Reviewing the evidence for biosimilars: key insights, lessons learned and future horizons

Abstract

Biologic therapies have become central to the long-term management of many chronic diseases, including inflammatory rheumatic diseases. Over recent years, the development and licensing pathways for biosimilars have become more standardized, and several biosimilars have been made available for patients with inflammatory rheumatic diseases, such as RA. Pre-licensing requirements for biosimilars mandate the demonstration of comparability with reference products in terms of clinical activity, safety and immunogenicity, whereas post-marketing surveillance and risk minimization requirements are set in place to ensure that long-term, real-world safety data are collected to assess biosimilars in clinical practice. These measures should provide a foundation for physician confidence in biosimilars, which can be established further through clinical experience. Biosimilars may help to fill an unmet need by improving patient access to effective biologic treatments for chronic diseases. Greater access may result in additional clinical benefits, with appropriate use of biologic therapies according to treatment guidelines being associated with improved outcomes and the potential for reduced costs of care. Key challenges for the integration of biosimilars into everyday practice include questions about interchangeability, switching and automatic substitution. Several switching studies have shown that biosimilars can be used in place of reference products while maintaining efficacy and safety. Additional ongoing studies and registries may help to optimize the process of switching, and different funding models are examining the optimal mechanisms to ensure effective uptake of these new treatments.

Keywords: biologics; immunogenicity; interchangeability; rheumatologic biosimilars; risk minimization; switching.

Fig. 1

Number of manufacturing changes for monoclonal antibodies in their European Public Assessment Reports according to risk category Reproduced from: Vezér B, Buzás Z, Sebeszta M, Zrubka Z. Authorized manufacturing changes for therapeutic monoclonal antibodies (mAbs) in European Public Assessment Report (EPAR) documents. Curr Med Res Opin 2016;32:829–34 [59]. Reprinted by permission of the publisher (Taylor & Francis).

Fig. 2

Approval and reimbursement of biologic DMARDs in Europe The mean number of bDMARDs approved and reimbursed varied across the 46 European countries in this study, with a different profile being observed for EU member states compared with non-EU member states. Data taken from [3]. bDMARDs: biologic DMARDs; EU: European Union.

Fig. 3

Access to biologic DMARDs according to gross domestic product per capita Analysis based on GDP in dollars in 44 countries. The size of the bubbles is proportional to the population size of the country. Reproduced from: Putrik P, Ramiro S, Kvien TK et al. Inequalities in access to biological and synthetic DMARDs across 46 European Countries. Ann Rheum Dis 2014;73:198–206, © 2014 [3]. With permission from BMJ Publishing Group Ltd. AL: Albania; AM: Armenia; AT: Austria; BA: Bosnia and Herzegovina; bDMARD: biologic DMARD; BE: Belgium; BG: Bulgaria; BY: Belarus; CH: Switzerland; CY: Cyprus; CZ: Czech Republic; DE: Germany; DK: Denmark; EE: Estonia; ES: Spain; FI: Finland; FR: France; GDP: gross domestic product; GE: Georgia; GR: Greece; HR: Croatia; HU: Hungary; IE: Ireland; IS: Iceland; IT: Italy; KZ: Kazakhstan; LT: Lithuania; LU: Luxembourg; LV: Latvia; MD: Moldova; ME: Montenegro; MK: Macedonia; MT: Malta; NL: The Netherlands; NO: Norway; PL: Poland; PT: Portugal; RO: Romania; RS: Serbia; RU: Russia; SE: Sweden; SK: Slovakia; SL: Slovenia; TR: Turkey; UA: Ukraine; UK: United Kingdom.