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Emery P.,University of Leeds | Emery P.,NIHR Leeds Musculoskeletal Biomedical Research Unit | Dorner T.,Charite - Medical University of Berlin
Annals of the Rheumatic Diseases | Year: 2011

Following a greater understanding of the pathogenesis of rheumatoid arthritis (RA), the treatment of this chronic disease has improved with the availability of biological agents targeting key molecules. Despite this, initial treatment produces an inadequate response in many patients and guidance on the optimal treatment for these patients is needed. Research in specific patient populations aims to define predictive biomarkers of response to identify those patients most likely to benefit from treatment with specific agents. Although there have been conflicting results from studies of various genetic markers, single nucleotide polymorphisms in the tumour necrosis factor (TNF) -308 promoter region may play a role in response to specific TNF inhibitors. Microarray analysis of mRNA expression levels has identified unique sets of genes with differentially regulated expression in responders compared with non-responders to the TNF inhibitor infliximab. Of the various protein biomarkers studied, rheumatoid factor and/or anticitrullinated protein autoantibodies may have a future role in predicting response or guiding the order in which to use biological agents. Further research is needed with larger, well-designed studies to clarify the current understanding on the role of biomarkers in predicting treatment response in RA to help guide clinical decision-making. Individualised treatment has the potential to improve the therapeutic outcomes for patients.

Vital E.M.,NIHR Leeds Musculoskeletal Biomedical Research Unit | Kay J.,University of Massachusetts Medical School | Emery P.,University of Leeds
Expert Opinion on Biological Therapy | Year: 2013

Introduction: Rituximab is a monoclonal antibody targeting CD20, used to treat B cell malignancies and B cell-mediated autoimmune diseases. Rituximab has the largest market of any monoclonal antibody therapeutic. Its patent will expire within the next few years and several manufacturers have already produced or are developing rituximab biosimilars that aim to match the innovator rituximab as closely as possible. Areas covered: In this review, we discuss key factors that determine the efficacy of rituximab therapy, potential technical challenges in the manufacture and evaluation of biosimilars, regulatory considerations regarding the review and approval of biosimilars, and the current status of biosimilar rituximab development by various manufacturers. Due to the nature of the topic, literature searches included conference abstracts, regulatory and industry websites as well as peer reviewed literature. Expert opinion: Cost is a key limitation of current biologics usage and there is a political impetus to the licensing of biosimilars. Concerns regarding potential dissimilarities of biosimilars are legitimate, but surmountable with techniques for in vitro, in vivo and clinical testing and more clearly defined regulatory requirements. These should provide reassurance to prescribers. However, the cost of manufacturing and licensing a biosimilar remains high and the reduction in cost may be more limited than for a non-biologic small molecule drug and its generic version. This cost reduction will be critical to the impact and use of rituximab biosimilars. © 2013 Informa UK, Ltd.

Emery P.,University of Leeds | Emery P.,NIHR Leeds Musculoskeletal Biomedical Research Unit | Sebba A.,University of South Florida | Huizinga T.W.J.,Leiden University
Annals of the Rheumatic Diseases | Year: 2013

Clinical evidence demonstrates coadministration of tumour necrosis factor inhibitor (TNFi) agents and methotrexate (MTX) is more efficacious than administration of TNFi agents alone in patients with rheumatoid arthritis, leading to the perception that coadministration of MTX with all biologic agents or oral disease-modifying antirheumatic drugs is necessary for maximum efficacy. Real-life registry data reveal approximately one-third of patients taking biologic agents use them as monotherapy. Additionally, an analysis of healthcare claims data showed that when MTX was prescribed in conjunction with a biologic agent, as many as 58% of patients did not collect the MTX prescription. Given this discrepancy between perception and real life, we conducted a review of the peer-reviewed literature and rheumatology medical congress abstracts to determine whether data support biologic monotherapy as a treatment option for patients with rheumatoid arthritis. Our analysis suggests only for tocilizumab is there evidence that the efficacy of biologic monotherapy is comparable with combination therapy with MTX.

Hunt L.,University of Leeds | Emery P.,NIHR Leeds Musculoskeletal Biomedical Research Unit
Expert Opinion on Biological Therapy | Year: 2013

Introduction: Biologic agents have transformed clinical outcomes in rheumatoid arthritis, and there are now several immune-modulating therapies available. Tumour necrosis factor-α (TNF-α) inhibitors were the first biologic drug class licensed for the treatment of rheumatoid arthritis. Etanercept is a fusion protein composed of two TNF receptors bound to the constant portion (Fc) of human immunoglobulin G (IgG). Areas covered: This article will consider the pharmacological properties of etanercept and the clinical efficacy data presented in clinical trials. Its safety in clinical practice will be reviewed. Expert opinion: There is overwhelming evidence to support the use of etanercept in rheumatoid arthritis. Trial data demonstrate etanercept's efficacy in reducing structural damage, improving clinical outcomes and inducing remission. Optimal response to therapy is seen when used in combination with methotrexate and when initiated early. Etanercept is an attractive therapeutic option given the excellent safety profile, reduced immunogenicity and ease of administration. © 2013 Informa UK, Ltd.

Conaghan P.G.,University of Leeds | Conaghan P.G.,NIHR Leeds Musculoskeletal Biomedical Research Unit
Rheumatology International | Year: 2012

Non-steroidal anti-inflammatory drugs (NSAIDs) represent a diverse class of drugs and are among the most commonly used analgesics for arthritic pain worldwide, though long-term use is associated with a spectrum of adverse effects. The introduction of cyclooxygenase-2-selective NSAIDs early in the last decade offered an alternative to traditional NSAIDs with similar efficacy and improved gastrointestinal tolerability; however, emerging concerns about cardiovascular safety resulted in the withdrawal of two agents (rofecoxib and valdecoxib) in the mid-2000s and, subsequently, in an overall reduction in NSAID use. It is now understood that all NSAIDs are associated with some varying degree of gastrointestinal and cardiovascular risk. Guidelines still recommend their use, but little is known of how patients use these agents. While strategies and guidelines aimed at reducing NSAID-associated complications exist, there is a need for evidence-based algorithms combining cardiovascular and gastrointestinal factors that can be used to aid treatment decisions at an individual patient level. © Springer-Verlag 2011.

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