion protein: toxicity and dose finding trial in refractory rheumatoid arthritis

J Rheumatol. 1996 Nov;23(11):1849-55.


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.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Arthritis, Rheumatoid / drug therapy*
  • Blood Sedimentation / drug effects
  • C-Reactive Protein / drug effects
  • Female
  • Humans
  • Male
  • Middle Aged
  • Receptors, Tumor Necrosis Factor*
  • Recombinant Fusion Proteins / immunology
  • Recombinant Fusion Proteins / pharmacology*
  • Treatment Outcome


  • Receptors, Tumor Necrosis Factor
  • Recombinant Fusion Proteins
  • C-Reactive Protein