title: Clinical and patient-reported outcomes in clinical trials of abatacept in the treatment of rheumatoid arthritis.
abstract: BACKGROUND
  Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic joint inflammation, which if left untreated leads to progressive disability and joint destruction. A combination of antiinflammatory agents, steroids, disease-modifying antirheumatic drugs, and biological agents are used to treat RA. Beyond the use of conventional measures of disease activity, such as American College of Rheumatology (ACR) response rates, the importance of patient-reported outcomes (PROs) in assessing therapeutic benefits is gaining increasing emphasis in clinical trials of RA and other chronic illnesses. Clinical trials testing new RA therapeutics generally include health-related quality of life (HRQoL) measures and assessments of function and disability. Abatacept, a costimulation modulator that selectively targets the activation of T cells and downregulates the immune response, has been approved by the US Food and Drug Administration for the treatment of RA, with or without methotrexate.
  
  
  OBJECTIVE
  The aim of this review was to summarize the clinical outcomes and PROs in published trials of abatacept.
  
  
  METHODS
  A literature search was performed using the MEDLINE, EMBASE, and BIOSIS databases (restricted to articles posted between January 2000 and September 2007) with the search terms CTLA-4Ig, abatacept, and Orencia to identify published trials of abatacept. Primary clinical trial publications in patients with RA were selected. The ACR response and PROs data presented in the identified publications are summarized in this review.
  
  
  RESULTS
  Our search identified 6 studies that met our selection criteria, which included 1 Phase IIa study, 2 Phase IIb studies, and 3 Phase III studies. The Phase IIa study found that abatacept was more effective than placebo and that physical function improved in treated patients compared with placebo. The 2 Phase IIb studies in 339 patients with RA previously treated with methotrexate found statistically significant improvements in HRQoL with abatacept at 6 months and 1 year. Similar findings were noted in the published Phase III trials. Across clinical trials, abatacept has been associated with clinically meaningful and statistically significant improvements in conventional measures of disease activity, HRQoL, and physical function.
  
  
  CONCLUSIONS
  These 6 published trials found that abatacept was associated with significant improvements in both conventional measures of disease activity and PROs. Continued assessment of these outcomes will be required to further support the findings of the Phase II and III abatacept clinical trial literature reviewed here.
authors.affiliation: Division of Rheumatology, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts 02115, USA. emassarotti@partners.org
authors.forename: Elena M
authors.initials: EM
authors.lastname: Massarotti
mesh_terms: D000069594:Abatacept; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data*; D006304:Health Status; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use*; D010865:Pilot Projects; D011788:Quality of Life; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D018796:Immunoconjugates; D000069594:Abatacept