title: Safety of Biologic and Nonbiologic Disease-modifying Antirheumatic Drug Therapy in Veterans with Rheumatoid Arthritis and Hepatitis C Virus Infection.
abstract: To examine the effect of disease-modifying antirheumatic drug (DMARD) therapy on hepatotoxicity among patients with rheumatoid arthritis (RA) and hepatitis C virus (HCV) infection.
  
  
  
  We identified biologic and nonbiologic treatment episodes of patients with RA using the 1997-2011 national data from the US Veterans Health Administration. Eligible episodes had HCV infection (defined by detectable HCV RNA) and subsequently initiated a new biologic or nonbiologic DMARD. Cohort entry required a baseline alanine aminotransferase (ALT) < 66 IU/l and quantifiable HCV RNA within 90 days prior to starting biologic/DMARD therapy. The primary outcome of interest was hepatotoxicity, defined as ALT elevation ≥ 100 IU/l or increase in HCV RNA of 1 log or more, and was examined within the first year of biologic/DMARD use. Results were reported as the cumulative incidence of treatment episodes achieving predefined hepatotoxicity at 3, 6, and 12 months after biologic/DMARD initiation.
  
  
  
  RA patients with HCV (n = 748) were identified and contributed 1097 biologic/DMARD treatment episodes. Overall, ALT elevations were uncommon, with 37 (3.4%) hepatotoxicity events occurring within 12 months. Treatment episodes with biologic DMARD demonstrated more frequency of hepatotoxicity than did nonbiologic DMARD (4.8% vs 2.3%, p = 0.03). Among treatment episodes involving hepatotoxicity events, the majority occurred within 6 months of DMARD initiation (29/37, 78%).
  
  
  
