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

• 1. Comparative safety of infliximab and etanercept on the risk of serious infectionDoes the association vary by patientcharacteristics?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. Background Infliximab, a chimeric monoclonal anti-TNF antibody,has been found to increase the risk of seriousinfections compared to etanercept (a TNF receptorfusion protein) It is unclear whether the risk varies by patientcharacteristics 2 3. Objective To assess if the relative risk of serious infectionscomparing infliximab and etanercept varies by fivepatient characteristics (age, sex, race/ethnicity, andbody mass index, smoking status) 3 4. Study cohort 4 5. Exposure Infliximab: Administered through infusion; eachinfusion covers 56 days Etanercept: Self-administered via injection; eachinjection covers 7 days and each dispensingcontaining 4 injections5 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. Potential confounders & effect modifiers Age; sex; race/ethnicity; body mass index; smoking status Type of insurance; proportion of household below the povertyline in the census block in which the patient lived Charlson comorbidity score; diagnosis of rheumatoid arthritis,psoriatic arthritis, psoriasis, ankylosing spondylitis, diabetes, orCOPD Use of methotrexate, hydroxychloroquine, leflunomide,sulfasalazine, NSAIDs, opioids, corticosteroids, or antibiotics Number of inpatient visits, outpatient visits, and uniquemedications dispensed 7 8. Statistical analysis Calculated the incidence rate and 95% CI Propensity score stratified (by quintiles) Cox model toadjust 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. Statistical analysis (cont) Stratified the analysis by Age: