Rheumatoid Arthritis Treatments - CTLA4Ig
OP0015 ABATACEPT SUSTAINS INHIBITION OF RADIOGRAPHIC PROGRESSION OVER 2 YEARS IN RHEUMATOID ARTHRITIS (RA) PATIENTS WITH AN INADEQUATE RESPONSE TO METHOTREXATE (MTX): RESULTS FROM THE LONG-TERM EXTENSION (LTE) OF THE AIM TRIAL
H.K. Genant, C. Peterfy, R. Westhovens, J.P. Becker, R. Aranda, J. Teng, J.M. Kremer
In addition to improving clinical signs and symptoms of rheumatoid arthritis (RA), abatacept (Orencia) has been shown to be effective at slowing radiographic progression of RA in studies extending to 12 months. Here, Genant et al compare radiographic progression in methotrexate non-responders treated with the combination of abatacept and methotrexate in the open-label extension phase of the AIM (Abatacept in Inadequate responders to Methotrexate) trial.
Methods During the 12 month double-blind portion of the trial, RA patients with an inadequate response to methotrexate were randomized in a 2:1 proportion to receive either abatacept, dosed at approximately 10mg/kg, or placebo infused every 4 weeks in addition to their background dose of weekly methotrexate. After completion of the 12 month double blinded phase, all subjects remaining in the trial were eligible to receive abatacept in an open-label fashion.
Plain radiography of the hands and feet was obtained at baseline, and at 12 and 24 months. Paired radiographs were scored by independent radiologists blinded to treatment allocation and sequence. The Genant modification of the Sharp scoring method was utilized with the change in erosion score over 24 months as the primary outcome measure of this analysis. Secondary outcomes included change in joint space narrowing and change in total score. For subjects withdrawing from the study before 24 months, linear extrapolation was used to approximate radiographic progression at 24 months.
Results: 652 subjects were enrolled, of whom 539 entered the open label phase. 467 subjects continued in the study to 24 months. Patient characteristics were typical of clinical trials of RA therapeutics and were balanced according to group allocation.
For the change in erosion score at 12 months, subjects receiving abatacept + background methotrexate progressed a mean of 0.62 + 1.82 units compared to 1.44 + 3.11 units in the group that received placebo + background methotrexate. At 24 months, after 12 months of open label extension with both groups having received abatacept + background methotrexate, subjects who had received abatacept for the entire 24 month study period demonstrated a mean progression from baseline in erosion scores of 0.84 + 2.05 units compared to 1.69 + 3.44 units in the group that received placebo for the first 12 months. The difference in erosion scores between the two groups during the second year was not significantly different (0.21 + 1.06 vs. 0.25 + 1.72, respectively). Similar relationships were observed for joint space narrowing and total score. Fifty-six percent of abatacept treated subjects were classified as radiographic non-progressors at year one. By year two, 50% of abatacept treated subjects were classified as non-progressors.
Conclusions: RA treatment with abatacept over two years was associated with sustained inhibition of radiographic progression.
Editorial Comment: These are important results in establishing that early inhibition of radiographic progression can be sustainable over an extended period. Obviously, integrating data involving both a double-blind and an open-label treatment phase make the interpretation of these results somewhat challenging in context, particularly here where information on subjects who did not continue in the protocol are not detailed. In addition, while radiographic progression is numerically more rapid in the non-abatacept treated subjects, no statistical comparisons were provided. Indeed, the absolute values for progression appear rather low in both groups. Care should be taken when comparing the magnitude of radiographic inhibition to similar studies of TNF inhibitors, as a different scoring system is employed here. To date, no studies have been performed comparing the potential for inhibition of radiographic progression in abatacept vs. TNF-inhibitor treated patients, nor have there been studies in early RA or methotrexate nave RA patients.