Michael D. George, MD, MSCE; Joshua F. Baker, MD, MSCE; Kevin Winthrop, MD, MPH; Evo Alemao, RPh, PhD; Lang Chen, PhD; Sean Connolly, PhD; Jesse Y. Hsu, PhD; Teresa A. Simon, MPH; Qufei Wu, MS; Fenglong Xie, MS; Shuo Yang, MS; Jeffrey R. Curtis, MD, MS, MPH
Financial Support: Dr. George is supported by the Rheumatology Research Foundation Scientist Development Award and grant 1K23AR073931-01 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Curtis is supported by grant PPRND-1507-32163 from the Patient-Centered Outcomes Research Institute. This study also received funding from Bristol-Myers Squibb.
Disclosures: Dr. George reports grants from the Rheumatology Research Foundation, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and Bristol-Myers Squibb and personal fees from AbbVie outside the submitted work. Dr. Baker reports personal fees from Bristol-Myers Squibb and Burns White and grants from the Veterans Affairs Office of Research and Development and the American Federation for Aging Research outside the submitted work. Dr. Winthrop reports grants and personal fees from Pfizer, Bristol-Myers Squibb, and UCB and personal fees from AbbVie, Lilly, Galapagos, and GSK outside the submitted work. Dr. Alemao reports that he is an employee and shareholder of Bristol-Myers Squibb. Dr. Connolly reports that he is an employee of and holds stock in Bristol-Myers Squibb. Ms. Simon reports employment with Bristol-Myers Squibb. Dr. Curtis reports grants and personal fees from Bristol-Myers Squibb during the conduct of the study and grants and personal fees from AbbVie, Amgen, Corrona, Janssen, Lilly, Myriad, Pfizer, UCB, and Regeneron outside the submitted work. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M18-2217.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that her spouse has stock options/holdings with Targeted Diagnostics and Therapeutics. Darren B. Taichman, MD, PhD, Executive Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Catharine B. Stack, PhD, MS, Deputy Editor, Statistics, reports that she has stock holdings in Pfizer, Johnson & Johnson, and Colgate-Palmolive. Christina C. Wee, MD, MPH, Deputy Editor, reports employment with Beth Israel Deaconess Medical Center. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Yu-Xiao Yang, MD, MSCE, Deputy Editor, reports that he has no financial relationships or interest to disclose.
Reproducible Research Statement:Study protocol: See Part 2 of the Supplement. Statistical code: Available from Dr. George (e-mail, firstname.lastname@example.org). Data set: Data use is governed by data use agreements. Medicare data are available through the Centers for Medicare & Medicaid Services. MarketScan data are available to license through IBM.
Corresponding Author: Michael D. George, MD, MSCE, Division of Rheumatology, 5 White Building, 3400 Spruce Street, Philadelphia, PA 19104; e-mail, email@example.com.
Current Author Addresses: Drs. George and Baker: Division of Rheumatology, 5 White Building, 3400 Spruce Street, Philadelphia, PA 19104.
Dr. Winthrop: 3181 SW Sam Jackson Park Road, Portland, OR 97239.
Drs. Alemao and Connolly and Ms. Simon: 345 Park Avenue, New York, NY 10154.
Drs. Chen and Curtis, Mr. Xie, and Mr. Yang: Faculty Offices Tower, Room 802, 510 20th Street South, Birmingham, AL 35294.
Dr. Hsu and Mr. Wu: Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104.
Author Contributions: Conception and design: M.D. George, J.F. Baker, K. Winthrop, E. Alemao, L. Chen, T.A. Simon, F. Xie, J.R. Curtis.
Analysis and interpretation of the data: M.D. George, J.F. Baker, K. Winthrop, E. Alemao, L. Chen, S. Connolly, T.A. Simon, Q. Wu, F. Xie, S. Yang, J.R. Curtis.
Drafting of the article: M.D. George, J.F. Baker, T.A. Simon, J.R. Curtis.
Critical revision of the article for important intellectual content: M.D. George, J.F. Baker, K. Winthrop, L. Chen, J.R. Curtis.
Final approval of the article: M.D. George, J.F. Baker, K. Winthrop, E. Alemao, L. Chen, S. Connolly, J.Y. Hsu, T.A. Simon, Q. Wu, F. Xie, S. Yang, J.R. Curtis.
Statistical expertise: J.F. Baker, K. Winthrop, J.Y. Hsu, T.A. Simon, F. Xie, S. Yang.
Obtaining of funding: M.D. George, E. Alemao, T.A. Simon.
Administrative, technical, or logistic support: J.F. Baker, K. Winthrop, J.R. Curtis.
Collection and assembly of data: M.D. George.
Patients with rheumatoid arthritis (RA) are at increased risk for infection after arthroplasty, yet risks of specific biologic medications are unknown.
To compare risk for postoperative infection among biologics and to evaluate the risk associated with glucocorticoids.
Retrospective cohort study.
Medicare and Truven MarketScan administrative data from January 2006 through September 2015.
Adults with RA who were having elective inpatient total knee or hip arthroplasty, either primary or revision, and had a recent infusion of or prescription for abatacept, adalimumab, etanercept, infliximab, rituximab, or tocilizumab before surgery.
Propensity-adjusted analyses using inverse probability weights evaluated comparative risks for hospitalized infection within 30 days and prosthetic joint infection (PJI) within 1 year after surgery between biologics or with different dosages of glucocorticoids. Secondary analyses evaluated non–urinary tract hospitalized infections and 30-day readmissions.
Among 9911 patients treated with biologics, 10 923 surgical procedures were identified. Outcomes were similar in patients who received different biologics. Compared with an 8.16% risk for hospitalized infection with abatacept, predicted risk from propensity-weighted models ranged from 6.87% (95% CI, 5.30% to 8.90%) with adalimumab to 8.90% (CI, 5.70% to 13.52%) with rituximab. Compared with a 2.14% 1-year cumulative incidence of PJI with abatacept, predicted incidence ranged from 0.35% (CI, 0.11% to 1.12%) with rituximab to 3.67% (CI, 1.69% to 7.88%) with tocilizumab. Glucocorticoids were associated with a dose-dependent increase in postoperative risk for all outcomes. Propensity-weighted models showed that use of more than 10 mg of glucocorticoids per day (vs. no glucocorticoid use) resulted in a predicted risk for hospitalized infection of 13.25% (CI, 9.72% to 17.81%) (vs. 6.78%) and a predicted 1-year cumulative incidence of PJI of 3.83% (CI, 2.13% to 6.87%) (vs. 2.09%).
Residual confounding is possible, and sample sizes for rituximab and tocilizumab were small.
Risks for hospitalized infection, PJI, and readmission after arthroplasty were similar across biologics. In contrast, glucocorticoid use, especially with dosages above 10 mg/d, was associated with greater risk for adverse outcomes.
Rheumatology Research Foundation, National Institutes of Health, and Bristol-Myers Squibb.
George MD, Baker JF, Winthrop K, et al. Risk of Biologics and Glucocorticoids in Patients With Rheumatoid Arthritis Undergoing Arthroplasty: A Cohort Study. Ann Intern Med. 2019;170:825–836. [Epub ahead of print 21 May 2019]. doi: https://doi.org/10.7326/M18-2217
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Published: Ann Intern Med. 2019;170(12):825-836.
Published at www.annals.org on 21 May 2019
Endocrine and Metabolism, Healthcare Delivery and Policy, Hospital Medicine, Rheumatoid Arthritis, Rheumatology.
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Print ISSN: 0003-4819 | Online ISSN: 1539-3704
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