Role of Biosimilars in the Treatment of Rheumatic Diseases
Role of Biosimilars in the Treatment of Rheumatic Diseases
The first biological therapeutics in rheumatology are approaching patent expiration, encouraging development of 'follow-on' versions, known as 'biosimilars'. Biological agents range from simple replacement hormones to complex monoclonal antibodies and soluble receptors: large, intricate proteins with unique tertiary and quaternary structures that are inherently difficult to replicate. Post-translational modifications, such as glycosylation, may occur from changes in cell lines and/or manufacturing processes, resulting in products that are highly similar, but not identical, to approved 'reference' agents, hence, the term 'biosimilar', rather than 'bioidentical'. Even minor modifications in manufacturing processes, which iteratively occur with reference products due to improvements in efficiency, scale up to meet commercial demands or changes in manufacturing sites, may alter biological function and/or immunogenicity, potentially changing their safety and efficacy profile. As biosimilars are now in randomised controlled trials for treatment of rheumatic diseases, rheumatologists face decisions regarding equipoise and will need to consider their clinical use versus reference products. A clear understanding of the inherent differences between reference antibodies and biosimilars, their clinical implications and the processes governing regulation, approval and clinical use of biosimilars, is paramount. A panel of international experts in the field of rheumatology recently convened to evaluate and discuss these issues.
The introduction of biological therapeutics for treatment of rheumatic diseases has significantly improved patient outcomes. With some of these 'reference (originator) products' approaching patent expiration, manufacturers are developing follow-on versions. Biosimilars may improve access to expensive biological agents; however, concerns have been raised regarding their clinical use. In particular, due to the complexities of manufacturing 'copies' of biological therapeutics, physicians have questioned whether biosimilars will confer identical biological function, efficacy and toxicity to reference products, both in the short and long term. These concerns are not without substantiation, since even minor modifications in manufacturing processes, which iteratively occur with reference products, may alter biological functions and/or immunogenicity, potentially changing their safety and efficacy profile ( Table 1 ). Biological agents range from simple replacement hormones to complex monoclonal antibodies (mAbs) and soluble receptor constructs (Cepts)—large, intricate proteins with unique tertiary and quaternary structures that are inherently difficult to replicate. Post-translational modifications, such as glycosylation, may occur from changes in cell lines and/or manufacturing processes, resulting in products that are highly similar, but not identical to approved 'reference' agents, hence the term 'biosimilar', rather than 'bioidentical'. The potential for protein modification to alter biological function is especially true for intricate therapeutic proteins, such as mAbs and Cepts.
With the expected introduction of biosimilar mAbs and Cepts, it is important that rheumatologists are familiar with biosimilars, so allowing informed treatment decisions. In order to facilitate this, a panel of international experts convened in Berlin in April 2012 for the roundtable on 'the role of biosimilars in the treatment of rheumatic diseases'. The roundtable provided a forum at which to discuss the potential clinical utility of biosimilars in rheumatology, implications for product efficacy and safety, and their impact on patient care. This article reviews the topics discussed at this meeting, providing physicians with current information in this rapidly evolving field.
Abstract and Introduction
Abstract
The first biological therapeutics in rheumatology are approaching patent expiration, encouraging development of 'follow-on' versions, known as 'biosimilars'. Biological agents range from simple replacement hormones to complex monoclonal antibodies and soluble receptors: large, intricate proteins with unique tertiary and quaternary structures that are inherently difficult to replicate. Post-translational modifications, such as glycosylation, may occur from changes in cell lines and/or manufacturing processes, resulting in products that are highly similar, but not identical, to approved 'reference' agents, hence, the term 'biosimilar', rather than 'bioidentical'. Even minor modifications in manufacturing processes, which iteratively occur with reference products due to improvements in efficiency, scale up to meet commercial demands or changes in manufacturing sites, may alter biological function and/or immunogenicity, potentially changing their safety and efficacy profile. As biosimilars are now in randomised controlled trials for treatment of rheumatic diseases, rheumatologists face decisions regarding equipoise and will need to consider their clinical use versus reference products. A clear understanding of the inherent differences between reference antibodies and biosimilars, their clinical implications and the processes governing regulation, approval and clinical use of biosimilars, is paramount. A panel of international experts in the field of rheumatology recently convened to evaluate and discuss these issues.
Introduction
The introduction of biological therapeutics for treatment of rheumatic diseases has significantly improved patient outcomes. With some of these 'reference (originator) products' approaching patent expiration, manufacturers are developing follow-on versions. Biosimilars may improve access to expensive biological agents; however, concerns have been raised regarding their clinical use. In particular, due to the complexities of manufacturing 'copies' of biological therapeutics, physicians have questioned whether biosimilars will confer identical biological function, efficacy and toxicity to reference products, both in the short and long term. These concerns are not without substantiation, since even minor modifications in manufacturing processes, which iteratively occur with reference products, may alter biological functions and/or immunogenicity, potentially changing their safety and efficacy profile ( Table 1 ). Biological agents range from simple replacement hormones to complex monoclonal antibodies (mAbs) and soluble receptor constructs (Cepts)—large, intricate proteins with unique tertiary and quaternary structures that are inherently difficult to replicate. Post-translational modifications, such as glycosylation, may occur from changes in cell lines and/or manufacturing processes, resulting in products that are highly similar, but not identical to approved 'reference' agents, hence the term 'biosimilar', rather than 'bioidentical'. The potential for protein modification to alter biological function is especially true for intricate therapeutic proteins, such as mAbs and Cepts.
With the expected introduction of biosimilar mAbs and Cepts, it is important that rheumatologists are familiar with biosimilars, so allowing informed treatment decisions. In order to facilitate this, a panel of international experts convened in Berlin in April 2012 for the roundtable on 'the role of biosimilars in the treatment of rheumatic diseases'. The roundtable provided a forum at which to discuss the potential clinical utility of biosimilars in rheumatology, implications for product efficacy and safety, and their impact on patient care. This article reviews the topics discussed at this meeting, providing physicians with current information in this rapidly evolving field.
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