Rheumatoid Arthritis Drug Combination May Slow Disease Progression

First-line therapy with abatacept in combination with methotrexate achieved significantly higher rates of stringent measures of remission in patients with early rheumatoid arthritis.

First-line therapy with abatacept in combination with methotrexate achieved significantly higher rates of stringent measures of remission in patients with early rheumatoid arthritis.

Results from several new sub-analyses of a phase 3 trial for a rheumatoid arthritis (RA) treatment showed promising results in achieving higher rates of remission for adults with early stage disease.

Abatacept (Orencia), manufactured by Bristol-Myers Squibb, is currently indicated for adults with moderate to severe RA. Treatment with abatacept in combination with methotrexate (MTX) in biologic and MTX-naïve citrullinated protein (CCP)-positive early to severe RA patients exhibited significantly higher rates for stringent measures of remission.

Results from the AVERT (Assessing Very Early Rheumatoid arthritis Treatment) trial showed 37% of patients achieving Boolean-defined remission and 42% of patients achieving CDAI- and SDAI-defined remission at 12 months compared with patients on MTX alone, which achieved results of 22.4%, 27.6%, and 25%, respectively.

“Important results were seen in CCP-positive patients,” said T.W.J. Huizinga, MD, PhD, in a press release. “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.”

Results from the trial were presented this week at the American College of Rheumatology (ACR) 2014 annual meeting.

Researchers also assessed the development of anti-CCP antibodies in patients with early rapidly progressing RA by measuring isotypes and the number of epitopes recognized after treatment with abatacept plus MTX, abatacept alone, or MTX alone. The results indicated abatacept with MTX numerically decreased the concentrations of all CCP isotypes and the average number of epitopes recognized over 1 year of treatment more than abatacept alone or MTX alone.

Over the course of a year, 6.7%, 12.1%, and 7.8% of patients on abatacept plus MTX, abatacept alone, and MTX alone, respectively, experienced a serious adverse event. The adverse events led to 1.7%, 4.3% and 2.6% of patients, respectively discontinuing the treatment.

There were serious infections observed in 0.8% of patients in the combination arm and 3.4% in the abatacept monotherapy arm. None of the patients in the MTX alone arm experienced a serious infection.

Significantly more patients treated with abatacept plus MTX achieved the stringent clinical endpoint of Boolean-defined remission after 1 year, with 37% in the abatacept plus MTX cohort, compared with 26.7% in the abatacept monotherapy cohort, and 22.4% treated with MTX alone.

There were also consistently higher remission rates in the abatacept plus MTX group when compared with MTX alone or abatacept alone. These included CDAI remission (42% abatacept plus MTX; 31% abatacept alone; 27.6% MTX alone) and SDAI remission (42% abatacept plus MTX; 29.3% abatacept alone; 25% MTX alone).

“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,” Bristol-Myers Squibb Head of Specialty Development Douglas Manion, MD, said in a press release. “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.”