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Infliximab Biosimilar CT-P13 Observational Studies for Rheumatoid Arthritis, Inflammatory Bowel Diseases, and Ankylosing Spondylitis: Pooled Analysis of Long-Term Safety and Effectiveness

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Abstract

Introduction

Long-term, real-world safety and effectiveness data are required to support biosimilar use. This analysis pooled 5-year findings from observational studies of infliximab biosimilar CT-P13 treatment in patients with rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and ankylosing spondylitis (AS).

Methods

Patients enrolled in the CT-P13 4.2, 4.3, or 4.4 Korea/European Union registries were analysed if they had initiated infliximab treatment with CT-P13 (CT-P13 group) or had switched from reference infliximab to CT-P13 (switched to CT-P13 group). The primary objective was to investigate long-term safety by evaluating adverse events of special interest (AESIs) per the CT-P13 risk-management plan. Incidence rates per 100 patient-years (PYs) were calculated. Additional long-term safety endpoints, immunogenicity (assessments optional), and effectiveness were evaluated.

Results

Overall, 736 patients (642 CT-P13; 94 switched to CT-P13) were analysed. Median (range) exposure to CT-P13 was 19.433 (0.03–63.11) months overall. The incidence of treatment-emergent adverse events was 69.0% (CT-P13 group) and 60.6% (switched to CT-P13 group). Infusion-related reaction/hypersensitivity/anaphylactic reaction was the most frequent AESI overall, with an incidence of 4.3828 per 100 PY (95% confidence interval: 3.3603–5.6185). For most AESIs, incidence rates per 100 PY were broadly comparable between treatment groups, considering overlapping 95% confidence intervals. At baseline, 42/445 (9.4%) and 21/59 (35.6%) evaluable patients in the CT-P13 and switched to CT-P13 groups, respectively, were antidrug antibody (ADA)-positive. After CT-P13 treatment during the study, 188/425 (44.2%) evaluable patients had ≥ 1 ADA-positive result, including 147/425 (34.6%) patients with negative or no ADA results reported at baseline. Effectiveness tended to increase over time for all indications.

Conclusion

The analysis did not identify any new safety findings for patients with RA, IBD, and AS treated with CT-P13 for up to 5 years in those who were infliximab-naïve at CT-P13 initiation, or those who had switched from reference infliximab to CT-P13.

Trial Registration

ClinicalTrials.gov identifiers: NCT02557295 (CT-P13 4.2; retrospectively registered on 23 September 2015); NCT02326155 (CT-P13 4.3; retrospectively registered on 25 December 2014); NCT02557308 (CT-P13 4.4; retrospectively registered on 23 September 2015).

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References

  1. European Medicines Agency. Inflectra summary of product characteristics. 2020. https://www.ema.europa.eu/en/documents/product-information/inflectra-epar-product-information_en.pdf. Accessed 3 Jun 2021.

  2. European Medicines Agency. Remsima summary of product characteristics. 2021. https://www.ema.europa.eu/en/documents/product-information/remsima-epar-product-information_en.pdf. Accessed 3 Jun 2021.

  3. US Food and Drug Administration. Inflectra prescribing information. 2019. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/125544s009lbl.pdf. Accessed 3 Jun 2021.

  4. Ministry of Food and Drug Safety. Biological products: recombinant DNA products, Celltrion, Inc. https://www.mfds.go.kr/eng/brd/m_30/view.do?seq=69797. Accessed 3 Jun 2021.

  5. Generics and Biosimilars Initiative. Biosimilar monoclonal antibody approved in Korea. 2012. http://www.gabionline.net/Biosimilars/News/Biosimilar-monoclonal-antibody-approved-in-Korea. Accessed 3 Jun 2021.

  6. European Medicines Agency. Remicade summary of product characteristics. 2020. https://www.ema.europa.eu/en/documents/product-information/remicade-epar-product-information_en.pdf. Accessed 3 Jun 2021.

  7. US Food and Drug Administration. Remicade prescribing information. 2020. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/103772s5389s5391s5394lbl.pdf. Accessed 3 Jun 2021.

