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. 2016 Dec;30(6):525-570.
doi: 10.1007/s40259-016-0201-6.

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

Ira Jacobs  1 , Danielle Petersel  2 , Leah Isakov  2 , Sadiq Lula  3 , K Lea Sewell  2
Affiliations

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

Ira Jacobs et al. BioDrugs. 2016 Dec.

Abstract

Background: Clinicians are required to assimilate, critically evaluate, and extrapolate information to support appropriate use of biosimilars across indications.

Objectives: The 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.

Methods: MEDLINE®, 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.

Results: Proposed 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.

Conclusions: While 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.

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Conflict of interest statement

Compliance with Ethical Standards Author Contributions All authors were involved in drafting the article and revising it critically for important intellectual content. All authors read and approved the final manuscript submitted for publication. Conflict of interest IJ, DP and KLS are full-time employees and shareholders of Pfizer. LI was a full-time employee of Pfizer Inc. at the time the study was conducted. SL is a full-time employee of Envision Pharma Group, who were paid consultants to Pfizer in connection with the development of the SLR report that forms the basis of this manuscript. He was not compensated for his role in the development of this manuscript. Funding The SLR to support this manuscript was sponsored by Pfizer Inc.

Figures

Fig. 1
Fig. 1
Frequency of publications of reported named biosimilars in chronic inflammatory diseases. Note: publications were classified into the most relevant category, which in some cases was more than one. Therefore, the number of publications classified into each therapeutic area category does not sum to the total number of publications. For example, overlap in licensed indications for originators/biosimilars led to multiple categorization. Among the empirical references, several (seven) include both nonclinical and human data, and as such have been classified into both categories. IC Intended copy, RCT randomized controlled trial
Fig. 2
Fig. 2
Biosimilarity and a total treated patients for named biosimilars and intended copies in published clinical trials and b breadth of data for named biosimilars and intended copies in published analytical and nonclinical studies. ‘Degree of similarity’ for biosimilars and intended copies is inferred from the totality of evidence provided from all available published studies (up to 3 September 2015), and is based on the original conclusions made by the study investigators. The scale of reference used by each investigator was not accounted for, as it was not uniformly reported. * refers to agents that have already met the European Medicines Agency and/or US Food and Drug Administration requirements and have been approved as biosimilars. † based on different author interpretations of study data, intended copy Kikuzubam® purportedly exhibits some highly dissimilar and some identical physicochemical characteristics compared with the originator. ADA adalimumab, ETN etanercept, IC intended copy, INF infliximab, RTX rituximab
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References

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