Randomised double-blind comparison of chimeric monoclonal antibody to tumour necrosis factor alpha (cA2) versus placebo in rheumatoid arthritis
| Autor: | M.J Elliott, R.N Maini, M Feldmann, J.R Kalden, C Antoni, J.S Smolen, B Leeb, F.C Breedveld, J.D Macfarlane, J.A Bijl, J.N Woody |
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| Jazyk: | angličtina |
| Rok vydání: | 1994 |
| Předmět: |
Adult
Male medicine.medical_specialty Adolescent medicine.medical_treatment Dose-Response Relationship Immunologic Arthritis Placebo Gastroenterology Arthritis Rheumatoid Placebos Double-Blind Method Internal medicine medicine Clinical endpoint Humans Adverse effect Infusions Intravenous Aged Pain Measurement business.industry Tumor Necrosis Factor-alpha Antibodies Monoclonal General Medicine Middle Aged medicine.disease Infliximab Cytokine Rheumatoid arthritis Antirheumatic Agents Immunology Tumor necrosis factor alpha Female business medicine.drug |
| Zdroj: | Lancet. 344(8930) |
| ISSN: | 1474-547X 0140-6736 |
| Popis: | Tumour necrosis factor alpha (TNF alpha) is a critical inflammatory mediator in rheumatoid arthritis, and may therefore be a useful target for specific immunotherapy. In support of this hypothesis, we previously observed beneficial responses in patients with active rheumatoid arthritis after open-label administration of a chimeric monoclonal antibody to TNF alpha (cA2). We now report the results of a four-centre, randomised double-blind trial of a single infusion of 1 or 10 mg/kg cA2 compared with placebo in 73 patients with active rheumatoid arthritis. The primary endpoint of the study was the achievement at week 4 of a Paulus 20% response, an amalgam of six clinical, observational, and laboratory variables. Intention-to-treat analysis of data from individual patients showed only 2 of 24 placebo recipients responding at this time, compared with 11 of 25 patients treated with low-dose cA2 (p = 0.0083) and 19 of 24 patients treated with high-dose cA2 (p < 0.0001). Over half of the high-dose cA2 patients responded by the more stringent 50% Paulus criteria at this time (p = 0.0005). The magnitude of these responses was impressive, with maximum mean improvements in individual disease-activity assessments, such as tender or swollen-joint counts and in serum C-reactive protein, exceeding 60% for patients on high-dose treatment. There were two severe adverse events. 1 patient on 1 mg/kg cA2 developed pneumonia ("possibly" treatment-related) and 1 on 10 mg/kg had a fracture ("probably not" treatment-related). The results provide the first good evidence that specific cytokine blockade can be effective in human inflammatory disease and define a new direction for the treatment of rheumatoid arthritis. |
| Databáze: | OpenAIRE |
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