title: Opioid Analgesics and the Risk of Serious Infections Among Patients With Rheumatoid Arthritis: A Self-Controlled Case Series Study.
abstract: OBJECTIVE
  Animal studies and in vitro human studies suggest that certain opioid analgesics impair crucial immune functions. This study was undertaken to determine whether opioid use is associated with increased risk of serious infection in patients with rheumatoid arthritis (RA).
  
  
  METHODS
  We conducted a self-controlled case series analysis on a retrospective cohort of 13,796 patients with RA enrolled in Tennessee Medicaid in 1995-2009. Within-person comparisons of the risk of hospitalization for serious infection during periods of opioid use versus non-use were performed using conditional Poisson regression. Fixed confounders were accounted for by design; time-varying confounders included age and use of disease-modifying antirheumatic drugs, glucocorticoids, and proton-pump inhibitors. In additional analyses, risks associated with new opioid use, use of opioids known to have immunosuppressive properties, use of long-acting opioids, and different opioid dosages were assessed. Sensitivity analyses were performed to account for potential protopathic bias and confounding by indication.
  
  
  RESULTS
  Among 1,790 patients with RA who had at least 1 hospitalization for serious infection, the adjusted incidence rate of serious infection was higher during periods of current opioid use compared to non-use, with an incidence rate ratio (IRR) of 1.39 (95% confidence interval [95% CI] 1.19-1.62). The incidence rate was also higher during periods of long-acting opioid use, immunosuppressive opioid use, and new opioid use compared to non-use (IRR 2.01 [95% CI 1.52-2.66], IRR 1.72 [95% CI 1.33-2.23], and IRR 2.38 [95% CI 1.65-3.42], respectively). Results of sensitivity analyses were consistent with the main findings.
  
  
  CONCLUSIONS
  In within-person comparisons of patients with RA, opioid use was associated with an increased risk of hospitalization for serious infection.
authors.affiliation: Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Wiese
authors.affiliation: Vanderbilt University Medical Center, Mid-South Geriatric Research Education and Clinical Center, VA Tennessee Valley Health Care System, Nashville Campus, Nashville, Tennessee.
authors.forename: Marie R
authors.initials: MR
authors.lastname: Griffin
authors.affiliation: Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: C Michael
authors.initials: CM
authors.lastname: Stein
authors.affiliation: Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Edward F
authors.initials: EF
authors.lastname: Mitchel
authors.affiliation: Vanderbilt University Medical Center, Mid-South Geriatric Research Education and Clinical Center, VA Tennessee Valley Health Care System, Nashville Campus, Nashville, Tennessee.
authors.forename: Carlos G
authors.initials: CG
authors.lastname: Grijalva
mesh_terms: D000328:Adult; D000367:Age Factors; D000701:Analgesics, Opioid / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000453:epidemiology; D003061:Codeine / Q000627:therapeutic use; D015331:Cohort Studies; D003692:Delayed-Action Preparations; D011431:Dextropropoxyphene / Q000627:therapeutic use; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D006853:Hydrocodone / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015994:Incidence; D007239:Infections / Q000453:epidemiology*; D008484:Medicaid; D008875:Middle Aged; D009020:Morphine / Q000627:therapeutic use; D010098:Oxycodone / Q000627:therapeutic use; D012189:Retrospective Studies; D012307:Risk Factors; D013714:Tennessee / Q000453:epidemiology; D014481:United States
chemical_list: D000701:Analgesics, Opioid; D018501:Antirheumatic Agents; D003692:Delayed-Action Preparations; D007166:Immunosuppressive Agents; D006853:Hydrocodone; D009020:Morphine; D010098:Oxycodone; D011431:Dextropropoxyphene; D003061:Codeine