Data from the Orencia Phase 3b AVERT and AMPLE trials to be presented at EULAR 2015

Bristol-Myers Squibb has announced that data from the Orencia Phase 3b AVERT and AMPLE trials will be presented in three separate posters during the European League Against Rheumatism Annual Congress (EULAR 2015).

These trials included early moderate to severe rheumatoid arthritis (RA) patients with active disease and markers of poor prognosis, such as ACPA (anti-citrullinated protein antibody) and rheumatoid factor (RF), which are both associated with more severe disease progression and joint damage. These data suggest a correlation between ACPA and treatment outcomes, and provide further data regarding the use of Orencia plus methotrexate (MTX) in these RA patients. In RA, activated T-cells in the immune response drive downstream inflammatory events that produce autoantibodies. Inhibiting T-cell activation in the immune response may help reduce autoantibody formation and levels.

AVERT demonstrates the potential impact of a biologic therapy on ACPA in the early stages of RA

One post hoc analysis of AVERT (Assessing Very Early Rheumatoid arthritis Treatment) found that in patients taking Orencia plus MTX, the proportion of patients who maintained DAS-defined remission following drug withdrawal was higher in patients with disease duration of three months or less, compared with patients with longer disease duration. Shorter disease duration was also associated with a faster onset of clinical response.

Exploratory data from the AVERT study assessed the impact of Orencia plus MTX on different types of ACPA and any association with clinical response. These data suggest Orencia in combination with MTX had greater clinical efficacy in patients who were IgM antibody type ACPA positive at the beginning of the study than in those who were negative for that antibody type, and in those who seroconverted over time than those who did not, suggesting the impact on ACPA is associated with a clinical benefit for RA patients.

“These data are among the first to demonstrate the potential impact of a biologic therapy on ACPA in the early stages of RA, which is characterised by high autoimmune activity and the presence of autoantibodies,” said T.W.J. Huizinga, M.D., PhD, Leiden University Medical Centre, Leiden Netherlands. “The findings further provide insight into the role of biological response markers in helping define the disease and manage therapy.”

AVERT and AMPLE studies yield promising insights into RA disease progression

Additionally, an exploratory analysis of AMPLE (Abatacept Versus Adalimumab Comparison in Biologic-Naïve rheumatoid arthritis (RA) Subjects With Background Methotrexate) suggests higher serum ACPA levels at baseline correlated with a better clinical response from Orencia plus MTX compared to adalimumab plus MTX. When patients were divided into quartiles based on baseline ACPA titer, significant differences in response were observed between patients in the highest titer quartile (Q4) versus Q1–3 for DAS28 (CRP) and HAQ-DI in the Orencia treated arm, while, Q4 versus Q1–3 treatment differences were not significant with adalimumab.

“These analyses yield promising insights into RA disease progression,” said Douglas Manion, M.D., Head of Specialty Development, Bristol-Myers Squibb. “With further investigation, we can provide additional understanding into the use of Orencia plus methotrexate in patients with early, active, moderate to severe RA.”