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Hand bone loss in early rheumatoid arthritis during a methotrexate-based treat-to-target strategy with or without adalimumab—a substudy of the optimized treatment algorithm in early RA (OPERA) trial

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Abstract

This study aims to investigate 1-year hand bone loss (HBL1-year) in early rheumatoid arthritis (RA) patients treated with a methotrexate (MTX) and intra-articular triamcinolone treat-to-target strategy +/− adalimumab and to determine if HBL6months is associated with radiographic progression after 2 years. In a clinical trial (OPERA) of 180 treatment-naive early RA patients, bone mineral density (BMD) was estimated from hand radiographs with digital X-ray radiogrammetry (DXR) at baseline, after 6 (n = 90) and 12 months (n = 70) of follow-up. Baseline and 2-year radiographs were scored according to the Sharp/van der Heijde method. Baseline characteristics and HBL6months (0–6 months changes in DXR-BMD) were investigated as predictors of structural damage by univariate linear (∆ total Sharp/van der Heijde score (TSS) as dependent variable) and logistic (+/−radiographic progression (∆TSS >0) as dependent variable) regression analyses. Variables with p < 0.10 were included in multivariable models. In 70 patients with available HBL1-year data, HBL1-year was median (interquartile range (IQR)) −1.9 (−3.3; −0.26 mg/cm2) in the MTX + placebo group and −1.8 (−3.6; 0.06) mg/cm2 in the MTX + adalimumab group, p = 0.98, Wilcoxon signed-rank. Increased HBL (compared to general population reference values) was found in 26/37 and 23/33 patients in the MTX + placebo and MTX + adalimumab groups, chi-squared = 0.99. In 90 patients with HBL6months data and 2-year radiographic data, HBL6months was independently associated with ∆TSS after 2 years (β = −0.086 (95% confidence interval = −0.15; −0.025) TSS unit/mg/cm2 increase, p = 0.006) but not with presence of radiographic progression (∆TSS >0) (OR 0.96 (0.92–1.0), p = 0.10). In early RA patients treated with a methotrexate-based treat-to-target strategy, the majority of patients had increased HBL1-year, irrespective of adalimumab; HBL6months was independently associated with ∆TSS after 2 years.

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Acknowledgements

The authors thank all participating patients, study nurses and laboratory technicians. Niels Steen Krogh (Zitelab Aps) is acknowledged for data management in the OPERA trial. The rheumatologists in the OPERA study group Ole Slot, Lars Kjær Nielsen, Henrik Skjødt, Ole Majgaard, Tove Lorenzen, Hans Christian Horn, Marcin Kowalski, Inger Lauge Johansen, Peter Mosborg Pedersen, Natalia Manilo and Henning Bliddal are acknowledged for their contribution to data collection.

Author information

Authors and Affiliations

  1. Copenhagen Center for Arthritis Research and the DANBIO registry, Center for Rheumatology and Spine Diseases, Rigshospitalet, Copenhagen, Denmark

    L. M. Ørnbjerg, M. Østergaard, S. B. Krintel, M. L. Hetland, Ole Slot & Henrik Skjødt

  2. Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    L. M. Ørnbjerg, M. Østergaard & M. L. Hetland

  3. Department of Endocrinology, Hvidovre Hospital, Copenhagen, Denmark

    T. Jensen

  4. King Christian X Hospital for Rheumatic Diseases, South Jutland Hospital, Gråsten, Denmark

    K. Hørslev-Petersen & J. Raun

  5. Institute of Regional Health Services Research, University of Southern Denmark, Odense, Denmark

    K. Hørslev-Petersen

  6. Department of Rheumatology, Institute of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark

    K. Stengaard-Pedersen, C. G. Ammitzbøll & A. Jørgensen

  7. Department of Rheumatology C, Odense University Hospital, Odense, Denmark

    P. Junker & H. Lindegaard

  8. Diagnostic Centre, Silkeborg Regional Hospital, Silkeborg, Denmark

    T. Ellingsen, M. Y. Dam & Tove Lorenzen

  9. Department of Medicine, Vejle Regional Hospital, Vejle, Denmark

    P. Ahlquist, T. Lottenburger & Hans Christian Horn

  10. Department of Rheumatology, Vendsyssel Hospital, Hjørring, Denmark

    A. Linauskas

  11. Department of Rheumatology, Aalborg University Hospital, Aalborg, Denmark

    A. Schlemmer

  12. Department of Rheumatology, Viborg Regional Hospital, Viborg, Denmark

    I. Hansen, Marcin Kowalski & Inger Lauge Johansen

  13. Department of Rheumatology, Odense University Hospital, Svendborg, Denmark

    Lars Kjær Nielsen

  14. Department of Rheumatology, Slagelse Hospital, Slagelse, Denmark

    Ole Majgaard

  15. Department of Rheumatology, Randers Regional Hospital, Randers, Denmark

    Peter Mosborg Pedersen

  16. Department of Rheumatology, Bispebjerg Hospital, Copenhagen, Denmark

    Natalia Manilo

  17. Department of Rheumatology, Parker Institute, Frederiksberg Hospital, Copenhagen, Denmark

    Henning Bliddal

Authors
  1. L. M. Ørnbjerg
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  2. M. Østergaard
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  3. T. Jensen
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  4. K. Hørslev-Petersen
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  5. K. Stengaard-Pedersen
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  6. P. Junker
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  7. T. Ellingsen
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  8. P. Ahlquist
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  9. H. Lindegaard
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  11. A. Schlemmer
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  12. M. Y. Dam
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  13. I. Hansen
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  14. T. Lottenburger
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  15. C. G. Ammitzbøll
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  16. A. Jørgensen
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  17. S. B. Krintel
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  18. J. Raun
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  19. M. L. Hetland
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  20. Ole Slot
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  21. Lars Kjær Nielsen
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  22. Henrik Skjødt
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  23. Ole Majgaard
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  24. Tove Lorenzen
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  25. Hans Christian Horn
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  26. Marcin Kowalski
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  27. Inger Lauge Johansen
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  28. Peter Mosborg Pedersen
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  29. Natalia Manilo
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  30. Henning Bliddal
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Consortia

OPERA Study Group

Corresponding author

Correspondence to L. M. Ørnbjerg.

Ethics declarations

The protocol was approved by the Regional ethics committee, Denmark (VEK-20070008), and carried out in accordance with good clinical practice. All procedures were performed in accordance with the Helsinki Declaration of 1975, as revised in 1983, and all patients signed an informed consent form.

Funding

Lykke Midtbøll Ørnbjergs work was financed by a clinical Ph. D. grant from the University of Copenhagen. For the OPERA trial, Abbott/AbbVie Denmark A/S provided adalimumab and placebo–adalimumab and an unrestricted grant for independent GCP monitoring, data management and statistical analysis. Meda Pharmaceuticals supplied triamcinolone hexacetonide. Sectra (Linköping, Sverige) performed the DXR analysis at a reduced cost. Abbott/AbbVie, Meda and Sectra were not involved in study setup, data collection, analysis or interpretation and had no influence on the publication of data.

Conflicts of interests

L.M. Ørnbjerg: None, M. Østergaard reports grants, personal fees and non-financial support from AbbVie, grants and personal fees from BMS, personal fees from Boehringer-Ingelheim, personal fees from Eli Lilly, personal fees and non-financial support from Janssen, grants, personal fees and non-financial support from Merck, personal fees and non-financial support from Pfizer, personal fees and non-financial support from Roche, grants, personal fees and non-financial support from UCB, personal fees from Celgene, personal fees from Sanofi, personal fees from Regeneron, personal fees from Novartis, outside the submitted work, T. Jensen: None, K. Hørslev-Petersen reports grants from AbbVie, Denmark, grants from Meda, Denmark, during the conduct of the study, K. Stengaard-Pedersen reports research grants from Roche, Media and Abbvie; speaking fees from UCB and Pfizer, outside of the submitted work, P. Junker: None, T. Ellingsen: None, P. Ahlquist: None, H. Lindegaard reports grants from Boehringer Ingelheim Danmark A/S, outside the submitted work, A. Linauskas: None, A. Schlemmer reports personal fees from MSD, Abbvie, Roche, research grants from Roche and Abbvie, outside of the submitted work, I. Hansen: None, M. Dam: None, T. Lottenburger: None, C.G. Ammitzbøll: None, A. Jørgensen: None, S.B. Krintell: None, J. Raun: None, M.L. Hetland: None.

Additional information

Lars Kjær Nielsen passed away in 2013.

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Ørnbjerg, L.M., Østergaard, M., Jensen, T. et al. Hand bone loss in early rheumatoid arthritis during a methotrexate-based treat-to-target strategy with or without adalimumab—a substudy of the optimized treatment algorithm in early RA (OPERA) trial. Clin Rheumatol 36, 781–789 (2017). https://doi.org/10.1007/s10067-016-3489-1

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  • DOI: https://doi.org/10.1007/s10067-016-3489-1

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