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Comparative risk of osteoporotic fracture among patients with rheumatoid arthritis receiving TNF inhibitors versus other biologics: a cohort study

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Abstract

Summary

In this population-based cohort study on comparative osteoporotic fracture risks between different biologic disease-modifying drugs among patients with rheumatoid arthritis (RA), we did not find a significant difference in the risk of osteoporotic fractures between RA patients receiving TNF inhibitors versus abatacept or tocilizumab.

Introduction

We aimed to investigate the comparative risk of osteoporotic fractures between rheumatoid arthritis (RA) patients who initiated TNF inhibitors (TNFis) versus abatacept or tocilizumab.

Methods

Using the Korea National Health Insurance Service datasets from 2002 to 2016, RA patients who initiated TNFis, abatacept, or tocilizumab were identified. The primary outcome was a composite end point of non-vertebral fractures and hospitalized vertebral fractures; secondary outcomes were two components of the primary outcome and fractures occurring at the humerus/forearm. Propensity score (PS) matching with a variable ratio up to 10 TNFi initiators per 1 comparator drug initiator was used to adjust for > 50 baseline confounders. We estimated hazard ratios (HRs) and 95% confidence interval (CI) of fractures comparing TNFi initiators to abatacept and to tocilizumab by Cox proportional hazard models stratified by a matching ratio.

Results

After PS-matching, 2307 TNFi initiators PS-matched on 588 abatacept initiators, and 2462 TNFi initiators on 640 tocilizumab initiators were included. A total of 77 fractures occurred during a mean follow-up of 454 days among TNFi and abatacept initiators and 83 fractures during 461 days among TNFi and tocilizumab initiators. The PS-matched HR (95% CI) was 0.91 (0.48–1.71) comparing TNFi versus abatacept initiators, and 1.00 (0.55–1.83) comparing TNFi versus tocilizumab initiators. Analysis on vertebral and non-vertebral fractures showed similar results.

Conclusions

In this nationally representative cohort, we did not find a significant difference in the risk of fractures between TNFi initiators versus abatacept or tocilizumab among RA patients.

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Availability of data and material

The raw datasets were obtained from Korea National Health Insurance Service (https://nhiss.nhis.or.kr/), but restrictions apply to the availability of these data. Data are, however, available from the authors upon reasonable request and with permission of Korea National Health Insurance Service.

Abbreviations

bDMARD:

biologic DMARD

BMD:

bone mineral density

CI:

confidence interval

DMARD:

disease modifying anti-rheumatic drug

HR:

hazard ratio

ICD10:

International Classification of Disease Tenth Revision

KNHIS:

Korea National Health Insurance Service

MTX:

methotrexate

nbDMARD:

non-biologic DMARD

PS:

propensity score

RA:

rheumatoid arthritis

SD:

standard deviation

TNFi:

TNF inhibitor

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Funding

This study was supported by an investigator sponsored grant from Celltrion healthcare company (06–2017-138) and Hanmi Pharmaceutical Company (06–2018-064). The funding source had no influence on the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication.

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Author notes

  1. A. Shin and E.H. Park contributed equally to this work.

Authors and Affiliations

  1. Division of Rheumatology Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea

    A. Shin, E.H. Park, Y.-J. Ha, Y.J. Lee & E.H. Kang

  2. Faculty of Pharmacy School of Pharmaceutical Science, National Yang-Ming University, Taipei, Taiwan

    Y.-H. Dong

  3. Institute of Public Health, School of Medicine, National Yang-Ming University, Taipei, Taiwan

    Y.-H. Dong

  4. Division of Rheumatology, Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea

    E.B. Lee & Y.W. Song

  5. Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology and College of Medicine, Seoul National University, Seoul, South Korea

    Y.W. Song

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Correspondence to E.H. Kang.

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Conflicts of interest

Anna Shin, Eun Hye Park, Yaa-Hui Dong, You-Jung Ha, Yun Jong Lee, Eun Bong Lee, Yeong Wook Song, and Eun Ha Kang declare that they have no conflict of interest.

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Institutional Review Boards of Seoul National University Hospital approved the study protocol and privacy precautions (X-1706-405-902).

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Waived because we used de-identified dataset.

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Shin, A., Park, E., Dong, YH. et al. Comparative risk of osteoporotic fracture among patients with rheumatoid arthritis receiving TNF inhibitors versus other biologics: a cohort study. Osteoporos Int 31, 2131–2139 (2020). https://doi.org/10.1007/s00198-020-05488-9

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