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Research ArticleArticle

Biologic and Glucocorticoid Use after Methotrexate Initiation in Patients with Rheumatoid Arthritis

Michael D. George, Brian C. Sauer, Chia-Chen Teng, Grant W. Cannon, Bryant R. England, Gail S. Kerr, Ted R. Mikuls and Joshua F. Baker
The Journal of Rheumatology October 2018, jrheum.180178; DOI: https://doi.org/10.3899/jrheum.180178
Michael D. George
From the Philadelphia Veterans Affairs (VA) Medical Center and University of Pennsylvania, Philadelphia, Pennsylvania; Salt Lake City VA Medical Center and University of Utah, Salt Lake City, Utah; VA Nebraska-Western Iowa Health Care System and University of Nebraska Medical Center (UNMC), Omaha, Nebraska; DC VA Medical Center, Georgetown and Howard University, Washington, D.C., USA. Dr. George is supported by the Rheumatology Research Foundation Scientist Development Award. Dr. Cannon is supported by Specialty Care Center of Innovation, Veterans Health Administration, Department of Veterans Affairs. Dr. England is supported by the UNMC Physician-Scientist Training Program and UNMC Internal Medicine Scientist Development Award. Dr. Mikuls is supported through funding from a VA Merit Award (CX000896) and from the US National Institutes of Health (National Institute of General Medical Sciences grant U54-GM-115458). Dr. Baker is supported by a VA Clinical Science Research and Development Career Development Award (IK2 CX000955). Drs. Sauer and Cannon receive grant funding from Amgen for unrelated work. The contents of this work do not represent the views of the US Department of Veterans Affairs or the US government. M.D. George, MD, MSCE, University of Pennsylvania, VA Medical Center; B.C. Sauer, PhD, VA Medical Center, University of Utah; C.C. Teng, MS, VA Nebraska-Western Iowa Health Care System and University of Nebraska Medical Center; G.W. Cannon, MD, VA Medical Center, University of Utah; B.R. England, MD, VA Medical Center, University of Nebraska Medical Center; G.S. Kerr, MD, VA Medical Center, Georgetown and Howard Universities; T.R. Mikuls, MD, MSPH, VA Medical Center, University of Nebraska Medical Center; J.F. Baker, MD, MSCE, VA Medical Center, University of Pennsylvania. Address correspondence to Dr. M.D. George, Division of Rheumatology, 5 White Building, 3400 Spruce St., Philadelphia, Pennsylvania 19104, USA. E-mail: michael.george{at}uphs.upenn.edu. Accepted for publication July 18, 2018.
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Brian C. Sauer
From the Philadelphia Veterans Affairs (VA) Medical Center and University of Pennsylvania, Philadelphia, Pennsylvania; Salt Lake City VA Medical Center and University of Utah, Salt Lake City, Utah; VA Nebraska-Western Iowa Health Care System and University of Nebraska Medical Center (UNMC), Omaha, Nebraska; DC VA Medical Center, Georgetown and Howard University, Washington, D.C., USA. Dr. George is supported by the Rheumatology Research Foundation Scientist Development Award. Dr. Cannon is supported by Specialty Care Center of Innovation, Veterans Health Administration, Department of Veterans Affairs. Dr. England is supported by the UNMC Physician-Scientist Training Program and UNMC Internal Medicine Scientist Development Award. Dr. Mikuls is supported through funding from a VA Merit Award (CX000896) and from the US National Institutes of Health (National Institute of General Medical Sciences grant U54-GM-115458). Dr. Baker is supported by a VA Clinical Science Research and Development Career Development Award (IK2 CX000955). Drs. Sauer and Cannon receive grant funding from Amgen for unrelated work. The contents of this work do not represent the views of the US Department of Veterans Affairs or the US government. M.D. George, MD, MSCE, University of Pennsylvania, VA Medical Center; B.C. Sauer, PhD, VA Medical Center, University of Utah; C.C. Teng, MS, VA Nebraska-Western Iowa Health Care System and University of Nebraska Medical Center; G.W. Cannon, MD, VA Medical Center, University of Utah; B.R. England, MD, VA Medical Center, University of Nebraska Medical Center; G.S. Kerr, MD, VA Medical Center, Georgetown and Howard Universities; T.R. Mikuls, MD, MSPH, VA Medical Center, University of Nebraska Medical Center; J.F. Baker, MD, MSCE, VA Medical Center, University of Pennsylvania. Address correspondence to Dr. M.D. George, Division of Rheumatology, 5 White Building, 3400 Spruce St., Philadelphia, Pennsylvania 19104, USA. E-mail: michael.george{at}uphs.upenn.edu. Accepted for publication July 18, 2018.
