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Comparative Efficacy and Safety of Biosimilar Rituximab and Originator Rituximab in Rheumatoid Arthritis and Non-Hodgkin’s Lymphoma: A Systematic Review and Meta-analysis

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Abstract

Background

Rituximab is a biologic medicine widely used for the treatment of autoimmune diseases and lymphoma. Several biosimilars of rituximab have been developed and marketed with the expiration of the originator rituximab’s patent; thus, systematic combination and analysis of the latest data on the efficacy and safety of biosimilars and the demonstration of the interchangeability of biosimilar agents are required.

Objective

The objective of this study was to collate available data from head-to-head randomized controlled trials (RCTs) and evaluate the efficacy and safety of biosimilar rituximab compared with the reference drug in patients with rheumatoid arthritis (RA) and non-Hodgkin’s lymphoma (NHL).

Methods

The PubMed, EMBASE, Cochrane Library, and Google Scholar databases were searched to identify head-to-head RCTs that directly compare the efficacy and safety of biosimilar rituximab and its originator. The efficacy outcome for RA was the American College of Rheumatology (ACR) response rates and the outcome for NHL was the response rate. The occurrence of adverse events (AEs) and anti-drug antibodies (ADAs) were evaluated for the safety outcome. Data on the pharmacokinetic profile were also included as a secondary outcome.

Results

Eleven head-to-head RCTs with 3163 patients were included (1744 patients with RA and 1419 patients with NHL). Biosimilars of rituximab showed similar efficacy in the clinical response in both RA and NHL. The pooled risk ratio (RR) of the ACR 20% response rate (ACR20) response in patients with RA at weeks 24 and 48 was 0.99 (p = 0.70, 95% confidence interval [CI] 0.92–1.06) and 1.04 (p = 0.73, 95% CI 0.83–1.31), respectively. The pooled RR of the overall response at week 24 in NHL patients was 1.02 (p = 0.31, 95% CI 0.98–1.07). No significant differences were found in the formation of ADAs (RR 0.86, p = 0.20, 95% CI 0.68–1.08) or AEs (RR 1.04, p = 0.30, 95% CI 0.97–1.12).

Conclusion

This systematic review and conventional meta-analysis demonstrated the overall similarity of the long-term efficacy and safety of biosimilar rituximab to those of originator rituximab in RA and NHL patients by combining direct evidence from head-to-head trials.

PROSPERO registration No. CRD42019125138.

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Acknowledgements

This research was supported by the Chung-Ang University Research Scholarship Grants, 2018 (Soohyun Lee) and by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2018R1D1A1B07046564).

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Authors and Affiliations

  1. Department of Health, Social and Clinical Pharmacy, College of Pharmacy, Chung-Ang University, 84, Heukseokro, Dongjak-gu, Seoul, 156-756, South Korea

    Soohyun Lee & EunYoung Kim

  2. College of Pharmacy, Gachon University, Inchon, South Korea

    Heeyoung Lee

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Contributions

SL and EK designed the study. SL and HL carried out data extraction and data analysis. SL wrote the initial manuscript. All the authors contributed to the revision of the article and approved the submission of the final manuscript.

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Correspondence to EunYoung Kim.

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Funding

This research is supported by the 2019 Chung-Ang University Research Scholarship Grants (Soohyun Lee) and by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2018R1D1A1B07046564).

Conflicts of interest

Soohyun Lee, Heeyoung Lee, and Eunyoung Kim declare that they have no competing interests related to this study.

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Ethical approval was not applicable for this systematic review and meta-analysis.

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Lee, S., Lee, H. & Kim, E. Comparative Efficacy and Safety of Biosimilar Rituximab and Originator Rituximab in Rheumatoid Arthritis and Non-Hodgkin’s Lymphoma: A Systematic Review and Meta-analysis. BioDrugs 33, 469–483 (2019). https://doi.org/10.1007/s40259-019-00376-z

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