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  • Efficacy and safety of the biosimilar ABP 501 compared with adalimumab in patients with moderate to severe rheumatoid arthritis: a randomised, double-blind, phase III equivalence study

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Clinical and epidemiological research
Extended report
Efficacy and safety of the biosimilar ABP 501 compared with adalimumab in patients with moderate to severe rheumatoid arthritis: a randomised, double-blind, phase III equivalence study
  1. Stanley Cohen1,
  2. Mark C Genovese2,
  3. Ernest Choy3,
  4. Fernando Perez-Ruiz4,
  5. Alan Matsumoto5,
  6. Karel Pavelka6,
  7. Jose L Pablos7,
  8. Warren Rizzo8,
  9. Pawel Hrycaj9,
  10. Nan Zhang10,
  11. William Shergy11,
  12. Primal Kaur10
  1. 1Metroplex Clinical Research Center, Dallas, Texas, USA
  2. 2Stanford University School of Medicine, Palo Alto, California, USA
  3. 3CREATE Centre, Section of Rheumatology, Institute of Infection and Immunity, Cardiff University, Cardiff, UK
  4. 4Rheumatology Division, Cruces University Hospital, OSI EE-Cruces and Biocruces Health Research Institute, Vizcaya, Spain
  5. 5Arthritis and Rheumatism Associates, Wheaton, Maryland, USA
  6. 6Na Slupi 4 Praha 2, Praha, Czech Republic
  7. 7Instituto de Investigación Hospital 12 de Octubre, Universidad Complutense de Madrid, Madrid, Spain
  8. 8Advanced Arthritis Care & Research, Scottsdale, Arizona, USA
  9. 9Department of Rheumatology and Clinical Immunology, Poznań University of Medical Sciences, Poznań, Poland
  10. 10Amgen Inc., Thousand Oaks, California, USA
  11. 11RANA Clinical Research Center, Huntsville, Alabama, USA
  1. Correspondence to Professor Stanley Cohen, Clinical Professor of Internal Medicine, University of Texas Southwestern Medical School, Medical Director, Metroplex Clinical Research Center Director, Rheumatology Division, Presbyterian Hospital, 8144 Walnut Hill Lane, Suite 800, Dallas, TX 75231, USA; Scohen{at}arthdocs.com

Abstract

Objectives ABP 501 is a Food and Drug Administration-approved biosimilar to adalimumab; structural, functional and pharmacokinetic evaluations have shown that the two are highly similar. We report results from a phase III study comparing efficacy, safety and immunogenicity between ABP 501 and adalimumab.

Methods In this randomised, double-blind, active comparator-controlled, 26-week equivalence study, patients with moderate to severe active rheumatoid arthritis (RA) despite methotrexate were randomised (1:1) to ABP 501 or adalimumab (40 mg) every 2 weeks. Primary endpoint was risk ratio (RR) of ACR20 between groups at week 24. Primary hypothesis that the treatments were equivalent would be confirmed if the 90% CI for RR of ACR20 at week 24 fell between 0.738 and 1.355, demonstrating that ABP 501 is similar to adalimumab. Secondary endpoints included Disease Activity Score 28-joint count-C reactive protein (DAS28-CRP). Safety was assessed via adverse events (AEs) and laboratory evaluations. Antidrug antibodies were assessed to determine immunogenicity.

Results A total of 526 patients were randomised (n=264, ABP 501; n=262 adalimumab) and 494 completed the study. ACR20 response at week 24 was 74.6% (ABP 501) and 72.4% (adalimumab). At week 24, the RR of ACR20 (90% CI) between groups was 1.039 (0.954, 1.133), confirming the primary hypothesis. Changes from baseline in DAS28-CRP, ACR50 and ACR70 were similar. There were no clinically meaningful differences in AEs and laboratory abnormalities. A total of 38.3% (ABP 501) and 38.2% (adalimumab) of patients tested positive for binding antidrug antibodies.

Conclusions Results from this study demonstrate that ABP 501 is similar to adalimumab in clinical efficacy, safety and immunogenicity in patients with moderate to severe RA.

Trial registration number NCT01970475; Results.

  • DMARDs (biologic)
  • rheumatoid arthritis
  • TNF-alpha
  • anti-TNF
  • inflammation

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

https://doi.org/10.1136/annrheumdis-2016-210459

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    Footnotes

    • Contributors Conception and design: PK and NZ. Analysis and interpretation of data: SC, MCG, EC, FP-R, AM, KP, JLP, WR, PH, NZ, WS and PK. Drafting the article and revising it critically for content: All authors. All authors reviewed and revised the manuscript and approved the final version to be published. All authors were involved in the decision to submit the manuscript for publication, and had the right to accept or reject comments or suggestions.

    • Funding Amgen Inc funded this study and participated in the design and conduct of the study; collection, management, analysis and interpretation of data; and preparation, review and approval of the manuscript.

    • Competing interests SC reports grants and personal fees from Amgen, during the conduct of the study; grants and personal fees from Abbvie, Boehringer Ingelheim, Pfizer and Sandoz, outside the submitted work. MCG reports grants and personal fees from Amgen, AbbVie and Pfizer, and personal fees from Sandoz, FKb, Samsung BioEpis, Merck, Celltrion and Boehringer, during the conduct of the study. EC reports grants and personal fees from Amgen, during the conduct of the study; personal fees from Boehringer Ingelheim, Chelsea Therapeutics, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Hospita, ISIS, Jazz Pharmaceuticals, Janssen, MedImmune, Merrimack Pharmaceutical, Merck, Napp, Novartis, Regeneron, Sanofi-Aventis, Schering Plough, Synovate and Tonix and grants and personal fees from Chugai Pharma, Ferring Pharmaceuticals, Novimmune, Pfizer, Pierre Fabre, Roche and UCB, outside the submitted work. FP-R reports grants from Amgen, during the conduct of the study; and personal fees from Amgen, outside the submitted work. AM reports grants and personal fees from Amgen, during the conduct of the study; grants and personal fees from AbbVie, Pfizer and Bristol-Myers Squibb, grants from Takeda, Janssen, Gilead and UCB and personal fees from GlaxoSmithKline, outside the submitted work. JLP reports lecturing and consultancy fees from Roche, Novartis, Pfizer and Lilly, outside the submitted work. NZ and PK are employees of Amgen Inc.

    • Patient consent Written informed consent was obtained from each patient prior to study enrolment.

    • Ethics approval This study was conducted in accordance with the current International Conference on Harmonization good clinical practice guidelines and the Declaration of Helsinki. The study protocol was approved by the institutional review board or independent ethics committee at each participating site and adhered to all local regulatory requirements including data protection requirements.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data sharing statement All data from this study, published and unpublished, were made available to all authors. Further inquiry regarding availability of the data can be addressed to PK of Amgen, Inc.

    • Correction notice This paper has been amended since it was published Online First. Owing to a scripting error, some of the publisher names in the references were replaced with ’BMJ Publishing Group'. This only affected the full text version, not the PDF. We have since corrected these errors and the correct publishers have been inserted into the references.