title: Safety of abatacept administered intravenously in treatment of rheumatoid arthritis: integrated analyses of up to 8 years of treatment from the abatacept clinical trial program.
abstract: OBJECTIVE
  To assess the overall safety, including rare events, of intravenous (IV) abatacept treatment in rheumatoid arthritis (RA).
  
  
  METHODS
  Data from 8 clinical trials of IV abatacept in RA were pooled. Safety events were assessed during the short-term (duration ≤ 12 months) and cumulative (short-term plus longterm extensions) abatacept treatment periods. Incidence rates per 100 patient-years were calculated. Standardized incidence ratios (SIR) for hospitalized infections and malignancies were compared with external RA cohorts and, for malignancies, with the US general population.
  
  
  RESULTS
  There were 3173 IV abatacept-treated patients with 2331 patient-years of exposure in the short-term periods, and 4149 IV abatacept-treated patients with 12,132 patient-years of exposure in the cumulative period. Incidence rates for serious infections were low and consistent over time (3.68 for abatacept vs 2.60 for placebo during the short-term, and 2.87 for abatacept during the cumulative period). Hospitalized infections were generally similar to external RA patient cohorts and were consistent over time. Incidence rates of malignancies were similar for abatacept- and placebo-treated patients during the short-term period (0.73 vs 0.59) and remained low during the abatacept cumulative period (0.73). SIR of some tissue-specific malignancies (e.g., colorectal and breast) in the cumulative period tended to be lower, while others (lymphoma and lung) tended to be higher, compared with the general population; however, incidence rates were comparable with RA cohorts. Autoimmune events were rare and infusion reactions uncommon.
  
  
  CONCLUSIONS
  Longterm safety of IV abatacept was consistent with the short-term, with no unexpected events and low incidence rates of serious infections, malignancies, and autoimmune events.
authors.affiliation: Brigham and Women's Hospital, Boston, MA, USA. mweinblatt@partners.org
authors.forename: Michael E
authors.initials: ME
authors.lastname: Weinblatt
authors.forename: Larry W
authors.initials: LW
authors.lastname: Moreland
authors.forename: Rene
authors.initials: R
authors.lastname: Westhovens
authors.forename: Roger B
authors.initials: RB
authors.lastname: Cohen
authors.forename: Sheila M
authors.initials: SM
authors.lastname: Kelly
authors.forename: Nader
authors.initials: N
authors.lastname: Khan
authors.forename: Ramesh
authors.initials: R
authors.lastname: Pappu
authors.forename: Ingrid
authors.initials: I
authors.lastname: Delaet
authors.forename: Allison
authors.initials: A
authors.lastname: Luo
authors.forename: Sheila
authors.initials: S
authors.lastname: Gujrathi
authors.forename: Marc C
authors.initials: MC
authors.lastname: Hochberg
mesh_terms: D000069594:Abatacept; D061605:Administration, Intravenous; D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D018796:Immunoconjugates; D000069594:Abatacept
keywords: RHEUMATOID ARTHRITIS; T CELLS; THERAPY; TUBERCULOSIS