  8. Westhovens R, Wiland P, Zawadzki M, et al. Efficacy, pharmacokinetics and safety of subcutaneous versus intravenous CT-P13 in rheumatoid arthritis: a randomized phase I/III trial. Rheumatology (Oxford). 2021;60(5):2277–87.

    Article  Google Scholar 

  9. Park W, Hrycaj P, Jeka S, et al. A randomised, double-blind, multicentre, parallel-group, prospective study comparing the pharmacokinetics, safety, and efficacy of CT-P13 and innovator infliximab in patients with ankylosing spondylitis: the PLANETAS study. Ann Rheum Dis. 2013;72(10):1605–12.

    Article  CAS  Google Scholar 

  10. Yoo DH, Hrycaj P, Miranda P, et al. A randomised, double-blind, parallel-group study to demonstrate equivalence in efficacy and safety of CT-P13 compared with innovator infliximab when coadministered with methotrexate in patients with active rheumatoid arthritis: the PLANETRA study. Ann Rheum Dis. 2013;72(10):1613–20.

    Article  CAS  Google Scholar 

  11. Odgaard-Jensen J, Vist GE, Timmer A, et al. Randomisation to protect against selection bias in healthcare trials. Cochrane Database Syst Rev. 2011;2011(4):MR000012.

    PubMed Central  Google Scholar 

  12. Jones DS, Podolsky SH. The history and fate of the gold standard. Lancet. 2015;385(9977):1502–3.

    Article  Google Scholar 

  13. Golder S, Loke YK, Bland M. Meta-analyses of adverse effects data derived from randomised controlled trials as compared to observational studies: methodological overview. PLoS Med. 2011;8(5):e1001026.

    Article  Google Scholar 

  14. Ligthelm RJ, Borzi V, Gumprecht J, Kawamori R, Wenying Y, Valensi P. Importance of observational studies in clinical practice. Clin Ther. 2007;29 Spec No:1284–92.

    Article  Google Scholar 

  15. Lee SJ, Baek K, Lee S, Lee YJ, Park JE, Lee SG. Post-marketing pooled safety analysis for CT-P13 treatment of patients with immune-mediated inflammatory diseases in observational cohort studies. BioDrugs. 2020;34(4):513–28.

    Article  CAS  Google Scholar 

  16. Kay J, Schoels MM, Dörner T, et al. Consensus-based recommendations for the use of biosimilars to treat rheumatological diseases. Ann Rheum Dis. 2018;77(2):165–74.

    Article  CAS  Google Scholar 

  17. European Medicines Agency. Remsima public assessment report. 2019. https://www.ema.europa.eu/en/documents/assessment-report/remsima-epar-public-assessment-report_en.pdf. Accessed 3 Jun 2021.

  18. European Medicines Agency. Inflectra public assessment report. 2019. https://www.ema.europa.eu/en/documents/assessment-report/inflectra-epar-public-assessment-report_en.pdf. Accessed 3 Jun 2021.

  19. Goll GL, Jørgensen KK, Sexton J, et al. Long-term efficacy and safety of biosimilar infliximab (CT-P13) after switching from originator infliximab: open-label extension of the NOR-SWITCH trial. J Intern Med. 2019;285(6):653–69.

    Article  CAS  Google Scholar 

  20. Park W, Yoo DH, Miranda P, et al. Efficacy and safety of switching from reference infliximab to CT-P13 compared with maintenance of CT-P13 in ankylosing spondylitis: 102-week data from the PLANETAS extension study. Ann Rheum Dis. 2017;76(2):346–54.

    Article  CAS  Google Scholar 

  21. Yoo DH, Prodanovic N, Jaworski J, et al. Efficacy and safety of CT-P13 (biosimilar infliximab) in patients with rheumatoid arthritis: comparison between switching from reference infliximab to CT-P13 and continuing CT-P13 in the PLANETRA extension study. Ann Rheum Dis. 2017;76(2):355–63.

