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Therapeutic agents for patients with rheumatoid arthritis and an inadequate response to tumour necrosis factor-alpha antagonists

Lookup NU author(s): Professor John IsaacsORCiD


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Background: Rheumatoid arthritis (RA) is a disabling autoimmune disease; unless adequately controlled, patients have a poor long-term prognosis. Tumour necrosis factor (TNF)-alpha antagonists have provided relief for many RA patients; however, despite their efficacy, some patients do not respond or fail to maintain initial response. In the UK, patients with an inadequate response to TNF-alpha antagonists have limited options, as the National Institute of Clinical Excellence (NICE) currently only recommend switching to an alternative TNF-alpha antagonists if discontinuation occurs due to safety during the first 6 months of treatment. The EU has approved three biological agents, rituximab, abatacept, and to cilizumab, for patients with RA with an inadequate response to TNF-alpha antagonists. Objective: This review examines the clinical experience with two therapies targeting key immune cells involved in RA - rituximab (lyses B-cells), and abatacept (T-cell co-stimulation modulator) - specifically focusing on patients with an inadequate response to TNF-alpha blockade. Methods: Phase II/III clinical trials and original studies were identified using Medline and Pubmed; articles assessing the efficacy and/or safety of rituximab or abatacept in patients with RA refractory to TNF-alpha blockade were reviewed. Conclusions: Clinical data for rituximab and abatacept demonstrate that both reduce disease activity in TNF-a antagonist inadequate responders, suggesting that agents with alternative mechanisms of action, such as those targeting key immune cells, may be useful in this patient population.

Publication metadata

Author(s): Isaacs JD

Publication type: Review

Publication status: Published

Journal: Expert Opinion on Biological Therapy

Year: 2009

Volume: 9

Issue: 12

Pages: 1463-1475

ISSN (print): 1471-2598

ISSN (electronic): 1744-7682



DOI: 10.1517/14712590903379494