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Could toll-like receptors provide a missing link in chronic inflammation in rheumatoid arthritis? Lessons from a study on human rheumatoid tissue

journal contribution
posted on 2023-06-08, 12:39 authored by Sandra SacreSandra Sacre, Stefan K Drexler, Evangelos Andreakos, Marc Feldmann, Fionula M Brennan, Brian M J Foxwell
In the last decade the development of a number of biological therapies has revolutionised the treatment of rheumatic diseases. The first and most widely used of these approaches, tumour necrosis factor (TNF) blockade (infliximab, entanercept, adalimumab), has now been administered to over a million patients. However, the success of these biological therapies has also highlighted their limitations. None of these treatments has shown a 100% patient response; normally responses are in the 50-70% range. As proteins, these drugs cannot be given orally and they are expensive to produce, a cost ultimately borne by the patient/health provider that can seriously limit the availability of these drugs. Lastly, these treatments, whether involving the systemic neutralisation of a cytokine (eg, TNF or IL6 receptor blockade (tocilizumab)), the ablation of a B cell population (anti-CD20, rituximab), or the potential disruption of important cellular interactions as with CTLA4-Ig (abatacept), can cause major perturbations of the immune system, the long-term effects of which are still unclear. At present, treatments such as TNF blockade can result in an increased infectious risk and the reactivation of tuberculosis can be a major issue in certain populations. As with all therapies, there is an increasing large refractory population over time. Therefore, despite the undoubted success of these therapies, there is room for improvement. Although it might be too much to expect any new treatment to affect a "cure" (all the current biological therapies require repeated administrations), there are definite gains to be made in terms of cost, oral bioavailability and a more selective interference with the immune-inflammatory response.

History

Publication status

  • Published

Journal

Annals of the Rheumatic Diseases

ISSN

0003-4967

Publisher

BMJ Publishing Group

Volume

66 Sup

Page range

iii81-iii86

Department affiliated with

  • Clinical and Experimental Medicine Publications

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2012-11-01

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