Elsevier

The Lancet

Volume 344, Issue 8930, 22 October 1994, Pages 1105-1110
The Lancet

Articles
Randomised double-blind comparison of chimeric monoclonal antibody to tumour necrosis factor α (cA2) versus placebo in rheumatoid arthritis

https://doi.org/10.1016/S0140-6736(94)90628-9Get rights and content

Abstract

Summary

Tumour necrosis factor α (TNFα) 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 TNFα (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.

References (27)

  • M. Feldmann et al.

    Does TNFα have a pivotal role in the cytokine network in rheumatoid arthritis?

  • Rn Maim et al.

    TNFα in rheumatoid arthritis and prospects of anti-TNF therapy

    Clin Exp Rheumatol

    (1993)
  • Mj Elliott et al.

    Treatment of rheumatoid arthritis with chimaeric monoclonal antibodies to tumour necrosis factor &agr

    Arthritis Rheum

    (1993)
  • Cited by (1692)

    • Rheumatoid arthritis

      2024, Inflammopharmacology
    View all citing articles on Scopus
    View full text