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Hydroxychloroquine dosing in immune-mediated diseases: implications for patient safety

  • Safety and Pharmacovigilance
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A Correction to this article was published on 22 December 2017

This article has been updated

Abstract

Evidence suggests that hydroxychloroquine (HCQ) retinal toxicity is more common than previously thought. Adhering to careful weight-based dosing can significantly reduce the risk of this adverse event and is recommended in recent guidelines. We used electronic health record data from a large health system to examine HCQ dosing over a 5-year period and identify risk factors associated with higher dosage of HCQ. We constructed a longitudinal, retrospective cohort of patients with HCQ prescriptions (1681 patients with 3490 prescribing events) between 2012 and 2016. We measured HCQ dosing patterns relative to guidelines (<6.5 and <5.0 mg/kg) over time and used longitudinal multivariate mixed effects logistic regression to identify sociodemographic, clinical and health system factors associated with receiving higher than recommended doses of HCQ. The proportion of patients receiving doses above 6.5 mg/kg decreased from 12% in 2012 to 7% by 2016. Similarly, the proportion of patients with doses above 5.0 mg/kg fell from 38% in 2012 to 30% in 2016. Low body weight (<68 kg) was strongly associated with receiving doses of HCQ above 6.5 mg/kg across all time points, even after adjusting for other factors (odds ratios ranging from 13.2 to 21.0). Although the proportion of patients receiving higher than recommended HCQ doses has declined over a period of 5 years, a substantial number of individuals remain at increased risk for toxicity. Given the widespread use of HCQ in immune-mediated diseases, our study suggests that interventions aimed to ensure appropriate dosing are warranted to improve patient safety.

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Change history

  • 22 December 2017

    The given and family name of a co-author R. Adams Dudley was swapped in the published article. The correct given name is R. Adams and the family name is Dudley.

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Acknowledgements

We thank Chris Tonner and Dana Ludwig for their technical assistance with this project.

Author information

Authors and Affiliations

  1. Division of Rheumatology, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA, 94143, USA

    Milena A. Gianfrancesco, Gabriela Schmajuk, Laura Trupin, Kashif Jafri & Jinoos Yazdany

  2. Veterans Affairs Medical Center, San Francisco, San Francisco, USA

    Gabriela Schmajuk

  3. Department of Medicine, California Pacific Medical Center, San Francisco, USA

    Sarah Haserodt

  4. Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, USA

    Zara Izadi & Stephen Shiboski

  5. Institute for Computational Health Sciences, University of California, San Francisco, San Francisco, USA

    Marina Sirota

  6. Center for Healthcare Value, Philip R. Lee Institute for Health Policy Studies, University of California, San Francisco, San Francisco, USA

    R. Adams Dudley

Authors
  1. Milena A. Gianfrancesco
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  2. Gabriela Schmajuk
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  3. Sarah Haserodt
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  4. Laura Trupin
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  5. Zara Izadi
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  6. Kashif Jafri
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  7. Stephen Shiboski
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  8. Marina Sirota
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  9. R. Adams Dudley
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  10. Jinoos Yazdany
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Corresponding author

Correspondence to Milena A. Gianfrancesco.

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Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study formal consent is not required.

Funding

This work is supported by AHRQ R01 HS024412 (JY) and NIAMS K23 AR063770 (GS). Dr. Gianfrancesco has received funding from the Rheumatology Research Foundation. Dr. Yazdany is supported by the Robert L. Kroc Endowed Chair in Rheumatic and Connective Tissue Disorders. Drs. Yazdany and Schmajuk are also supported by the Russell/Engleman Medical Research Center for Arthritis. Dr. Sirota is funded in part by the March of Dimes Prematurity Research Center. Dr. Jafri is supported by an NIH T32 grant 5T32AR007304-38. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Agency for Healthcare Research and Quality, National Institute of Arthritis and Musculoskeletal and Skin Diseases, or National Institutes of Health.

Conflict of interest

All authors report no conflicts of interest regarding this manuscript.

Additional information

A correction to this article is available online at https://doi.org/10.1007/s00296-017-3918-8.

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Gianfrancesco, M.A., Schmajuk, G., Haserodt, S. et al. Hydroxychloroquine dosing in immune-mediated diseases: implications for patient safety. Rheumatol Int 37, 1611–1618 (2017). https://doi.org/10.1007/s00296-017-3782-6

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  • DOI: https://doi.org/10.1007/s00296-017-3782-6

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