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Chia-Chen Teng
From the Philadelphia Veterans Affairs (VA) Medical Center and University of Pennsylvania, Philadelphia, Pennsylvania; Salt Lake City VA Medical Center and University of Utah, Salt Lake City, Utah; VA Nebraska-Western Iowa Health Care System and University of Nebraska Medical Center (UNMC), Omaha, Nebraska; DC VA Medical Center, Georgetown and Howard University, Washington, D.C., USA. Dr. George is supported by the Rheumatology Research Foundation Scientist Development Award. Dr. Cannon is supported by Specialty Care Center of Innovation, Veterans Health Administration, Department of Veterans Affairs. Dr. England is supported by the UNMC Physician-Scientist Training Program and UNMC Internal Medicine Scientist Development Award. Dr. Mikuls is supported through funding from a VA Merit Award (CX000896) and from the US National Institutes of Health (National Institute of General Medical Sciences grant U54-GM-115458). Dr. Baker is supported by a VA Clinical Science Research and Development Career Development Award (IK2 CX000955). Drs. Sauer and Cannon receive grant funding from Amgen for unrelated work. The contents of this work do not represent the views of the US Department of Veterans Affairs or the US government. M.D. George, MD, MSCE, University of Pennsylvania, VA Medical Center; B.C. Sauer, PhD, VA Medical Center, University of Utah; C.C. Teng, MS, VA Nebraska-Western Iowa Health Care System and University of Nebraska Medical Center; G.W. Cannon, MD, VA Medical Center, University of Utah; B.R. England, MD, VA Medical Center, University of Nebraska Medical Center; G.S. Kerr, MD, VA Medical Center, Georgetown and Howard Universities; T.R. Mikuls, MD, MSPH, VA Medical Center, University of Nebraska Medical Center; J.F. Baker, MD, MSCE, VA Medical Center, University of Pennsylvania. Address correspondence to Dr. M.D. George, Division of Rheumatology, 5 White Building, 3400 Spruce St., Philadelphia, Pennsylvania 19104, USA. E-mail: michael.george{at}uphs.upenn.edu. Accepted for publication July 18, 2018.
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Grant W. Cannon
From the Philadelphia Veterans Affairs (VA) Medical Center and University of Pennsylvania, Philadelphia, Pennsylvania; Salt Lake City VA Medical Center and University of Utah, Salt Lake City, Utah; VA Nebraska-Western Iowa Health Care System and University of Nebraska Medical Center (UNMC), Omaha, Nebraska; DC VA Medical Center, Georgetown and Howard University, Washington, D.C., USA. Dr. George is supported by the Rheumatology Research Foundation Scientist Development Award. Dr. Cannon is supported by Specialty Care Center of Innovation, Veterans Health Administration, Department of Veterans Affairs. Dr. England is supported by the UNMC Physician-Scientist Training Program and UNMC Internal Medicine Scientist Development Award. Dr. Mikuls is supported through funding from a VA Merit Award (CX000896) and from the US National Institutes of Health (National Institute of General Medical Sciences grant U54-GM-115458). Dr. Baker is supported by a VA Clinical Science Research and Development Career Development Award (IK2 CX000955). Drs. Sauer and Cannon receive grant funding from Amgen for unrelated work. The contents of this work do not represent the views of the US Department of Veterans Affairs or the US government. M.D. George, MD, MSCE, University of Pennsylvania, VA Medical Center; B.C. Sauer, PhD, VA Medical Center, University of Utah; C.C. Teng, MS, VA Nebraska-Western Iowa Health Care System and University of Nebraska Medical Center; G.W. Cannon, MD, VA Medical Center, University of Utah; B.R. England, MD, VA Medical Center, University of Nebraska Medical Center; G.S. Kerr, MD, VA Medical Center, Georgetown and Howard Universities; T.R. Mikuls, MD, MSPH, VA Medical Center, University of Nebraska Medical Center; J.F. Baker, MD, MSCE, VA Medical Center, University of Pennsylvania. Address correspondence to Dr. M.D. George, Division of Rheumatology, 5 White Building, 3400 Spruce St., Philadelphia, Pennsylvania 19104, USA. E-mail: michael.george{at}uphs.upenn.edu. Accepted for publication July 18, 2018.
