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.
RCT Entities:
OBJECTIVE: To determine the safety and pharmacokinetics of recombinant humantumornecrosis 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.
Authors: D E Furst; F C Breedveld; J R Kalden; J S Smolen; C E Antoni; J W J Bijlsma; G R Burmester; B Cronstein; E C Keystone; A Kavanaugh; L Klareskog Journal: Ann Rheum Dis Date: 2002-11 Impact factor: 19.103
Authors: D E Furst; F C Breedveld; J R Kalden; J S Smolen; G R Burmester; M Dougados; P Emery; A Gibofsky; A F Kavanaugh; E C Keystone; L Klareskog; A S Russell; L B A van de Putte; M H Weisman; A F Kavenaugh Journal: Ann Rheum Dis Date: 2003-11 Impact factor: 19.103
Authors: D E Furst; F C Breedveld; J R Kalden; J S Smolen; G R Burmester; P Emery; E C Keystone; M H Schiff; P L C M van Riel; M E Weinblatt; M H Weisman Journal: Ann Rheum Dis Date: 2006-11 Impact factor: 19.103
Authors: D E Furst; F C Breedveld; J R Kalden; J S Smolen; G R Burmester; J Sieper; P Emery; E C Keystone; M H Schiff; P Mease; P L C M van Riel; R Fleischmann; M H Weisman; M E Weinblatt Journal: Ann Rheum Dis Date: 2007-11 Impact factor: 19.103
Authors: Y Chernajovsky; A Annenkov; C Herman; K Triantaphyllopoulos; D Gould; H Dreja; S P Moyes; J L Croxford; R A Mageed; O L Podhajcer; D Baker Journal: Drugs Aging Date: 1998-01 Impact factor: 3.923