Future Rheumatoid Arthritis Treatment Strategies โ€“ Improving Outcomes Using Predictors of Response

Paul P Tak, Gregg J Silverman, John D Isaacs, Andrea Rubbert-Roth, Gerd Burmester, John Isaacs
European Musculoskeletal Review, 2011;6(4): in press
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Abstract

Rheumatoid arthritis (RA) is a chronic disease with a complex pathogenesis. Recent therapeutic advances have seen the development of new biological therapies that target key participants in synovial inflammation, the hallmark of the disease. Predicting the clinical response of an individual patient to a given therapy will maximise patient outcomes, minimise safety concerns and enable the adoption of personalised medicine, as well as reducing treatment costs. However, because of the heterogeneity of the disease, definitive predictors of patient responses have yet to be clearly identified. Optimising therapy choice and determining which treatments are viable alternatives in the event of an inadequate clinical response is a dilemma for clinicians.

The satellite symposium โ€˜Future RA treatment strategies: improving outcomes using predictors of responseโ€™ presented at the European League Against Rheumatism (EULAR) 2011 annual meeting, aimed to address these issues, outlining current approaches used to inform treatment decisions and providing new perspectives on the optimisation of RA therapies for individual patients.
Keywords
Autoantibodies, B cell, biological therapy, personalised medicine, rheumatoid arthritis
Disclosure Paul P Tak has served as a consultant for Abbott, Amgen, BMS, MSD, Pfizer, and Roche/Genentech. Gregg J Silverman has been a consultant and member of the speaker board for Genentech and Roche. John Isaacs has consulted for Hoffman La Roche and Pfizer, and received speaker fees and research funding from Abbott Laboratories. Gregg J Silverman has served as an advisor or consultant for: Genentech, Inc.; Roche; Human Genome Sciences and as a speaker or a member of a speaker's bureau for: Genentech, Inc. Andrea Rubbert-Roth has received grants from Roche and Pfizer and honoraria for lectures from UCB, MSD, Pfizer, Amgen, BMS, and Roche and Chugai. Gerd Burmester has received scientific grants, honoraria for lectures and consultancies from Roche, Abbott, BMS, Pfizer, and UCB.
Received: September 18, 2011 Accepted September 28, 2011
Correspondence: Paul P Tak, Professor of Medicine, Div. Clinical Immunology and Rheumatology, F4-105, Academic Medical Center/University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. E: P.P.Tak@amc.uva.nl
Support: The publication of this article was supported by an independent educational grant from Roche. The views and opinions expressed are those of the authors and not necessarily those of Roche.

Traditional disease-modifying antirheumatic drugs (DMARDs), such as methotrexate (MTX), can provide effective treatment for rheumatoid arthritis (RA) when used as part of a tight control strategy with the aim of low disease activity or remission.1,2

In patients who fail to respond to MTX adequately, the addition of biological therapy, specifically the tumour necrosis factor (TNF) inhibitors adalimumab, etanercept, infliximab, golimumab or certolizumab, is recommended.3โ€“9 However, up to 60 % of patients do not achieve remission or low disease activity with their first TNF inhibitor10 and it is unclear whether the best therapeutic strategy for these patients is to try a second TNF inhibitor or to switch to a biologic with another mechanism of action.11,12

If patient responses to a given therapy could be predicted then this would help to optimise treatment strategies, maximise therapeutic outcomes whilst minimising adverse events and enable the adoption of personalised medicine for RA patients.13,14

The satellite symposium entitled โ€˜Future RA treatment strategies: improving outcomes using predictors of responseโ€™ at the 2011 European League Against Rheumatism (EULAR) annual meeting aimed to highlight how understanding the heterogeneity of RA pathogenesis and identifying predictors of response to current biologics can contribute to the selection of the most advantageous treatment strategy. Moreover, the value of using both efficacy and safety to inform treatment decisions was examined.

Finally, the impact of future treatment strategies on personalised medicine for RA treatment was discussed.

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