Biosimilars in the treatment of rheumatoid arthritis: a pharmacokinetic overview

ABSTRACTIntroduction As of May 2023, 19 and 18 biosimilars have been approved for the treatment of rheumatoid arthritis (RA) by the European Medicines Agency (EMA) and United States Food and Drug Administration (US FDA) respectively.Area covered Pharmacokinetic results of phase 1 studies of approved biosimilars were reviewed by systematic literature search. The impact of immunogenicity on the pharmacokinetic data and clinical response was assessed, and the potential benefit of monitoring serum concentrations of biologic drugs is discussed. The advantage of subcutaneous CT-P13 (an infliximab biosimilar) in clinical practice is reviewed.Expert opinion Biosimilars are approved based on the totality of evidence including comparable physiochemical properties, PK / PD profiles, and clinical efficacy and safety to the originator. To utilize biosimilars more effectively, physicians should be aware of the utility of combination DMARD therapy to reduce immunogenicity and maintain efficacy and PK profile. PK monitoring, however, is not currently recommended in clinical practice. CT-P13 subcutaneous (SC) is the first SC infliximab used for treatment of RA patients. Based on data from clinical studies and the real world, SC-infliximab is an attractive therapeutic option compared to IV formulations of infliximab based on its efficacy, pharmacokinetics, patient-reported outcomes, and safety profile.KEYWORDS: Biosimilarrheumatoid arthritispharmacokineticsimmunogenicitymonitoringsubcutaneousCT-P13bio-better Article highlights As of May 2023, 19 and 18 biosimilars have been approved by the EMA and US FDA respectively for the treatment of RA.Anti-TNF and RTX biosimilars are effective for RA treatment options as their originators.Switching from an originator biologic to single or multiple biosimilars does not have detrimental effect on PK, immunogenicity, clinical efficacy, or safety.Immunogenicity is an inevitable phenomenon linked to treatment with a biologic agent, especially monoclonal antibodies compared to fusion proteins alike etanercept and abatacept.Anti-drug antibodies (ADAb) are associated with lower drug concentrations and linked to weaker clinical response to biologic agent. Healthcare specialists should focus on combination DMARD therapies such as methotrexate to maintain efficacy and PK profile while reducing immunogenicity.PK monitoring aligned with ADAb measurement may be beneficial for patients with an inadequate clinical response or high possibility of adverse events, but current EULAR guideline does not recommend this personalized approach.CT-P13 SC was the first SC IFX formulation used to treat patients with RA. Based on data from clinical studies and the real world, SC-infliximab is an attractive therapeutic option compared to IV formulations of infliximab in terms of improved efficacy, higher pre-dose drug concentrations, better patient reported outcomes and similar safety.Technical advances, have facilitated the development of bio-betters or value-added biosimilars. To date, regulatory processes and pathways differ between the EMA and US FDA. However, improved versions of biosimilars may provide a new paradigm for the treatment of RA through improved efficacy, safety and PK profile and reduced immunogenicity.Declaration of interestDH Yoo is an outside director of Celltrion, Co. Ltd. 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.Reviewer disclosuresPeer reviewers on this manuscript have no relevant financial or other relationships to disclose.Additional informationFundingThis paper was not funded.