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Comparative effectiveness of two adalimumab biosimilars in 1318 real-world patients with inflammatory rheumatic disease mandated to switch from originator adalimumab: nationwide observational study emulating a randomised clinical trial
  1. Hafsah Nabi1,2,
  2. Stylianos Georgiadis1,
  3. Anne Gitte Loft3,4,
  4. Oliver Hendricks5,6,
  5. Dorte Vendelbo Jensen7,8,
  6. Marlene Andersen9,
  7. Stavros Chrysidis10,
  8. Ada Colic11,
  9. Kamilla Danebod12,
  10. Mohamad Redha Hussein13,
  11. Maren Høgberget Kalisz8,
  12. Salome Kristensen14,
  13. Niels Lomborg15,
  14. Natalia Manilo16,
  15. Heidi Lausten Munk17,
  16. Jens Kristian Pedersen18,
  17. Johnny Lillelund Raun19,
  18. Frank Mehnert20,
  19. Niels Steen Krogh21,
  20. Merete Lund Hetland1,2,
  21. Bente Glintborg1,2
  1. 1DANBIO and Copenhagen Center for Arthritis Research (COPECARE), Center for Rheumatology and Spine Diseases, Centre of Head and Orthopedics, Rigshospitalet, Copenhagen, Denmark
  2. 2Department of Clinical Medicine, University of Copenhagen Faculty of Health and Medical Sciences, Copenhagen, Denmark
  3. 3Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark
  4. 4Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
  5. 5Danish Hospital for Rheumatic Diseases, University Hospital of Southern Denmark, Sønderborg, Denmark
  6. 6Department of Regional Health Research, University of Southern Denmark, Odense, Denmark
  7. 7Department of Internal Medicine, Rønne Hospital, Rønne, Denmark
  8. 8Department of Rheumatology, Gentofte and Herlev Hospital, Copenhagen University Hospital, Gentofte, Denmark
  9. 9Department of Rheumatology, North Denmark Regional Hospital, Hjørring, Denmark
  10. 10Department of Rheumatology, Esbjerg Hospital, Esbjerg, Denmark
  11. 11Department of Rheumatology, Zealand University Hospital, Køge, Denmark
  12. 12Department of Rheumatology, Center for Rheumatology and Spine Diseases, Centre of Head and Orthopedics, Rigshospitalet, Copenhagen University Hospital, Glostrup, Denmark
  13. 13Department of Rheumatology, Slagelse Hospital, Slagelse, Denmark
  14. 14Department of Rheumatology, Aalborg University Hospital, Aalborg, Denmark
  15. 15Department of Rheumatology, Vejle Hospital Lillebælt, Vejle, Denmark
  16. 16Department of Rheumatology, Frederiksberg Hospital, Copenhagen, Denmark
  17. 17Department of Rheumatology, Odense University Hospital, Odense C, Denmark
  18. 18Rheumatology Section, Department of Medicine M, Svendborg Hospital, Svendborg, Denmark
  19. 19Department of Rheumatology, Hospital Lillebælt, Fredericia, Kolding, Denmark
  20. 20Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark
  21. 21Zitelab Aps, Copenhagen, Denmark
  1. Correspondence to Dr Hafsah Nabi, DANBIO and Copenhagen Center for Arthritis Research (COPECARE), Center for Rheumatology and Spine Diseases, Centre of Head and Orthopedics, Rigshospitalet, Copenhagen, Denmark; hafsah.nabi{at}regionh.dk

Abstract

Objectives In 2018, a nationwide mandatory switch from originator to biosimilar adalimumab was conducted in Denmark. The available biosimilar was GP2017 (Hyrimoz) in Eastern regions and SB5 (Imraldi) in Western regions. We aimed to assess the comparative effectiveness of GP2017 versus SB5 in patients with rheumatoid arthritis (RA)/psoriatic arthritis (PsA)/axial spondyloarthritis (AxSpA).

Methods Observational cohort study based on the DANBIO registry with geographical cluster pseudo-randomisation, analysed by emulating a randomised clinical trial. Main outcome was adjusted 1-year treatment retention (Cox regression). Furthermore, 6 months’ remission rates (logistic regression), reasons for withdrawal and back-switching to originator were investigated (overall and stratified by indication).

Results Overall, of 1570 eligible patients, 1318 switched and were included (467 RA/321 PsA/530 AxSpA); 623 (47%) switched to GP2017, 695 (53%) to SB5. Baseline characteristics of the two clusters were largely similar, but some differences in registration practice were observed. The combined 1-year retention rate for the two biosimilars was 89.5%. Compared with SB5, estimated risk of withdrawal for GP2017 was lower (HR 0.60; 95% CI 0.42 to 0.86) and 6 months’ remission rate was higher (OR 1.72; 95% CI 1.25 to 2.37). Stratified analyses gave similar results (statistically significant for RA). During 1 year, 8.5% and 12.9% withdrew GP2017 and SB5, respectively (primarily lack of effect and adverse events), of whom 48 patients (3.6%) back-switched.

Conclusion This head-to-head comparison of GP2017 versus SB5 following a mandatory switch from the originator indicated differences in effectiveness in routine care. This may reflect a true difference, but other explanations, for example, differences in excipients, differences between clusters and residual confounding cannot be ruled out.

  • biosimilar pharmaceuticals
  • adalimumab
  • epidemiology

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

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Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

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Footnotes

  • Handling editor Josef S Smolen

  • MLH and BG shared last authorship and contributed equally to the paper.

  • Correction notice This article has been corrected since it published Online First. The author, Dorte Vendelbo Jensen, has been added.

  • Contributors Study conception and design: HN, SG, BG and MLH. Acquisition of data: HN, SG, BG, MLH, FM and NSK. Statistical analysis: HN, SG, BG and MLH. All authors contributed to the interpretation of the data. HN, SG, BG and MLH wrote the manuscript. All authors critically revised the manuscript. All authors revised and approved the final manuscript to be published.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests AGL: AbbVie, Eli Lilly Denmark A/S, Janssen-Cilag A/S, MSD, Novartis, Pfizer, UCB teaching or consultancy fees. OH: AbbVie, Pfizer, Novartis. MLH: AbbVie, Biogen, BMS, Celtrion, Eli Lilly Denmark A/S, Janssen Biologics BV, Lundbeck Fonden, MSD, Pfizer, Roche, Samsung Bioepis, Sandoz. Furthermore, chair of the steering committee of the Danish Rheumatology Quality Registry (DANBIO), which receives public funding from the hospital owners and funding from pharmaceutical companies. Co-chair EuroSpA, which generates real-world evidence of treatment of psoriatic arthritis and axial spondyloarthritis based on secondary data and is partly funded by Novartis. BG: BMS, Pfizer, Sandoz (research grants).

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

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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