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Rheumatoid Arthritis: An Evolutionary Force in Biologics

Lookup NU author(s): Dr Philip Brown, Professor John IsaacsORCiD

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Abstract

The advent of biologic therapy has transformed the outcomes of patients with Rheumatoid Arthritis (RA), but has also highlighted important issues for their development. Early attempts at T-cell driven therapies gave mixed results with difficulties extrapolating from non-human models to first in man trials. There is currently one T-cell modulating therapy - abatacept - licenced for use in RA. Cytokine inhibition has proven to be more fruitful with a number of anti-TNF and IL6 agents either licenced for use in RA or in development. The B-cell depleting therapy rituximab has also shown good efficacy as a chemotherapy agent repurposed for RA treatment.Overall the biologics show good efficacy in RA and have been shown to retard progression of radiographic joint damage. However, this benefit comes with a burden of increased infection risk and a financial cost significantly higher than conventional disease modifying therapies. As a result current UK licencing holds the biologics in reserve following failure of a conventional therapy and the presence of moderate to severely active disease.The long term use of the biologics in RA has highlighted the risk of immunogenicity, with significant proportions of patients developing anti-drug antibodies and losing therapeutic effect. The side effect profile and cost also raise the question around duration of therapy and trials of drug tapering following disease remission are now taking place with several biologic agents. Our inability to stratify patients to the most appropriate biologic drug (stratified or precision medicine) has also catalysed a large and critically important research agenda. Beyond identifying new biologic targets, the development of biosimilar agents will likely drive the future shape of the RA biologics market as lower cost alternatives are developed, thereby improving access to these therapies.


Publication metadata

Author(s): Brown PM, Isaacs JD

Publication type: Article

Publication status: Published

Journal: Current Pharmaceutical Design

Year: 2015

Volume: 21

Issue: 17

Pages: 2170-2178

Print publication date: 01/01/2015

Acceptance date: 01/01/1900

ISSN (print): 1381-6128

ISSN (electronic): 1873-4286

Publisher: Bentham Science Publishers Ltd.

URL: http://dx.doi.org/10.2174/1381612821666150310141827

DOI: 10.2174/1381612821666150310141827

PubMed id: 25760301


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