Analyses from Phase IIIb Study provide additional data in earlier use of Orencia (abatacept) plus Methotrexate (MTX)

Bristol-Myers Squibb Company (NYSE:BMY) today announced results of several new sub-analyses of the Phase IIIb AVERT (Assessing Very Early Rheumatoid arthritis Treatment) trial that investigated the use of Orencia plus methotrexate (MTX) in biologic and MTX-naïve citrullinated protein (CCP)-positive early moderate to severe rheumatoid arthritis (RA) patients. These data were presented this week at the American College of Rheumatology (ACR) 2014 annual meeting.

Orencia is currently indicated in adults for moderate to severe RA. Orencia should not be administered with tumor necrosis factor antagonists and should not be used with other biologic RA drugs.

One of the analyses looked at anti-CCP antibodies, which are a marker of RA and may contribute to disease progression. The analysis assessed the development of anti-CCP antibodies in patients with early rapidly progressing RA by measuring isotypes (related antibody classes) and the number of epitopes (a specific area of an antigen to which an antibody binds) recognized after treatment with Orencia plus MTX, Orencia alone, or MTX alone. Results demonstrated Orencia plus MTX numerically reduced the concentrations of all CCP isotypes and the average number of epitopes recognized over one year of treatment more than Orencia alone or MTX alone.

“Important results were seen in CCP-positive patients,” said T.W.J. Huizinga, MD, PhD, Leiden University Medical Center, Leiden Netherlands. “The results of our analysis demonstrate that patients who start treatment with a combination of Orencia plus methotrexate in early rheumatoid arthritis may potentially slow disease progression.”

Over 12 months of treatment, 6.7 percent, 12.1 percent, and 7.8 percent of patients on Orencia plus MTX, Orencia alone, and MTX alone, respectively, experienced a serious adverse event and 1.7 percent, 4.3 percent and 2.6 percent led to discontinuation. Serious infections were observed in 0.8 percent of patients in the combination arm and 3.4 percent in the Orencia monotherapy arm. None of the patients in the MTX alone arm experienced a serious infection. Malignancies were reported in 0.8 percent, 1.7 percent, and 0 percent of patients in the Orencia + MTX, Orencia, and MTX arms, respectively.

Additional AVERT Sub-Analyses Findings

Additionally at ACR, investigators presented 12-month efficacy data from AVERT, including new results assessing the effect of Orencia on more clinically stringent remission criteria than DAS-defined (DAS28 CRP <2.6) remission, as well as new MRI data.

Significantly more patients on Orencia plus MTX achieved the stringent clinical endpoint of Boolean-defined remission at 12 months (37 percent Orencia plus MTX; 26.7 percent Orencia alone; 22.4 percent MTX alone; P<0.05). Higher remission rates as compared to MTX or Orencia alone were consistent across other clinically stringent measures, including CDAI remission (42 percent Orencia plus MTX; 31 percent Orencia alone; 27.6 percent MTX alone; P<0.05) and SDAI remission (42 percent Orencia plus MTX; 29.3 percent Orencia alone; 25 percent MTX alone; P<0.05). A small but significantly higher number of patients treated with Orencia plus MTX were able to maintain drug-free remission up to month 18 and six months after drug withdrawal, according to the remission threshold of DAS28-CRP <2.4 (13 percent Orencia plus MTX; vs. 3.5 percent MTX alone; P=0.002).

Sustained improvements on MRI endpoints were also observed at six months after stopping combination therapy with Orencia plus MTX vs. MTX alone, including improved measurements of both joint inflammation and joint erosion. At 18 months of this post-hoc analysis, the adjusted mean change from baseline in total synovitis score was -1.34 for Orencia plus MTX vs. -0.49 for MTX alone; -2.03 for Orencia plus MTX vs. 0.34 for MTX alone in total osteitis score; and 0.13 for Orencia plus MTX vs. 2.00 for MTX alone in total erosion score (p<0.05 for all three measures).

“The new AVERT findings presented at ACR reinforce Bristol-Myers Squibb’s commitment to understanding the disease pathology of RA and the results associated with earlier treatment with a combination of Orencia plus methotrexate,” said Douglas Manion, M.D., head of Specialty Development, Bristol-Myers Squibb. “Collectively, the efficacy, safety and real-world data presented at ACR will provide clinicians with valuable insights into treatment response and outcomes in patients with early rheumatoid arthritis.”

Patient-Reported Outcomes

Orencia plus MTX improved patient-reported outcomes for fatigue, pain, physical functioning and participation in daily activities compared to MTX. At 12 months, the Orencia plus MTX treatment arm reported a significant improvement in fatigue (-34.9) vs. MTX alone (-26.7; P<0.05); and in health-related quality of life score, 13.9 for Orencia plus MTX vs. 10.9 for MTX alone; (P<0.05). Recent EULAR recommendations reinforce the need to assess a treatment’s impact on the patient’s daily activities and overall quality of life.