Biosimilars for the Treatment of Chronic Inflammatory Diseases: A Systematic Review of Published Evidence

Abstract

BackgroundClinicians are required to assimilate, critically evaluate, and extrapolate information to support appropriate use of biosimilars across indications.ObjectivesThe objective of this study was to systematically collate all published data in order to assess the weight (quantity and quality) of available evidence for each molecule and inform and support healthcare decision-making in chronic inflammatory diseases.MethodsMEDLINE®, EMBASE®, and ISI Web of Science® were searched to September 2015. Selected conference proceedings were searched from 2012 to July 2015. Studies disclosing biosimilars with unique identifiers were categorized by originator, study type, and indication. Risk of bias assessments were performed. Intended copies were differentiated as commercially available agents without evidence of rigorous comparative biosimilarity evaluations.ResultsProposed biosimilars for adalimumab, etanercept, infliximab, and rituximab are reported in the published literature. Across indications, approved biosimilars infliximab CT-P13, SB2, and etanercept SB4 have published studies involving the largest number of patients or healthy subjects (n = 1405, 743, and 734, respectively), mostly in rheumatoid arthritis. At data cut-off, only CT-P13 had published data in ankylosing spondylitis (n = 250; randomized control trial) and ulcerative colitis/Crohn’s disease (n = 336; observational studies). Published data were not available for ongoing studies in psoriasis patients. Four intended copies were identified in published studies (total: n = 1430; n = 1372 in observational studies). Thematic analysis of non-empirical publications showed that indication extrapolation remains an issue, particularly for gastroenterologists.ConclusionsWhile most agents display a moderate to high degree of similarity to their originator in the published studies identified, large discrepancies persist in the overall amount and type of data available in the public domain. Significant gaps exist particularly for intended copies, reinforcing the need to maintain a clear differentiation between these molecules and true biosimilars.Electronic supplementary materialThe online version of this article (doi:10.1007/s40259-016-0201-6) contains supplementary material, which is available to authorized users.

2017 recommendations of the Brazilian Society of Rheumatology for the pharmacological treatment of rheumatoid arthritis

“…bsDMARDs have been shown to be safe and effective when used as an alternative to boDMARDs (moderate evidence). There were no differences in ACR20 and ACR70 response rates, disease activity (moderate evidence), or severe adverse events of the bsDMARDs adalimumab, etanercept, infliximab, and rituximab compared with their respective boDMARDs [134][135][136][137][138][139][140]. The development of anti-drug antibodies was similar between bsDMARDs and boDMARDs (moderate evidence), and lower for the bsDMARD of etanercept compared with the boDMARD (high evidence) [134].…”

Global Acceptance of Biosimilars: Importance of Regulatory Consistency, Education, and Trust

“… Monoclonal antibody and fusion protein biosimilar development pipeline. Based on named potential or approved biosimilars identified in the systematic literature review by Jacobs et al . Note that noncomparable biotherapeutic products (i.e., products intended to “copy” an already licensed product that are authorized without a complete exercise of head‐to‐head comparison with the originator) are not included, and the cutoff date for the literature review was September 2015.…”

“…Several biosimilar regulatory guidelines specify that the reference product used during the comparison exercise should be licensed in that country or region [10, 11, 26, 28]. The first [35][36][37]. Note that noncomparable biotherapeutic products (i.e., products intended to "copy" an already licensed product that are authorized without a complete exercise of head-to-head comparison with the originator) are not included, and the cutoff date for the literature review was September 2015. biosimilar guideline from the EMA, for example, stated "the chosen reference medicinal product, defined on the basis of its marketing authorisation in the [European] Community, should be used throughout the comparability program for quality, safety and efficacy studies" [24].…”

Uptake of rheumatology biosimilars in the absence of forced switching

“…For regulatory approval, pharmacokinetics, pharmacodynamics and efficacy should be demonstrated to be comparable to the originator drug. [2] Because of the complex structure of bDMARDs, and the non-identical manufacturing processes for originator products and biosimilars, the market entry of biosimilars has been linked to concerns from patients and from their care-providers regarding their use in clinical practice. In particular, there is limited data on whether switching from an originator product to its biosimilar (the originator has reached its intended effect and the medical condition does not warrant replacement to a biosimilar, henceforth referred to as non-medical switch) can be made without loss of effectiveness or increased risk of adverse events.…”