To evaluate the efficacy and safety of adalimumab (D2E7), a fully human monoclonal
tumor necrosis factor alpha antibody, in combination with methotrexate (MTX) in patients
with active rheumatoid arthritis (RA) despite treatment with MTX.
In a 24-week, randomized, double-blind, placebo-controlled study, 271 patients with
active RA were randomly assigned to receive injections of adalimumab (20 mg, 40 mg,
or 80 mg subcutaneously) or placebo every other week while continuing to take their
long-term stable dosage of MTX. The primary efficacy end point was the American College
of Rheumatology criteria for 20% improvement (ACR20) at 24 weeks.
An ACR20 response at week 24 was achieved by a significantly greater proportion of
patients in the 20-mg, 40-mg, and 80-mg adalimumab plus MTX groups (47.8%, 67.2%,
and 65.8%, respectively) than in the placebo plus MTX group (14.5%) (P < 0.001). ACR50
response rates with the 20-mg, 40-mg, and 80-mg adalimumab dosages (31.9%, 55.2%,
and 42.5%, respectively) were significantly greater than that with placebo (8.1%)
(P = 0.003, P < 0.001, and P < 0.001, respectively). The 40-mg and 80-mg doses of
adalimumab were associated with an ACR70 response (26.9% and 19.2%, respectively)
that was statistically significantly greater than that with placebo (4.8%) (P < 0.001
and P = 0.020). Responses were rapid, with the greatest proportion of adalimumab-treated
patients achieving an ACR20 response at the first scheduled visit (week 1). Adalimumab
was safe and well tolerated; comparable numbers of adalimumab-treated patients and
placebo-treated patients reported adverse events.
The addition of adalimumab at a dosage of 20 mg, 40 mg, or 80 mg administered subcutaneously
every other week to long-term MTX therapy in patients with active RA provided significant,
rapid, and sustained improvement in disease activity over 24 weeks compared with MTX
plus placebo.