  In US veterans with HCV and RA receiving biologic and nonbiologic DMARD, the frequency of hepatotoxicity (ALT ≥ 100 IU/l) was low, with a higher frequency observed in treatment episodes with current biologic use.
authors.affiliation: From the Veterans Affairs (VA) Medical Center; Department of Medicine, Division of Infectious Diseases, University of Mississippi Medical Center, Jackson, Mississippi; Birmingham VA Medical Center (VAMC); Department of Medicine, Division of Rheumatology, University of Alabama at Birmingham; Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, Alabama; VA Nebraska-Western Iowa Health Care System and University of Nebraska Medical Center, Omaha, Nebraska; Oregon Health Sciences University, Portland, Oregon, USA. Mary.burton2@va.gov.|M.J. Burton, MD, Associate Professor, VA Medical Center, and Department of Medicine, Division of Infectious Diseases, University of Mississippi Medical Center; J.R. Curtis, MD, Professor, Birmingham VAMC, and Department of Medicine, Division of Rheumatology, University of Alabama at Birmingham; S. Yang, MS, Birmingham VAMC; L. Chen, PhD, Department of Medicine, Division of Rheumatology, University of Alabama at Birmingham; J.A. Singh, MBBS, MPH, Professor, Birmingham VAMC, and Department of Medicine, Division of Rheumatology, University of Alabama at Birmingham; T.R. Mikuls, MD, MSPH, Professor, VA Nebraska-Western Iowa Health Care System and University of Nebraska Medical Center; K.L. Winthrop, MD, Professor, Oregon Health Sciences University; J.W. Baddley, MD, Professor, Birmingham VAMC, and Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham. Mary.burton2@va.gov.
authors.forename: Mary Jane
authors.initials: MJ
authors.lastname: Burton
authors.affiliation: From the Veterans Affairs (VA) Medical Center; Department of Medicine, Division of Infectious Diseases, University of Mississippi Medical Center, Jackson, Mississippi; Birmingham VA Medical Center (VAMC); Department of Medicine, Division of Rheumatology, University of Alabama at Birmingham; Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, Alabama; VA Nebraska-Western Iowa Health Care System and University of Nebraska Medical Center, Omaha, Nebraska; Oregon Health Sciences University, Portland, Oregon, USA.|M.J. Burton, MD, Associate Professor, VA Medical Center, and Department of Medicine, Division of Infectious Diseases, University of Mississippi Medical Center; J.R. Curtis, MD, Professor, Birmingham VAMC, and Department of Medicine, Division of Rheumatology, University of Alabama at Birmingham; S. Yang, MS, Birmingham VAMC; L. Chen, PhD, Department of Medicine, Division of Rheumatology, University of Alabama at Birmingham; J.A. Singh, MBBS, MPH, Professor, Birmingham VAMC, and Department of Medicine, Division of Rheumatology, University of Alabama at Birmingham; T.R. Mikuls, MD, MSPH, Professor, VA Nebraska-Western Iowa Health Care System and University of Nebraska Medical Center; K.L. Winthrop, MD, Professor, Oregon Health Sciences University; J.W. Baddley, MD, Professor, Birmingham VAMC, and Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Curtis
authors.affiliation: From the Veterans Affairs (VA) Medical Center; Department of Medicine, Division of Infectious Diseases, University of Mississippi Medical Center, Jackson, Mississippi; Birmingham VA Medical Center (VAMC); Department of Medicine, Division of Rheumatology, University of Alabama at Birmingham; Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, Alabama; VA Nebraska-Western Iowa Health Care System and University of Nebraska Medical Center, Omaha, Nebraska; Oregon Health Sciences University, Portland, Oregon, USA.|M.J. Burton, MD, Associate Professor, VA Medical Center, and Department of Medicine, Division of Infectious Diseases, University of Mississippi Medical Center; J.R. Curtis, MD, Professor, Birmingham VAMC, and Department of Medicine, Division of Rheumatology, University of Alabama at Birmingham; S. Yang, MS, Birmingham VAMC; L. Chen, PhD, Department of Medicine, Division of Rheumatology, University of Alabama at Birmingham; J.A. Singh, MBBS, MPH, Professor, Birmingham VAMC, and Department of Medicine, Division of Rheumatology, University of Alabama at Birmingham; T.R. Mikuls, MD, MSPH, Professor, VA Nebraska-Western Iowa Health Care System and University of Nebraska Medical Center; K.L. Winthrop, MD, Professor, Oregon Health Sciences University; J.W. Baddley, MD, Professor, Birmingham VAMC, and Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham.
authors.forename: Shuo
authors.initials: S
authors.lastname: Yang
authors.affiliation: From the Veterans Affairs (VA) Medical Center; Department of Medicine, Division of Infectious Diseases, University of Mississippi Medical Center, Jackson, Mississippi; Birmingham VA Medical Center (VAMC); Department of Medicine, Division of Rheumatology, University of Alabama at Birmingham; Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, Alabama; VA Nebraska-Western Iowa Health Care System and University of Nebraska Medical Center, Omaha, Nebraska; Oregon Health Sciences University, Portland, Oregon, USA.|M.J. Burton, MD, Associate Professor, VA Medical Center, and Department of Medicine, Division of Infectious Diseases, University of Mississippi Medical Center; J.R. Curtis, MD, Professor, Birmingham VAMC, and Department of Medicine, Division of Rheumatology, University of Alabama at Birmingham; S. Yang, MS, Birmingham VAMC; L. Chen, PhD, Department of Medicine, Division of Rheumatology, University of Alabama at Birmingham; J.A. Singh, MBBS, MPH, Professor, Birmingham VAMC, and Department of Medicine, Division of Rheumatology, University of Alabama at Birmingham; T.R. Mikuls, MD, MSPH, Professor, VA Nebraska-Western Iowa Health Care System and University of Nebraska Medical Center; K.L. Winthrop, MD, Professor, Oregon Health Sciences University; J.W. Baddley, MD, Professor, Birmingham VAMC, and Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham.
authors.forename: Lang
authors.initials: L
authors.lastname: Chen
