New data reinforces improved and durable responses of Orencia in moderate-to-severe early rheumatoid arthritis patients with autoantibodies linked to more severe disease. – BMS

Bristol Myers Squibb announced results from the open-label switch period of Early AMPLE, a Phase IV exploratory biomarker study assessing the differences by which Orencia (abatacept) and another treatment, adalimumab, interfere with disease progression in moderate-to-severe early rheumatoid arthritis (RA) patients who tested positive (seropositive) for certain autoantibodies.

Findings of the open-label switch period showed that early seropositive RA patients treated with Orencia demonstrated substantial clinical improvements at week 48, sustaining the level of responses achieved at week 24 compared to adalimumab. In seropositive patients switching from adalimumab to Orencia, the efficacy responses generally increased over the open-label period to week 48. These results are featured in a poster presentation at the European E-Congress of Rheumatology (EULAR) 2020.

The Early AMPLE study included early (less than 12 months from symptom onset) moderate-to-severe RA patients who had never been treated with a biologic medication and who were seropositive for autoantibodies called anti-citrullinated protein antibody (ACPA) and rheumatoid factor (RF). These patients are considered to have more highly active, progressive RA and a poor disease prognosis.

Findings showed that among the 76 seropositive RA patients who entered the open-label switch period: 1.The efficacy responses observed at 24 weeks with Orencia were sustained at week 48 in the patients who continued on Orencia. At week 48, ACR 20/50/70 responses with Orencia in the non-switch arm were 78, 63 and 50, respectively. At week 24, ACR 20/50/70 responses with Orencia were 83, 73 and 50, respectively; ACR 20/50/70 scores for adalimumab at week 24 were 63, 45 and 30, respectively. 2. In the patients who switched from adalimumab to Orencia, while the trial was not powered to show superiority or non-inferiority, the efficacy responses generally increased over the open-label period through week 48. ACR 20/50/70 scores for patients who switched from adalimumab to Orencia were 75, 63 and 38, respectively, at week 48. 3. Overall, patients with a well-known genetic marker of RA prognosis, called the “Shared Epitope” (SE), who continued on Orencia achieved numerically higher responses than the broader seropositive patient population at week 48, indicating the potential importance of SE as a predictor of response to Orencia. ACR 20/50/70 responses were 77, 67 and 53, respectively, for SE+ patients continuing on Orencia. 4. The overall safety profile of Orencia was consistent with prior studies, with no new safety signals identified.

The HLA-DRB1 allele, which codes for the Shared Epitope, provides instructions for making a protein that plays a key role in helping the immune system distinguish one’s own proteins from those of harmful invaders, such as bacteria and viruses. Shared Epitope has been shown to be strongly associated with RA, and is thought to be involved with the overactivation of immune cells, called T cells, that characterizes RA. Shared Epitope is present in 70-80 percent of RA patients positive for ACPA..

Following the encouraging results of this study, Bristol Myers Squibb has initiated a clinical trial program to further explore the potential for improved efficacy of Orencia in seropositive RA, and the additional impact that Shared Epitope may have on this, through new head-to-head studies versus a TNF inhibitor and a JAK inhibitor