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Efficacy of a novel PEGylated humanized anti-TNF fragment (CDP870) in patients with rheumatoid arthritis: a phase II double-blinded, randomized, dose-escalating trial.

AbstractOBJECTIVE:
Biological products that neutralize tumour necrosis factor alpha (TNF-alpha) are beneficial in rheumatoid arthritis (RA). We studied the effects of CDP870, a novel anti-TNF-alpha antibody fragment modified to obtain a prolonged plasma half-life ( approximately 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 < or =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.
AuthorsE H S Choy, B Hazleman, M Smith, K Moss, L Lisi, D G I Scott, J Patel, M Sopwith, D A Isenberg
JournalRheumatology (Oxford, England) (Rheumatology (Oxford)) Vol. 41 Issue 10 Pg. 1133-7 (Oct 2002) ISSN: 1462-0324 [Print] England
PMID12364632 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial)
Chemical References
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Immunoglobulin Fab Fragments
  • Immunoglobulin Fragments
  • Tumor Necrosis Factor-alpha
  • Polyethylene Glycols
  • Certolizumab Pegol
Topics
  • Adolescent
  • Adult
  • Aged
  • Antibodies, Monoclonal (administration & dosage, adverse effects, blood)
  • Antibodies, Monoclonal, Humanized
  • Arthritis, Rheumatoid (therapy)
  • Certolizumab Pegol
  • Double-Blind Method
  • Humans
  • Immunoglobulin Fab Fragments
  • Immunoglobulin Fragments (administration & dosage, adverse effects, blood)
  • Middle Aged
  • Polyethylene Glycols (administration & dosage, adverse effects)
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha (immunology)

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