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Bryant R. England
From the Philadelphia Veterans Affairs (VA) Medical Center and University of Pennsylvania, Philadelphia, Pennsylvania; Salt Lake City VA Medical Center and University of Utah, Salt Lake City, Utah; VA Nebraska-Western Iowa Health Care System and University of Nebraska Medical Center (UNMC), Omaha, Nebraska; DC VA Medical Center, Georgetown and Howard University, Washington, D.C., USA. Dr. George is supported by the Rheumatology Research Foundation Scientist Development Award. Dr. Cannon is supported by Specialty Care Center of Innovation, Veterans Health Administration, Department of Veterans Affairs. Dr. England is supported by the UNMC Physician-Scientist Training Program and UNMC Internal Medicine Scientist Development Award. Dr. Mikuls is supported through funding from a VA Merit Award (CX000896) and from the US National Institutes of Health (National Institute of General Medical Sciences grant U54-GM-115458). Dr. Baker is supported by a VA Clinical Science Research and Development Career Development Award (IK2 CX000955). Drs. Sauer and Cannon receive grant funding from Amgen for unrelated work. The contents of this work do not represent the views of the US Department of Veterans Affairs or the US government. M.D. George, MD, MSCE, University of Pennsylvania, VA Medical Center; B.C. Sauer, PhD, VA Medical Center, University of Utah; C.C. Teng, MS, VA Nebraska-Western Iowa Health Care System and University of Nebraska Medical Center; G.W. Cannon, MD, VA Medical Center, University of Utah; B.R. England, MD, VA Medical Center, University of Nebraska Medical Center; G.S. Kerr, MD, VA Medical Center, Georgetown and Howard Universities; T.R. Mikuls, MD, MSPH, VA Medical Center, University of Nebraska Medical Center; J.F. Baker, MD, MSCE, VA Medical Center, University of Pennsylvania. Address correspondence to Dr. M.D. George, Division of Rheumatology, 5 White Building, 3400 Spruce St., Philadelphia, Pennsylvania 19104, USA. E-mail: michael.george{at}uphs.upenn.edu. Accepted for publication July 18, 2018.
