title: Infections requiring hospitalization in the abatacept clinical development program: an epidemiological assessment.
abstract: BACKGROUND
  Patients with rheumatoid arthritis (RA) have an increased risk of infection and this risk appears to be higher with anti-TNF (tumor necrosis factor) agents. We pooled data from the cumulative abatacept RA clinical development program, both double-blind and open-label periods, to estimate the incidence rates (IRs) of infections requiring hospitalization including pneumonia and opportunistic infections, in comparison with RA patients treated with non-biologic disease-modifying antirheumatic drugs (DMARDs) from several reference cohorts.
  
  
  METHODS
  Infections reported in seven abatacept clinical trials of RA patients (double-blind and open-label periods) were tabulated. Comparisons were made between the observed IRs in abatacept-treated patients and those in over 133,000 patients exposed to non-biologic DMARDs in six reference RA cohorts. Age- and sex-adjusted IRs of infections requiring hospitalization, including pneumonia (most frequent hospital infection), were used to estimate the expected IRs with abatacept by the method of indirect adjustment. Standardized incidence ratios (SIR) and 95% CI were calculated comparing incidence in the cumulative abatacept experience with incidence in each RA cohort.
  
  
  RESULTS
  A total of 1,955 (double-blind period) and 4,134 (double-blind + open-label periods with a cumulative exposure of 8,392 person-years) abatacept-treated RA patients were analyzed. Observed IRs for infections requiring hospitalization during the double-blind period were 3.05 per 100-patient years for abatacept-treated patients and 2.15 per 100 patient years for placebo. In the cumulative population, observed IR for infections requiring hospitalization was 2.72 per 100-patient years. Rates for abatacept were similar to expected IRs based on other RA non-biologic DMARD cohorts.
  
  
  CONCLUSIONS
  IRs of infections requiring hospitalization and pneumonia in abatacept trials are consistent with expected IRs based on reference RA DMARD cohorts. RA patients are at higher risk of infection compared with the general population, making the RA DMARD cohorts an appropriate reference group. The safety of abatacept, including incidence of infections requiring hospitalization, will continue to be monitored in a post-marketing surveillance program.
authors.affiliation: Global Health Economics and Outcomes Research, Bristol-Myers Squibb, Route 206 and Province Line Roads, Lawrenceville, NJ 08540, USA. teresa.simon@bms.com
authors.forename: Teresa A
authors.initials: TA
authors.lastname: Simon
authors.forename: Johan
authors.initials: J
authors.lastname: Askling
authors.forename: Diane
authors.initials: D
authors.lastname: Lacaille
authors.forename: Jarrod
authors.initials: J
authors.lastname: Franklin
authors.forename: Frederick
authors.initials: F
authors.lastname: Wolfe
authors.forename: Allison
authors.initials: A
authors.lastname: Covucci
authors.forename: Samy
authors.initials: S
authors.lastname: Suissa
authors.forename: Marc C
authors.initials: MC
authors.lastname: Hochberg
mesh_terms: D000069594:Abatacept; D000293:Adolescent; D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000453:epidemiology*; D015897:Comorbidity; D004311:Double-Blind Method; D005060:Europe / Q000453:epidemiology; D005260:Female; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D018796:Immunoconjugates / Q000009:adverse effects*; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009656:North America / Q000453:epidemiology; D009894:Opportunistic Infections / Q000453:epidemiology* / Q000209:etiology; D016032:Randomized Controlled Trials as Topic; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D055815:Young Adult
chemical_list: D018501:Antirheumatic Agents; D018796:Immunoconjugates; D014409:Tumor Necrosis Factor-alpha; D000069594:Abatacept
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