Rheumatology 2002; 41: 1133-1137
© 2002 British Society for Rheumatology
Original Papers |
Efficacy of a novel PEGylated humanized anti-TNF fragment (CDP870) in patients with rheumatoid arthritis: a phase II double-blinded, randomized, dose-escalating trial
GKT School of Medicine, King's College London, London
1 Addenbrooke's NHS Trust Hospital, Cambridge
2 University College London, London
3 Norfolk and Norwich Hospital, Norwich and
4 Celltech Research and Development, Slough, UK
Objective. Biological products that neutralize tumour necrosis factor 
(TNF-) are beneficial in rheumatoid arthritis (RA). We studied the effects of CDP870, a novel anti-TNF- antibody fragment modified to obtain a prolonged plasma half-life (
14 days).
Methods. Thirty-six patients were randomized in a double-blind, ascending-dose group study to a single intravenous infusion of placebo (n = 12) or 1, 5 or 20 mg/kg CDP870 (each n = 8). The patients were predominantly female (30/36), had a mean age of 56 yr and a mean duration of RA of 13 years. They had received a mean of five DMARDs or experimental therapies (with 1 month washout before the study started) and had active disease. Continuation of NSAIDs and up to 7.5 mg prednisolone daily was allowed. Following the blinded dosing period, 32 patients received a single open-label infusion of either 5 or 20 mg/kg CDP870.
Results. In the blinded dosing period, 6/12 placebo patients withdrew from the study (for deteriorating RA 
4 weeks after dosing). Two of 24 CDP870-treated patients withdrew, both in the 1 mg/kg group (for deteriorating RA or lost to follow up >4 weeks after dosing). The proportion of patients with ACR20 improvement for the per-protocol population with the last observation carried forward was 16.7, 50, 87.5 and 62.5% after 0, 1, 5 and 20 mg/kg CDP870 respectively (combined treatment effect, P = 0.012, primary analysis) at 4 weeks and 16.7, 25, 75 and 75% (P = 0.032) at 8 weeks. The proportion of patients with ACR50 improvement for the per-protocol population with the last observation carried forward was 0, 12.5, 12.5 and 50% after 0, 1, 5 and 20 mg/kg CDP870 respectively (combined treatment effect, P = 0.079) at 4 weeks and 0, 12.5, 12.5 and 50% (P = 0.079) at 8 weeks. Following the open-label dose of CDP870, similar beneficial effects were achieved.
Conclusion. CDP870 is effective, was very well tolerated in this small study, and has an extended duration of action following one or more intravenous doses.
KEY WORDS: Rheumatoid arthritis, Immunotherapy, Biologicals, Monoclonal antibodies, Tumour necrosis factor, Polyethylene glycol.
Correspondence to: E. Choy, Academic Department of Rheumatology, GKT School of Medicine, King's College Hospital (Dulwich), East Dulwich Grove, London SE22 8PT, UK.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A. Kuek, B. L Hazleman, and A. J K Ostor Immune-mediated inflammatory diseases (IMIDs) and biologic therapy: a medical revolution Postgrad. Med. J., April 1, 2007; 83(978): 251 - 260. [Abstract] [Full Text] [PDF]
|
|