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Gail S. Kerr
From the Philadelphia Veterans Affairs (VA) Medical Center and University of Pennsylvania, Philadelphia, Pennsylvania; Salt Lake City VA Medical Center and University of Utah, Salt Lake City, Utah; VA Nebraska-Western Iowa Health Care System and University of Nebraska Medical Center (UNMC), Omaha, Nebraska; DC VA Medical Center, Georgetown and Howard University, Washington, D.C., USA. Dr. George is supported by the Rheumatology Research Foundation Scientist Development Award. Dr. Cannon is supported by Specialty Care Center of Innovation, Veterans Health Administration, Department of Veterans Affairs. Dr. England is supported by the UNMC Physician-Scientist Training Program and UNMC Internal Medicine Scientist Development Award. Dr. Mikuls is supported through funding from a VA Merit Award (CX000896) and from the US National Institutes of Health (National Institute of General Medical Sciences grant U54-GM-115458). Dr. Baker is supported by a VA Clinical Science Research and Development Career Development Award (IK2 CX000955). Drs. Sauer and Cannon receive grant funding from Amgen for unrelated work. The contents of this work do not represent the views of the US Department of Veterans Affairs or the US government. M.D. George, MD, MSCE, University of Pennsylvania, VA Medical Center; B.C. Sauer, PhD, VA Medical Center, University of Utah; C.C. Teng, MS, VA Nebraska-Western Iowa Health Care System and University of Nebraska Medical Center; G.W. Cannon, MD, VA Medical Center, University of Utah; B.R. England, MD, VA Medical Center, University of Nebraska Medical Center; G.S. Kerr, MD, VA Medical Center, Georgetown and Howard Universities; T.R. Mikuls, MD, MSPH, VA Medical Center, University of Nebraska Medical Center; J.F. Baker, MD, MSCE, VA Medical Center, University of Pennsylvania. Address correspondence to Dr. M.D. George, Division of Rheumatology, 5 White Building, 3400 Spruce St., Philadelphia, Pennsylvania 19104, USA. E-mail: michael.george{at}uphs.upenn.edu. Accepted for publication July 18, 2018.
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Ted R. Mikuls
From the Philadelphia Veterans Affairs (VA) Medical Center and University of Pennsylvania, Philadelphia, Pennsylvania; Salt Lake City VA Medical Center and University of Utah, Salt Lake City, Utah; VA Nebraska-Western Iowa Health Care System and University of Nebraska Medical Center (UNMC), Omaha, Nebraska; DC VA Medical Center, Georgetown and Howard University, Washington, D.C., USA. Dr. George is supported by the Rheumatology Research Foundation Scientist Development Award. Dr. Cannon is supported by Specialty Care Center of Innovation, Veterans Health Administration, Department of Veterans Affairs. Dr. England is supported by the UNMC Physician-Scientist Training Program and UNMC Internal Medicine Scientist Development Award. Dr. Mikuls is supported through funding from a VA Merit Award (CX000896) and from the US National Institutes of Health (National Institute of General Medical Sciences grant U54-GM-115458). Dr. Baker is supported by a VA Clinical Science Research and Development Career Development Award (IK2 CX000955). Drs. Sauer and Cannon receive grant funding from Amgen for unrelated work. The contents of this work do not represent the views of the US Department of Veterans Affairs or the US government. M.D. George, MD, MSCE, University of Pennsylvania, VA Medical Center; B.C. Sauer, PhD, VA Medical Center, University of Utah; C.C. Teng, MS, VA Nebraska-Western Iowa Health Care System and University of Nebraska Medical Center; G.W. Cannon, MD, VA Medical Center, University of Utah; B.R. England, MD, VA Medical Center, University of Nebraska Medical Center; G.S. Kerr, MD, VA Medical Center, Georgetown and Howard Universities; T.R. Mikuls, MD, MSPH, VA Medical Center, University of Nebraska Medical Center; J.F. Baker, MD, MSCE, VA Medical Center, University of Pennsylvania. Address correspondence to Dr. M.D. George, Division of Rheumatology, 5 White Building, 3400 Spruce St., Philadelphia, Pennsylvania 19104, USA. E-mail: michael.george{at}uphs.upenn.edu. Accepted for publication July 18, 2018.
