The results of several new sub-analyses of the phase IIIb AVERT ( Assessing Very Early Rheumatoid arthritis Treatment ) trial that investigated the use of Abatacept ( Orencia ) plus Methotrexate ( MTX ) in biologic and MTX-naïve citrullinated protein (CCP)-positive early moderate to severe rheumatoid arthritis patients, were presented at the American College of Rheumatology ( ACR ) 2014 annual meeting.
Orencia is currently indicated in adults for moderate to severe rheumatoid arthritis. Orencia should not be administered with tumor necrosis factor antagonists and should not be used with other biologic rheumatoid arthritis drugs.
One of the analyses looked at anti-CCP antibodies, which are a marker of rheumatoid arthritis and may contribute to disease progression. The analysis assessed the development of anti-CCP antibodies in patients with early rapidly progressing rheumatoid arthritis 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 Abatacept plus Methotrexate, Abatacept alone, or Methotrexate alone.
Abatacept plus Methotrexate numerically reduced the concentrations of all CCP isotypes and the average number of epitopes recognized over one year of treatment more than Abatacept alone or Methotrexate alone.
Over 12 months of treatment, 6.7%, 12.1%, and 7.8% of patients on Abatacept plus Methotrexate, Abatacept alone, and Methotrexate alone, respectively, experienced a serious adverse event and 1.7%, 4.3% and 2.6% led to discontinuation.
Serious infections were observed in 0.8% of patients in the combination arm and 3.4% in the Abatacept monotherapy arm.
None of the patients in the Methotrexate alone arm experienced a serious infection. Malignancies were reported in 0.8%, 1.7%, and 0% of patients in the Abatacept plus Methotrexate, Abatacept, and Methotrexate arms, respectively.
Additionally at ACR, investigators presented 12-month efficacy data from AVERT, including new results assessing the effect of Abatacept on more clinically stringent remission criteria than DAS-defined ( DAS28 CRP less than 2.6 ) remission, as well as new MRI data.
Significantly more patients on Abatacept plus Methotrexate achieved the stringent clinical endpoint of Boolean-defined remission at 12 months ( 37% Abatacept plus Methotrexate; 26.7% Abatacept alone; 22.4% Methotrexate alone; P less than 0.05 ).
Higher remission rates as compared to Methotrexate or Abatacept alone were consistent across other clinically stringent measures, including CDAI remission ( 42% Abatacept plus Methotrexate; 31% Abatacept alone; 27.6% Methotrexate alone; P less than 0.05 ) and SDAI remission ( 42% Abatacept plus Methotrexate; 29.3% Abatacept alone; 25% Methotrexate alone; P less than 0.05 ).
A small but significantly higher number of patients treated with Abatacept plus Methotrexate 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 less than 2.4 ( 13% Abatacept plus Methotrexate; vs. 3.5% Methotrexate alone; P=0.002 ).
Sustained improvements on MRI endpoints were also observed at six months after stopping combination therapy with Abatacept plus Methotrexate vs. Methotrexate 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 Abatacept plus Methotrexate vs. -0.49 for Methotrexate alone; -2.03 for Abatacept plus Methotrexate vs. 0.34 for Methotrexate alone in total osteitis score; and 0.13 for Abatacept plus Methotrexate vs. 2.00 for Methotrexate alone in total erosion score ( p less than 0.05 for all three measures ).
Abatacept plus Methotrexate has improved patient-reported outcomes for fatigue, pain, physical functioning and participation in daily activities compared to Methotrexate.
At 12 months, the Abatacept plus Methotrexate treatment arm reported a significant improvement in fatigue ( -34.9 ) vs. Methotrexate alone ( -26.7; P less than 0.05 ); and in health-related quality of life score, 13.9 for Abatacept plus Methotrexate vs. 10.9 for Methotrexate alone; ( P less than 0.05 ). ( Xagena )
Source: Bristol-Myers Squibb ( BMS ), 2014