title: Use of a disease risk score to compare serious infections associated with anti-tumor necrosis factor therapy among high- versus lower-risk rheumatoid arthritis patients.
abstract: OBJECTIVE
  To evaluate whether rates of serious infection with anti-tumor necrosis factor (anti-TNF) therapy in rheumatoid arthritis (RA) patients differ in magnitude by specific drugs and patient characteristics.
  
  
  METHODS
  Among new nonbiologic disease-modifying antirheumatic drug users enrolled in Medicare and Medicaid or a large US commercial health plan, we created and validated a person-specific infection risk score based on age, demographics, insurance type, glucocorticoid dose, and comorbidities to identify patients at high risk for hospitalized infections. We then applied this risk score to new users of infliximab, etanercept, and adalimumab and compared the observed 1-year rates of infection to one another and to the predicted infection risk score estimated in the absence of anti-TNF exposure.
  
  
  RESULTS
  Among 11,657 RA patients initiating anti-TNF therapy, the observed 1-year rate of infection was 14.2 infections per 100 person-years in older patients (age ≥65 years) and 4.8 in younger patients (age <65 years). There was a relatively constant rate difference of ~1-4 infections per 100 person-years associated with anti-TNF therapy across the range of the infection risk score. Infliximab had a significantly greater adjusted rate of infection compared to etanercept and adalimumab in both high- and lower-risk RA patients.
  
  
  CONCLUSIONS
  The rate of serious infections for anti-TNF agents was incrementally increased by a fixed absolute difference irrespective of age, comorbidities, and other factors that contributed to infections. Older patients and those with high comorbidity burdens should be reassured that the magnitude of their incremental risk with anti-TNF agents is not greater than for lower-risk patients.
authors: University of Alabama at Birmingham, Birmingham, AL, USA. jcurtis@uab.edu
authors: Jeffrey R
authors: JR
authors: Curtis
authors: Fenglong
authors: F
authors: Xie
authors: Lang
authors: L
authors: Chen
authors: Paul
authors: P
authors: Muntner
authors: Carlos G
authors: CG
authors: Grijalva
authors: Claire
authors: C
authors: Spettell
authors: Joaquim
authors: J
authors: Fernandes
authors: Raechele M
authors: RM
authors: McMahan
authors: John W
authors: JW
authors: Baddley
authors: Kenneth G
authors: KG
authors: Saag
authors: Timothy
authors: T
authors: Beukelman
authors: Elizabeth
authors: E
authors: Delzell
mesh_terms: D000068879:Adalimumab; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D000068800:Etanercept; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects / Q000627:therapeutic use; D007239:Infections / Q000139:chemically induced*; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D012306:Risk; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept