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Similar lipid level changes in early rheumatoid arthritis patients following 1-year treat-to-target strategy with adalimumab plus methotrexate versus placebo plus methotrexate: secondary analyses from the randomised controlled OPERA trial

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Abstract

To compare changes in low-density lipoprotein cholesterol and other lipids in patients with rheumatoid arthritis (RA) randomised to a 1-year treat-to-target strategy with either adalimumab plus methotrexate or placebo plus methotrexate. Prespecified secondary analyses from the OPERA trial, where 180 early and treatment-naïve RA patients received methotrexate 20 mg once weekly in combination with either placebo or subcutaneous adalimumab 40 mg every other week. Serum lipid levels were measured at baseline and after 1 year. Changes in lipid levels were analysed using mixed linear models based on the intention-to-treat (ITT) population. Overall, 174 patients were included in the ITT population (adalimumab plus methotrexate n = 86; placebo plus methotrexate n = 88). Differences between changes in lipid levels were low-density lipoprotein cholesterol 0.18 mmol/l [95% CI − 0.05 to 0.42], total cholesterol 0.27 mmol/l [− 0.002 to 0.54], high-density lipoprotein cholesterol 0.05 mmol/l [− 0.06 to 0.15], triglycerides 0.11 mmol/l [− 0.08 to 0.29], very-low-density lipoprotein cholesterol 0.03 mmol/l [− 0.05 to 0.12], and non-high-density lipoprotein cholesterol 0.22 mmol/l [− 0.02 to 0.46]. In early RA patients treated to tight control of inflammation over a period of 1 year with either adalimumab plus methotrexate or placebo plus methotrexate, changes in lipid levels were similar. Trial registration number: NCT00660647.

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Fig. 1

Availability of data and material

Use of data to other purposes must be applied to OPERA steering committee, the Danish Data Protection Agency and the Ethics Committee of the Central Denmark Region.

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Acknowledgements

We thank the patients who participated in the OPERA trial. Results have been presented as a poster at EULAR 2020.

Funding

This work was supported by grants from The Danish Rheumatism Association [R142-A4110 and R135-A3684 to DM], Region of Southern Denmark [to DM], and University of Southern Denmark [to DM].

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Authors and Affiliations

  1. Faculty of Health Sciences, Research Unit of Rheumatology, Department of Clinical Research, University of Southern Denmark, Odense University Hospital, J.B. Winsløws Vej 4, Indgang 96, 1. Sal, 5000, Odense, Denmark

    Dženan Mašić, Peter Junker, Robin Christensen & Torkell Ellingsen

  2. Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark

    Kristian Stengaard-Pedersen & Christian Ammitzbøll

  3. Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark

    Brian Bridal Løgstrup

  4. Musculoskeletal Statistics Unit, the Parker Institute, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark

    Robin Christensen

  5. Department of Rheumatology, King Christian 10th Hospital for Rheumatic Diseases, Gråsten, Denmark

    Kim Hørslev-Petersen

  6. South Jutland Hospital, Institute of Regional Health Services Research, University of Southern Denmark, Odense, Denmark

    Kim Hørslev-Petersen

  7. COPECARE and DANBIO, Rigshospitalet, Copenhagen, Denmark

    Merete Lund Hetland & Mikkel Østergaard

  8. Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

    Merete Lund Hetland & Mikkel Østergaard

  9. OPEN-Open Patient Data Explorative Network, Odense University Hospital, Odense, Denmark

    Sören Möller

  10. Department of Clinical Research, University of Southern Denmark, Odense, Denmark

    Sören Möller

  11. Diagnostik Center, Silkeborg Regional Hospital, Silkeborg, Denmark

    Dženan Mašić & Torkell Ellingsen

Authors
  1. Dženan Mašić
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  2. Kristian Stengaard-Pedersen
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  5. Merete Lund Hetland
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  7. Mikkel Østergaard
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  8. Christian Ammitzbøll
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Contributions

OPERA steering committee members (KS, KH, PJ, MH, MØ, TE) designed and conducted the OPERA Study. TE, KS, RC, BL and DM designed and planned the secondary analyses. TE, KS and DM obtained funding and ethical approval. RC, TE, KS, BL and DM designed the statistical analysis plan. SM and DM carried out the data analyses. DM had full access to the data and takes responsibility for the integrity of the data and for the accuracy of the data analysis. Additionally, all authors contributed to the interpretation of the results and reviewed and approved the final manuscript. DM drafted this article and is the guarantor. All authors contribution fulfils all 4 ICMJE criteria.

Corresponding author

Correspondence to Dženan Mašić.

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Conflict of interest

Dr. Masic has nothing to disclose. Dr. Stengaard-Pedersen has nothing to disclose. Dr. Løgstrup has nothing to disclose. Dr. Hørslev-Petersen has nothing to disclose. Dr. Hetland reports grants from Bristol-Myers Squibb, grants from AbbVie, grants from Roche, grants from Novartis, grants and personal fees from Merck, grants and personal fees from Biogen, grants and personal fees from Pfizer, personal fees from Eli Lilly, personal fees from Orion Pharma, personal fees from CellTrion, personal fees from Samsung Bioepsi, personal fees from Janssen Biologics B.V, personal fees from Diakonhjemmet Sykehus, personal fees from MSD, outside the submitted work; and I chair the sterring committee of the Danish Rheumatology Quality Registry (DANBIO), which receives public funding from the hospital owners and funding from pharmaceutical companies. I 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. Dr. Junker has nothing to disclose. Dr. Østergaard reports grants, personal fees and non-financial support from AbbVie, grants, personal fees and non-financial support 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, grants and personal fees from Celgene, personal fees from Sanofi, personal fees from Regeneron, grants, personal fees and non-financial support from Novartis, personal fees from Orion, personal fees from Hospira, outside the submitted work. Dr. Ammitzbøll has nothing to disclose. Dr. Möller has nothing to disclose. Dr. Christensen reports other from Lecture: Research Methods (Pfizer, DK; 2017), other from Lecture: GRADE Lecture (Celgene, DK; 2017), other from Ad Board Lecture: CAM (Orkla Health, DK; 2017), other from Project Grant: "GreenWhistle" (Mundipharma, 2019), other from Lecture: Diet in RMD (Novartis, DK; 2019), other from Consultancy Report: Network MA’s (Biogen, DK; 2017), other from Ad Board Lecture: GRADE (Lilly, DK; 2017), other from Consultancy Report: GRADE (Celgene, 2018), other from Lecture: Network MA's (LEO; 2020), outside the submitted work; and Musculoskeletal Statistics Unit, The Parker Institute is grateful for the financial support received from public and private foundations, companies and private individuals over the years. The Parker Institute is supported by a core grant from the Oak Foundation; The Oak Foundation is a group of philanthropic organizations that, since its establishment in 1983, has given grants to not-for-profit organizations around the world. Dr. Ellingsen has nothing to disclose.

Ethics approval

The study was approved by the Danish Data Protection Agency (2019-522-0133) and the Ethics Committee of the Central Denmark Region (1-10-72-436-17).

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Mašić, D., Stengaard-Pedersen, K., Løgstrup, B.B. et al. Similar lipid level changes in early rheumatoid arthritis patients following 1-year treat-to-target strategy with adalimumab plus methotrexate versus placebo plus methotrexate: secondary analyses from the randomised controlled OPERA trial. Rheumatol Int 41, 543–549 (2021). https://doi.org/10.1007/s00296-020-04756-5

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