New RA drug effective in phase 3 trials

Patients treated with abatacept had similar rates of adverse events to patients receiving placebo.

VIENNA, Austria — A new drug may be effective for preventing the progression of joint damage in patients with active rheumatoid arthritis, suggest the results of two phase 3 studies.

Researchers presented data from the Abatacept in Inadequate Responders to Methotrexate (AIM) study — a one-year, randomized, double-blind, placebo-controlled trial — at the 2005 annual meeting of the European League Against Rheumatism. The results showed that abatacept, an investigational selective co-stimulation modulator, inhibited joint damage progression independent of baseline clinical, biochemical or radiographic characteristics, according to a press release from Bristol-Myers Squibb, developers of the drug.

The AIM study evaluated abatacept in 652 patients with active RA who had inadequately responded to treatment with methotrexate. Researchers randomly assigned patients to undergo 30-minute intravenous infusions of either 10 mg/kg of abatacept or placebo in addition to continuing methotrexate use. One additional disease-modifying antirheumatic drug was also allowed at six months follow-up, according to the press release.

Radiographic analysis, available for 391 abatacept-treated and 195 placebo-treated patients, indicated that the drug prevented progression of structural damage. Abatacept showed a significant effect on median change from baseline in joint erosion score (P=.029), joint space narrowing score (P=.009) and total score (P=.012). Additionally, abatacept patients had significantly fewer increases in mean scores for both joint erosion (P=.008) and joint space narrowing (P<.001) as well as for total score (P<.001), according to the release.

Both groups had similar rates of adverse events — primarily headaches, which were reported by 17.6% of abatacept and 11.9% of placebo patients. Other adverse events included nasopharyngitis in 15.2% of abatacept- and 11.4% of placebo-treated patients and nausea in 12% of abatacept- and 11% of placebo-treated patients.

Fifteen percent of abatacept and 11.9% of placebo patients experienced serious adverse events, which led 4.2% of abatacept and 1.8% of placebo patients to discontinue the study at one year, according to the release.

A second phase 3 study supports the safety profile of the drug. In the ASSURE trial, 959 patients received abatacept and one or more FDA-approved disease-modifying antirheumatic drugs (DMARD). Researchers compared these patients to 482 patients receiving placebo and DMARDs.

Overall, nine deaths occurred during the study — five abatacept patients and four placebo patients. Thirteen percent of abatacept patients and 12% of placebo patients experienced serious adverse events, most frequently musculoskeletal and connective tissue disorders. At one year, 5.3% of abatacept patients and 3.9% of placebo patients discontinued treatment due to serious adverse events, according to the press release.

For more information:
Genant H, Peterfy C, Paira S, et. al. Abatacept significantly inhibits structural damage progression as assessed by the genant-modified sharp scoring system in rheumatoid arthritis patients with inadequate methotrexate responses. #OP0001. Presented at the Annual European Congress of Rheumatology. June 8-11, 2005. Vienna, Austria.
Weinblatt M, Combe B, White A, et. al. Safety of abatacept in patients with active rheumatoid arthritis receiving background non-biologic and biologic DMARDs: one-year results of the ASSURE trial. #OP0012. Presented at the Annual European Congress of Rheumatology. June 8-11, 2005. Vienna, Austria.