%0 Journal Article
%T Predictive Factors of Response to Biological Disease Modifying Antirheumatic Drugs: Towards Personalized Medicine
%A Claire I. Da£żen
%A Jacques Morel
%J Mediators of Inflammation
%D 2014
%I Hindawi Publishing Corporation
%R 10.1155/2014/386148
%X Many therapies are now available for patients with rheumatoid arthritis (RA) who have an inadequate response to methotrexate including tumor necrosis factor inhibitors, abatacept, tocilizumab, and rituximab. Clinical response to drugs varies widely between individuals. A part of this variability is due to the characteristics of the patient such as age, gender, concomitant therapies, body mass index, or smoking status. Clinical response also depends on disease characteristics including disease activity and severity and presence of autoantibodies. Genetic background, cytokine levels, and immune cell phenotypes could also influence biological therapy response. This review summarizes the impact of all those parameters on response to biological therapies. 1. Introduction Many biological therapies are now available for patients with rheumatoid arthritis (RA) who have an inadequate response to synthetic disease modifying antirheumatic drugs (sDMARD) especially methotrexate (MTX) or to a first tumor necrosis factor (TNF) inhibitor (TNFi). They can be treated with either TNFi (etanercept (ETN), infliximab (IFX), adalimumab (ADA), certolizumab, or golimumab), or a T cell targeting therapy (CTLA4-Ig abatacept (ABA)) or an anti-IL-6 receptor drug (tocilizumab (TCZ)), or a B cell targeting therapy, mostly represented by anti-CD20 antibodies like rituximab (RTX). Clinical response to drugs varies widely between individuals. A part of this variability is due to drug concentration and pharmacokinetic which is influenced by the characteristics of the patient such as age, gender, renal and liver functions, body mass index (BMI), or smoking status. Concomitant therapies and drug immunogenicity also influence drug concentrations. Clinical response depends on disease state and disease characteristics as well. Indeed, there are different subtypes of RA with different genetic backgrounds, that is, seropositive or seronegative RA [1] and benign or destructive RA [2¨C4]. Depending on patients, the RA could be preferentially mediated by one cytokine; for example, some diseases are very dependent on TNF, whereas others are not [5]. One immune cell type can also be more important in some patients than others (i.e., B or T cells, Th1 or Th17 [6], etc.). Although all these parameters may influence therapeutic response, tools which could be used in daily practice to predict response to biological drugs are lacking. This review synthesizes the largest studies on factors influencing response to TNFi, ABA, RTX, and TCZ therapy (Table 1). Table 1: Main studies presented in this review. 2.
%U http://www.hindawi.com/journals/mi/2014/386148/