Comparative Safety of Infliximaband Etanercept on the Risk of Serious Infections TOH


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Comparative Safety of Infliximaband Etanercept on the Risk of Serious Infections TOH

  1. 1. Comparative safety of infliximab and etanercept on the risk of serious infection Does the association vary by patient characteristics?Darren Toh, ScDLingling Li, PhDLeslie R. Harrold, MD, MPHElizabeth A. Bayliss, MD, MSPHJeffrey R. Curtis, MD, MS, MPHLiyan Liu, MSLang Chen, PhDCarlos G. Grijalva, MD, MPHLisa J. Herrinton, PhD
  2. 2. Background• Infliximab, a chimeric monoclonal anti-TNF antibody, has been found to increase the risk of serious infections compared to etanercept (a TNF receptor fusion protein)• It is unclear whether the risk varies by patient characteristics 2
  3. 3. Objective• To assess if the relative risk of serious infections comparing infliximab and etanercept varies by five patient characteristics (age, sex, race/ethnicity, and body mass index, smoking status) 3
  4. 4. Study cohort 4
  5. 5. Exposure• Infliximab: Administered through infusion; each infusion covers 56 days• Etanercept: Self-administered via injection; each injection covers 7 days and each dispensing containing 4 injections 5
  6. 6. Outcome • Serious infections, defined as infections requiring hospitalization or opportunistic infections • Used previously validated algorithms to identify serious infection cases (PPV of ≥80%)Grijalva et al, JAMA 2011;306: 2331-2339 6
  7. 7. Potential confounders & effect modifiers• Age; sex; race/ethnicity; body mass index; smoking status• Type of insurance; proportion of household below the poverty line in the census block in which the patient lived• Charlson comorbidity score; diagnosis of rheumatoid arthritis, psoriatic arthritis, psoriasis, ankylosing spondylitis, diabetes, or COPD• Use of methotrexate, hydroxychloroquine, leflunomide, sulfasalazine, NSAIDs, opioids, corticosteroids, or antibiotics• Number of inpatient visits, outpatient visits, and unique medications dispensed 7
  8. 8. Statistical analysis• Calculated the incidence rate and 95% CI• Propensity score stratified (by quintiles) Cox model to adjust for potential confounders • HRs and 95% CIs comparing infliximab vs. etanercept • An “intention-to-treat” analysis • Follow-up started from treatment initiation to the earliest occurrence of the outcome, death, disenrollment, 12/31/2007, or 365 days after treatment initiation • 0-3, 0-6, and 0-12 months after treatment initiation 8
  9. 9. Statistical analysis (cont)• Stratified the analysis by • Age: <65 vs. ≥65 years • Sex: male vs. female • Race/ethnicity: Non-Hispanic White, African-American, Hispanic, Asian American, Native American, and other or unknown • BMI: <25 vs. ≥25 kg/m2 • Smoking status: non, past, and current smoker• Likelihood ratio test to assess effect modification 9
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  15. 15. Discussion• The relation between infliximab and serious infections may be modified by age • Increased risk observed only among patients <65 years • No increased risk among patients ≥65 years • Ceiling effect?• No strong evidence to suggest that the effect is modified by other patient characteristics examined• Need to be confirmed or refuted by other studies 15
  16. 16. Discussion (cont)• Limitations • Residual confounding by disease severity • Residual confounding by non-specific propensity score • ITT analysis may be biased due to exposure misclassification • 48% BMI and 66% smoking determined by ICD-9 codes 16
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