Immunogenicity of anti-TNF biologic agents in the treatment of rheumatoid arthritis

ABSTRACT

Introduction: The use of biologic disease-modifying anti-rheumatic drugs (DMARDs), including therapeutic antibodies, antibody fragments and protein constructs that target key mediators in the pathophysiology of rheumatoid arthritis (RA), has improved the chance of achieving low disease activity and clinical remission. However, individual patients respond differently to biologic DMARD therapy, particularly the tumor necrosis factor (TNF) inhibitors.

Areas covered: While the variation of clinical response may be related to pharmacogenetic and other unknown factors, immunogenicity associated with some of these agents may contribute in part to a lack of efficacy and immune-mediated side effects. Timely detection of immunogenicity may avoid continued administration of ineffective treatment, and reduce unnecessary risks and costs. Access to and appropriate implementation of clinically validated drug level assays is required.

Expert opinion: There are currently no evidence-based recommendations to guide biologic therapy on the basis of drug level and immunogenicity testing but as more data become available and better tests are developed, a strategy of immunopharmacologic guidance to individualize treatment of RA will emerge. The potential benefits of this approach must be balanced against the costs of monitoring, and further research is required.

KEYWORDS:

• Antidrug antibodies
• anti-TNF therapies
• immunogenicity
• rheumatoid arthritis

Article highlights

• Individual RA patients respond differently to biologic DMARD therapy, particularly the TNF inhibitors. Lack or loss of efficacy and immune-mediated side effects may be partly attributable to the immunogenicity associated with some of these agents.

• Timely detection of immunogenicity may avoid continued administration of ineffective treatment, and reduce unnecessary risks and costs.

• There are currently no evidence-based recommendations to guide biologic therapy on the basis of drug level and immunogenicity testing, but an immunopharmacologic approach to individualizing treatment is likely to emerge in the future.

• The potential benefits of this approach need to be balanced against the costs of monitoring.

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Financial and competing interests disclosure

Medical writing support was provided by Susanne Gilbert at ACUMED, an Ashfield Company, and was funded by Pfizer Inc. WC Tsai has received consultation fees from Abbvie, Chugai, Eisai, Janssen, Novartis and Pfizer. JCC Wei has received research grants or consultation fees from Abbvie, Bristol-Myers Squibb, Celgene, Chugai, Eisai, Janssen, Novartis, Pfizer, Sanofi-Aventis, TSH Taiwan and UCB Pharma. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.