authors.affiliation: From the Veterans Affairs (VA) Medical Center; Department of Medicine, Division of Infectious Diseases, University of Mississippi Medical Center, Jackson, Mississippi; Birmingham VA Medical Center (VAMC); Department of Medicine, Division of Rheumatology, University of Alabama at Birmingham; Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, Alabama; VA Nebraska-Western Iowa Health Care System and University of Nebraska Medical Center, Omaha, Nebraska; Oregon Health Sciences University, Portland, Oregon, USA.|M.J. Burton, MD, Associate Professor, VA Medical Center, and Department of Medicine, Division of Infectious Diseases, University of Mississippi Medical Center; J.R. Curtis, MD, Professor, Birmingham VAMC, and Department of Medicine, Division of Rheumatology, University of Alabama at Birmingham; S. Yang, MS, Birmingham VAMC; L. Chen, PhD, Department of Medicine, Division of Rheumatology, University of Alabama at Birmingham; J.A. Singh, MBBS, MPH, Professor, Birmingham VAMC, and Department of Medicine, Division of Rheumatology, University of Alabama at Birmingham; T.R. Mikuls, MD, MSPH, Professor, VA Nebraska-Western Iowa Health Care System and University of Nebraska Medical Center; K.L. Winthrop, MD, Professor, Oregon Health Sciences University; J.W. Baddley, MD, Professor, Birmingham VAMC, and Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham.
authors.forename: Jasvinder A
authors.initials: JA
authors.lastname: Singh
authors.affiliation: From the Veterans Affairs (VA) Medical Center; Department of Medicine, Division of Infectious Diseases, University of Mississippi Medical Center, Jackson, Mississippi; Birmingham VA Medical Center (VAMC); Department of Medicine, Division of Rheumatology, University of Alabama at Birmingham; Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, Alabama; VA Nebraska-Western Iowa Health Care System and University of Nebraska Medical Center, Omaha, Nebraska; Oregon Health Sciences University, Portland, Oregon, USA.|M.J. Burton, MD, Associate Professor, VA Medical Center, and Department of Medicine, Division of Infectious Diseases, University of Mississippi Medical Center; J.R. Curtis, MD, Professor, Birmingham VAMC, and Department of Medicine, Division of Rheumatology, University of Alabama at Birmingham; S. Yang, MS, Birmingham VAMC; L. Chen, PhD, Department of Medicine, Division of Rheumatology, University of Alabama at Birmingham; J.A. Singh, MBBS, MPH, Professor, Birmingham VAMC, and Department of Medicine, Division of Rheumatology, University of Alabama at Birmingham; T.R. Mikuls, MD, MSPH, Professor, VA Nebraska-Western Iowa Health Care System and University of Nebraska Medical Center; K.L. Winthrop, MD, Professor, Oregon Health Sciences University; J.W. Baddley, MD, Professor, Birmingham VAMC, and Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham.
authors.forename: Ted R
authors.initials: TR
authors.lastname: Mikuls
authors.affiliation: From the Veterans Affairs (VA) Medical Center; Department of Medicine, Division of Infectious Diseases, University of Mississippi Medical Center, Jackson, Mississippi; Birmingham VA Medical Center (VAMC); Department of Medicine, Division of Rheumatology, University of Alabama at Birmingham; Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, Alabama; VA Nebraska-Western Iowa Health Care System and University of Nebraska Medical Center, Omaha, Nebraska; Oregon Health Sciences University, Portland, Oregon, USA.|M.J. Burton, MD, Associate Professor, VA Medical Center, and Department of Medicine, Division of Infectious Diseases, University of Mississippi Medical Center; J.R. Curtis, MD, Professor, Birmingham VAMC, and Department of Medicine, Division of Rheumatology, University of Alabama at Birmingham; S. Yang, MS, Birmingham VAMC; L. Chen, PhD, Department of Medicine, Division of Rheumatology, University of Alabama at Birmingham; J.A. Singh, MBBS, MPH, Professor, Birmingham VAMC, and Department of Medicine, Division of Rheumatology, University of Alabama at Birmingham; T.R. Mikuls, MD, MSPH, Professor, VA Nebraska-Western Iowa Health Care System and University of Nebraska Medical Center; K.L. Winthrop, MD, Professor, Oregon Health Sciences University; J.W. Baddley, MD, Professor, Birmingham VAMC, and Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham.
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Winthrop
authors.affiliation: From the Veterans Affairs (VA) Medical Center; Department of Medicine, Division of Infectious Diseases, University of Mississippi Medical Center, Jackson, Mississippi; Birmingham VA Medical Center (VAMC); Department of Medicine, Division of Rheumatology, University of Alabama at Birmingham; Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, Alabama; VA Nebraska-Western Iowa Health Care System and University of Nebraska Medical Center, Omaha, Nebraska; Oregon Health Sciences University, Portland, Oregon, USA.|M.J. Burton, MD, Associate Professor, VA Medical Center, and Department of Medicine, Division of Infectious Diseases, University of Mississippi Medical Center; J.R. Curtis, MD, Professor, Birmingham VAMC, and Department of Medicine, Division of Rheumatology, University of Alabama at Birmingham; S. Yang, MS, Birmingham VAMC; L. Chen, PhD, Department of Medicine, Division of Rheumatology, University of Alabama at Birmingham; J.A. Singh, MBBS, MPH, Professor, Birmingham VAMC, and Department of Medicine, Division of Rheumatology, University of Alabama at Birmingham; T.R. Mikuls, MD, MSPH, Professor, VA Nebraska-Western Iowa Health Care System and University of Nebraska Medical Center; K.L. Winthrop, MD, Professor, Oregon Health Sciences University; J.W. Baddley, MD, Professor, Birmingham VAMC, and Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham.
authors.forename: John W
authors.initials: JW
authors.lastname: Baddley
mesh_terms: D000368:Aged; D018501:Antirheumatic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy*; D001688:Biological Products / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006526:Hepatitis C / Q000150:complications*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D014728:Veterans
chemical_list: D018501:Antirheumatic Agents; D001688:Biological Products
keywords: ANTIRHEUMATIC AGENTS; CHRONIC HEPATITIS C; RHEUMATOID ARTHRITIS; VETERANS HEALTH