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Joshua F. Baker
From the Philadelphia Veterans Affairs (VA) Medical Center and University of Pennsylvania, Philadelphia, Pennsylvania; Salt Lake City VA Medical Center and University of Utah, Salt Lake City, Utah; VA Nebraska-Western Iowa Health Care System and University of Nebraska Medical Center (UNMC), Omaha, Nebraska; DC VA Medical Center, Georgetown and Howard University, Washington, D.C., USA. Dr. George is supported by the Rheumatology Research Foundation Scientist Development Award. Dr. Cannon is supported by Specialty Care Center of Innovation, Veterans Health Administration, Department of Veterans Affairs. Dr. England is supported by the UNMC Physician-Scientist Training Program and UNMC Internal Medicine Scientist Development Award. Dr. Mikuls is supported through funding from a VA Merit Award (CX000896) and from the US National Institutes of Health (National Institute of General Medical Sciences grant U54-GM-115458). Dr. Baker is supported by a VA Clinical Science Research and Development Career Development Award (IK2 CX000955). Drs. Sauer and Cannon receive grant funding from Amgen for unrelated work. The contents of this work do not represent the views of the US Department of Veterans Affairs or the US government. M.D. George, MD, MSCE, University of Pennsylvania, VA Medical Center; B.C. Sauer, PhD, VA Medical Center, University of Utah; C.C. Teng, MS, VA Nebraska-Western Iowa Health Care System and University of Nebraska Medical Center; G.W. Cannon, MD, VA Medical Center, University of Utah; B.R. England, MD, VA Medical Center, University of Nebraska Medical Center; G.S. Kerr, MD, VA Medical Center, Georgetown and Howard Universities; T.R. Mikuls, MD, MSPH, VA Medical Center, University of Nebraska Medical Center; J.F. Baker, MD, MSCE, VA Medical Center, University of Pennsylvania. Address correspondence to Dr. M.D. George, Division of Rheumatology, 5 White Building, 3400 Spruce St., Philadelphia, Pennsylvania 19104, USA. E-mail: michael.george{at}uphs.upenn.edu. Accepted for publication July 18, 2018.
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Abstract

Objective Biologic therapies can improve disease control for patients with rheumatoid arthritis (RA) but may be both overused and underused. We aimed to identify predictors of greater use of biologic therapies and to identify factors associated with persistent glucocorticoid use.

Methods Using national US Veteran’s Affairs databases 2005–2016, we identified patients with RA receiving a first-ever prescription of methotrexate (MTX), requiring ≥ 6 months of baseline data. We evaluated predictors of biologic therapy initiation within 2 years of starting MTX and factors associated with baseline and persistent glucocorticoid use at 6–12 months using multivariable models.

Results Among 17,415 patients starting MTX, 3263 patients received biologic therapy within 2 years (20.6% 2-yr incidence). In adjusted analyses, biologic use was substantially lower in older patients [e.g., aHR 0.20 (95% CI 0.16, 0.26) for patients ≥ 80 vs < 50] and patients with more comorbidities [aHR 0.79 (95% CI 0.72, 0.87) for Charlson score ≥ 3 vs < 3]. Patients with heart failure [aHR 0.68 (95% CI 0.54, 0.84)], cancer [aHR 0.78 (95% CI 0.66, 0.92)], or who were nonwhite [aHR 0.79 (95% CI 0.72, 0.87)] were also less likely to receive a biologic. In contrast, baseline and persistent glucocorticoid use was similar across age groups and more common in patients with greater comorbidity.

Conclusion Biologic therapy is initiated less frequently in patients with RA who are older, have more comorbidities, and who are nonwhite. While biologics may be avoided in older and sicker patients because of safety concerns, glucocorticoid use is similar regardless of age and is more frequent in patients with comorbidities, with implications for patient outcomes.

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The Journal of Rheumatology: 52 (12)
The Journal of Rheumatology
Vol. 52, Issue 12
1 Dec 2025
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Biologic and Glucocorticoid Use after Methotrexate Initiation in Patients with Rheumatoid Arthritis
Michael D. George, Brian C. Sauer, Chia-Chen Teng, Grant W. Cannon, Bryant R. England, Gail S. Kerr, Ted R. Mikuls, Joshua F. Baker
The Journal of Rheumatology Oct 2018, jrheum.180178; DOI: 10.3899/jrheum.180178

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Biologic and Glucocorticoid Use after Methotrexate Initiation in Patients with Rheumatoid Arthritis
Michael D. George, Brian C. Sauer, Chia-Chen Teng, Grant W. Cannon, Bryant R. England, Gail S. Kerr, Ted R. Mikuls, Joshua F. Baker
The Journal of Rheumatology Oct 2018, jrheum.180178; DOI: 10.3899/jrheum.180178
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