Rheumatoid Arthritis: Sopwith M

Choy EH, Hazleman B, Smith M, Moss K, Lisi L, Scott DG, Patel J, Sopwith M, Isenberg DA. · Academic Department of Rheumatology, GKT School of Medicine, King's College London, King's College Hospital, London, UK. · Rheumatology (Oxford). · Pubmed #12364632 links to  free full text

Abstract: OBJECTIVE: 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.

Choy EH, Rankin EC, Kassimos D, Vetterlein O, Garyfallos A, Ravirajan CT, Sopwith M, Eastell R, Kingsley GH, Isenberg DA, Panayi GS. · Department of Clinical and Molecular Rheumatology, The Guy's Hospital Medical and Dental School, London, United Kingdom. · J Rheumatol. · Pubmed #10555883 No free full text.

Abstract: OBJECTIVE: We investigated the effect of an engineered human anti-tumor necrosis factor-alpha antibody, CDP571, on immune functions as well as bone and cartilage turnover in patients with rheumatoid arthritis (RA) in a placebo controlled trial. We also assessed the effects of repeated treatment with CDP571 in an open label continuation study. METHOD: Thirty-six patients were treated with either placebo or 0.1, 1, or 10 mg/kg of CDP571 given as an intravenous infusion. The followup period was 8 weeks. Lymphocyte phenotype, soluble CD4 (sCD4), soluble interleukin 2 receptor (sIL-2R), IL-6, and stromelysin levels in the blood were measured before and after treatment; bone and cartilage markers (pyridinoline, deoxypyridinoline, N-terminal telopeptide) were similarly assessed in the urine. Patients who completed a placebo controlled trial of CDP571 were offered further treatment with CDP571. They received a maximum of 2 further doses of 1 mg/kg (7 patients) or 10 mg/kg (9 patients) in an open study. RESULTS: Plasma IL-6 level was statistically significantly reduced in the 1 and 10 mg/kg groups. In the 10 mg/kg group, there were also reductions in plasma stromelysin and urine bone markers, although there was no change in sCD4 and sIL-2R levels. Repeat doses of CDP571 were well tolerated and continued to suppress the acute phase response and disease activity. CONCLUSION: Treatment with 10 mg/kg of CDP571 reduced IL-6 and surrogate markers of bone turnover in RA, suggesting that CDP571 might prevent joint damage in RA. Since there was no effect on lymphocyte markers despite the marked reduction in inflammation, CDP571 appears to have no effect on ongoing CD4 T cell activation.