Biosimilars in rheumatology: A review of the evidence and their place in the treatment algorithm

Abstract

Determining biosimilarity involves a comprehensive exercise with a focus on determining the comparability of the molecular characteristics and preclinical profile of the biosimilar and reference product, such that there is less need for extensive clinical testing to assure comparability of clinical outcomes. Three anti-TNF biosimilar agents are approved for patients with rheumatic diseases in the European Union. The infliximab (Remicade®) biosimilars CT-P13 (Remsima® and Inflectra®) and SB2 (Flixabi®) and the etanercept (Enbrel®) biosimilar SB4 (Benepali®) have shown close comparability to their reference medicinal products, having undergone extensive evaluations. Guidelines on the treatment of rheumatic diseases have acknowledged that biosimilars and biologic DMARDs (bDMARDs) are interchangeable in clinical practice, except when patients experience lack of efficacy or tolerability with the reference agent. Given that cost is a barrier to effective bDMARD use, the introduction of less costly biosimilars is likely to widen access and dissipate treatment inequalities. Physicians faced with prescribing decisions should be reassured by the robust and exhaustive process that is involved in assuring comparability of biosimilars with their reference agents. De novo usage of a biosimilar and switching to a biosimilar following lack of efficacy or tolerability with a different reference biologic agent are likely to be strategies most easily adopted, although switching during successful treatment should also be considered given the potential cost implications. The introduction of biosimilar bDMARDs has the potential to improve patient access to effective biologic therapy, to better accommodate restraints within healthcare budgets and to improve overall patient outcomes.

Keywords: CT-P13; SB2; SB4; biosimilar; rheumatic disease.

Fig. 1

Study design of key studies on biosimilars (A) CT-P13 PLANETRA study—RA. (B) CT-P13 PLANETAS study—AS. (C) SB2 phase III study—RA. (D) SB4 phase III study—RA and (E) GP2015 EGALITY study plaque-type psoriasis. Data taken from [19, 20, 22, 23, 25, 26, 35–37, 44–46, 51].

Fig. 2

Algorithm based on the 2016 EULAR recommendations on RA management ^a2010 ACR-EULAR classification criteria can support early diagnosis. ^bThe treatment target is clinical remission according to ACR-EULAR definition or, if remission is unlikely to be achievable, at least low disease activity; the target should be reached after 6 months, but therapy should be adapted or changed if no sufficient improvement is seen after 3 months. ^cMTX should be part of the first treatment strategy; while combination therapy of csDMARDs is not preferred by the Task Force, starting with MTX does not exclude its use in combination with other csDMARDs. ^dTNF inhibitors (adalimumab, certolizumab, etanercept, golimumab, infliximab, including EMA/FDA approved bsDMARDs), abatacept, IL-6 inhibitors or rituximab; in patients who cannot use csDMARDs as co-medication, IL-6 inhibitors and tsDMARDs have some advantages. ^eCurrent practice would be to start with a bDMARD (in combination with MTX or another csDMARD) because of the long-term experience compared with tsDMARDs (Jak inhibitors). ^fThe most frequently used combination comprises MTX, SSZ and HCQ. ^gDose reduction or interval increase can be safely done with all bDMARDs with little risk of flares; stopping is associated with high flare rates; most but not all patients can recapture their good state upon re-institution of the same bDMARD. ^hEfficacy and safety of bDMARDs after Jak inhibitor failure is unknown; also, efficacy and safety of an IL6-pathway inhibitor after another one has failed is currently unknown. ⁱEfficacy and safety of a Jak inhibitor after insufficient response to a previous Jak inhibitor is unknown. bDMARD: biologic DMARD; bsDMARD: biosimilar DMARD; csDMARD: conventional synthetic DMARD; EMA: European Medicines Agency; FDA, Food and Drug Administration; tsDMARD: targeted synthetic DMARD. Reproduced from EULAR recommendations for the management of RA with synthetic and biologic DMARDs: 2016 update, Smolen et al. ©2017 [6], with permission from BMJ Publishing Group Ltd.