    Article  CAS  Google Scholar 

  22. Tanaka Y, Yamanaka H, Takeuchi T, et al. Safety and efficacy of CT-P13 in Japanese patients with rheumatoid arthritis in an extension phase or after switching from infliximab. Mod Rheumatol. 2017;27(2):237–45.

    Article  CAS  Google Scholar 

  23. Nakagawa T, Kobayashi T, Nishikawa K, et al. Infliximab biosimilar CT-P13 is interchangeable with its originator for patients with inflammatory bowel disease in real world practice. Intest Res. 2019;17(4):504–15.

    Article  Google Scholar 

  24. Fiorino G, Manetti N, Armuzzi A, et al. The PROSIT-BIO cohort: a prospective observational study of patients with inflammatory bowel disease treated with infliximab biosimilar. Inflamm Bowel Dis. 2017;23(2):233–43.

    Article  Google Scholar 

  25. Choquette D, Faraawi R, Chow A, Rodrigues J, Bensen WJ, Nantel F. Incidence and management of infusion reactions to infliximab in a prospective real-world community registry. J Rheumatol. 2015;42(7):1105.

    Article  CAS  Google Scholar 

  26. Thorne C, Bensen WG, Choquette D, et al. Effectiveness and safety of infliximab in rheumatoid arthritis: analysis from a Canadian multicenter prospective observational registry. Arthritis Care Res. 2014;66(8):1142–51.

    Article  CAS  Google Scholar 

  27. Kim TH, Lee SS, Park W, et al. A 5-year retrospective analysis of drug survival, safety, and effectiveness of the infliximab biosimilar CT-P13 in patients with rheumatoid arthritis and ankylosing spondylitis. Clin Drug Investig. 2020;40(6):541–53.

    Article  CAS  Google Scholar 

  28. Kim HA, Lee E, Lee SK, et al. Retention rate and long-term safety of biosimilar CT-P13 in patients with ankylosing spondylitis: data from the Korean College of Rheumatology Biologics registry. Clin Exp Rheumatol. 2020;38(2):267–74.

    PubMed  Google Scholar 

  29. Kim HA, Lee E, Lee SK, et al. Retention rate and safety of biosimilar CT-P13 in rheumatoid arthritis: data from the Korean College of Rheumatology Biologics registry. BioDrugs. 2020;34(1):89–98.

    Article  Google Scholar 

  30. Kurki P, van Aerts L, Wolff-Holz E, Giezen T, Skibeli V, Weise M. Interchangeability of biosimilars: a European perspective. BioDrugs. 2017;31(2):83–91.

    Article  CAS  Google Scholar 

  31. Gonczi L, Gecse KB, Vegh Z, et al. Long-term efficacy, safety, and immunogenicity of biosimilar infliximab after one year in a prospective nationwide cohort. Inflamm Bowel Dis. 2017;23(11):1908–15.

    Article  Google Scholar 

  32. Bálint A, Rutka M, Végh Z, et al. Frequency and characteristics of infusion reactions during biosimilar infliximab treatment in inflammatory bowel diseases: results from Central European nationwide cohort. Expert Opin Drug Saf. 2017;16(8):885–90.

    Article  Google Scholar 

  33. Gecse KB, Lovász BD, Farkas K, et al. Efficacy and safety of the biosimilar infliximab CT-P13 treatment in inflammatory bowel diseases: a prospective, multicentre, nationwide cohort. J Crohns Colitis. 2016;10(2):133–40.

    Article  Google Scholar 

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Acknowledgements

We thank all patients involved in the studies. Patients were not involved in the study design or dissemination of the results.

Funding

The studies reported in this article were funded by Celltrion, Inc. (Incheon, Republic of Korea). The journal’s Rapid Service Fee was also funded by Celltrion, Inc.

Medical Writing and Editorial Assistance

Medical writing support (including development of a draft outline and subsequent drafts in consultation with the authors, assembling tables and figures, collating author comments, copyediting, fact checking, and referencing) was provided by Beatrice Tyrrell, DPhil, at Aspire Scientific (Bollington, UK), and funded by Celltrion, Inc. (Incheon, Republic of Korea).

