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Short-term dose and duration-dependent glucocorticoid risk for cardiovascular events in glucocorticoid-naive patients with rheumatoid arthritis
  1. Anthony James Ocon1,
  2. George Reed2,3,
  3. Dimitrios A Pappas3,4,5,
  4. Jeffrey R Curtis6,
  5. Joel M Kremer3,5,7
  1. 1Medicine and Allergy, Immunology, Rheumatology, University of Rochester Medical Center, Rochester, New York, USA
  2. 2Medicine, Preventative and Behavioral Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA
  3. 3Corrona Research Foundation, LLC, Waltham, MA, USA
  4. 4Medicine and Rheumatology, Columbia University, New York, New York, USA
  5. 5CorEvitas (formerly CORRONA), LCC, Waltham, Massachusetts, USA
  6. 6Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA
  7. 7Medicine and Rheumatology, Albany Medical College, The Center for Rheumatology, LLC, Albany, New York, USA
  1. Correspondence to Dr Anthony James Ocon, Allergy, Immunology, Rheumatology, University of Rochester Medical Center, Rochester, NY 14642, USA; anthony.ocon{at}gmail.com

Abstract

Objectives Rheumatoid arthritis (RA), along with glucocorticoid use, is associated with cardiovascular disease. Cardiovascular safety of glucocorticoids in RA is controversial and may be related to dose and duration of use. We determined if initiating glucocorticoids in steroid-naive RA patients would increase cardiovascular event (CVE) risk in a dose and duration-dependent manner over short-term intervals.

Methods Patients enrolled in CorEvitas (formerly Corrona) RA registry. Cox proportional-hazards models estimated adjusted HRs (aHR) for incident CVE in patients who initiated glucocorticoid treatment, adjusting for RA duration, traditional cardiovascular risk factors and time-varying covariates: Clinical Disease activity Index, disease-modifying antirheumatic drugs use and prednisone-equivalent use. Glucocorticoid use assessed current daily dose, cumulative dose and duration of use over rolling intervals of preceding 6 months and 1 year.

Results 19 902 patients met criteria. 1106 CVE occurred (1.66/100 person-years). Increased aHR occurred at current doses of ≥5–9 mg 1.56 (1.18–2.06) and ≥10 mg 1.91 (1.31–2.79), without increased risk at 0–4 mg 1.04 (0.55–1.59). Cumulative dose over preceding 6 months showed increased aHR at 751–1100 mg 1.43 (1.04–1.98) and >1100 mg 2.05 (1.42–2.94), without increased risk at lower doses; duration of use over preceding 6 months exhibited increased aHR for >81 days of use 1.54 (1.08–2.32), without increased risk at shorter durations. One-year analyses were consistent.

Conclusions Over preceding 6-month and 1-year intervals, initiating glucocorticoids in steroid-naïve RA patients is associated with increased risk of CVE at daily doses ≥5 mg and increased cumulative dose and duration of use. No association with risk for CVE was found with daily prednisone of ≤4 mg or shorter cumulative doses and durations.

  • Arthritis
  • Rheumatoid
  • Cardiovascular Diseases
  • Glucocorticoids

Data availability statement

Data may be obtained from a third party and are not publicly available. Deidentified participant data may be obtained from CorEvitas (formerly Corrona) and are not publicly available. Reuse only with permission from CorEvitas. Contact: info@corevitas.com

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Data availability statement

Data may be obtained from a third party and are not publicly available. Deidentified participant data may be obtained from CorEvitas (formerly Corrona) and are not publicly available. Reuse only with permission from CorEvitas. Contact: info@corevitas.com

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Footnotes

  • Handling editor Josef S Smolen

  • Contributors AJO and JMK designed the study. Statistical analysis by GR. All authors (AJO, GR, DAP, JRC and JMK) participated in data interpretation, writing, editing and final approval.

  • Funding The investigation was funded by the Corrona Research Foundation, a not for profit, 501(C)(3) independent charitable foundation, with no industry financial ties

  • Competing interests AJO has no financial conflicts of interest. GR and JMK are consultants for Corrona, LLC. GR is a consultant for the Corrona Research Foundation (CRF), while JMK is an officer of the CRF who serves without any form of remuneration. The CRF is a not for profit, 501(C)(3) independent charitable foundation, with no industry financial ties. DAP is an employee and shareholder of Corrona, and a consultant for Regeneron, Novartis and Roche (unrelated work), and is a member of the board of directors for CFR. JRC has research grants and/or consulting from Abbvie, Amgen, Corrona, Janssen, Lilly, Pfizer, Sanofi (for unrelated work).

  • Patient and public involvement statement Patients were involved upon signing informed consent to participate in the registry, understanding that information would be recorded longitudinally and used for a variety of research outcomes that could be relevant to care. Patients were informed about the time required to complete forms at each visit. Outcomes of CorEvitas studies are shared with patients when viewed as potentially impacting their welfare. Patients were not involved in the design of or recruitment for this study.

  • 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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