Authorship

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Authorship Contributions

Jae Hee Cheon, Seongsu Nah, Hyoun Woo Kang, Yun Jeong Lim, Sang-Hoon Lee, and Sung-Hwan Park contributed to patient enrolment and monitoring, and data collection and analysis. Sang Joon Lee, Sung Hyun Kim, Na Hyun Jung, Jeong Eun Park, Yeo Jin Lee, Da Bee Jeon, Yeon Mi Lee, and Jong Min Kim contributed to trial design and data analysis.

Prior Presentation

Pooled interim safety results from the studies reported in the present article have been published previously (Lee SJ, et al. BioDrugs. 2020;34:513–28). An e-poster reporting final results from the CT-P13 4.3 registry study will be presented virtually on 3 July 2021 at the 16th Congress of the European Crohn’s and Colitis Organisation (ECCO).

Disclosures

Jae Hee Cheon reports personal fees and non-financial support from Celltrion, Inc. during the conduct of the study and personal fees from AbbVie Korea, Ferring Korea, IQVIA, Janssen Korea, Shire Korea, and Takeda Korea outside the submitted work. Seongsu Nah reports non-financial support from Celltrion, Inc. during the conduct of the study. Sang Joon Lee and Sung Hyun Kim are employees of, and hold shares in, Celltrion, Inc. Na Hyun Jung, Jeong Eun Park, Yeo Jin Lee, Da Bee Jeon, Yeon Mi Lee, and Jong Min Kim are employees of Celltrion, Inc. Hyoun Woo Kang, Yun Jeong Lim, Sang-Hoon Lee and Sung-Hwan Park report no conflicts of interest. The current affiliation for Hyoun Woo Kang is the Division of Gastroenterology and Hepatology, Department of Internal Medicine, SMG-SNU Boramae Medical Center, Seoul, Republic of Korea.

Compliance with Ethics Guidelines

The studies were conducted in accordance with the Helsinki Declaration of 1964 and its later amendments, the International Conference on Harmonisation, and relevant region/country-specific regulations. Study protocols were approved by the relevant institutional/regional review boards/ethics committees (see Supplementary Methods, Table S1). All participants provided written, informed consent.

Data Availability

Most of the data generated or analysed during this study are included in this published article (and the accompanying Supplementary Material). Other datasets associated with the current study are not publicly available due to confidentiality but are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea

    Jae Hee Cheon

  2. Department of Internal Medicine, Soonchunhyuang University Hospital, Cheonan, Republic of Korea

    Seongsu Nah

  3. Department of Internal Medicine, Dongguk University Ilsan Hospital, Dongguk University, College of Medicine, Goyang, Republic of Korea

    Hyoun Woo Kang & Yun Jeong Lim

  4. Department of Rheumatology, College of Medicine, Kyung Hee University, Seoul, Republic of Korea

    Sang-Hoon Lee

  5. Arthritis and Rheumatism Center, Kyung Hee University Hospital at Gangdong, Seoul, Republic of Korea

    Sang-Hoon Lee

  6. Celltrion, Inc., Incheon, Republic of Korea

    Sang Joon Lee, Sung Hyun Kim, Na Hyun Jung, Jeong Eun Park, Yeo Jin Lee, Da Bee Jeon, Yeon Mi Lee & Jong Min Kim

  7. Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-Gu, Seoul, 137-701, Republic of Korea

    Sung-Hwan Park

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Correspondence to Sung-Hwan Park.

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Cheon, J.H., Nah, S., Kang, H.W. et al. Infliximab Biosimilar CT-P13 Observational Studies for Rheumatoid Arthritis, Inflammatory Bowel Diseases, and Ankylosing Spondylitis: Pooled Analysis of Long-Term Safety and Effectiveness. Adv Ther 38, 4366–4387 (2021). https://doi.org/10.1007/s12325-021-01834-3

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