Abatacept for rheumatoid arthritis refractory to tumor necrosis factor alpha
inhibition.
Author(s): Genovese MC, Becker JC, Schiff M, Luggen M, Sherrer Y, Kremer J, Birbara C, Box
J, Natarajan K, Nuamah I, Li T, Aranda R, Hagerty DT, Dougados M.
Affiliation(s): Stanford University Medical Center, Stanford, Calif, USA. genovese@stanford.edu
Publication date & source: 2005, N Engl J Med. , 353(11):1114-23
BACKGROUND: A substantial number of patients with rheumatoid arthritis have an
inadequate or unsustained response to tumor necrosis factor alpha (TNF-alpha)
inhibitors. We conducted a randomized, double-blind, phase 3 trial to evaluate
the efficacy and safety of abatacept, a selective costimulation modulator, in
patients with active rheumatoid arthritis and an inadequate response to at least
three months of anti-TNF-alpha therapy.
METHODS: Patients with active rheumatoid arthritis and an inadequate response to
anti-TNF-alpha therapy were randomly assigned in a 2:1 ratio to receive abatacept
or placebo on days 1, 15, and 29 and every 28 days thereafter for 6 months, in
addition to at least one disease-modifying antirheumatic drug. Patients
discontinued anti-TNF-alpha therapy before randomization. The rates of American
College of Rheumatology (ACR) 20 responses (indicating a clinical improvement of
20 percent or greater) and improvement in functional disability, as reflected by
scores for the Health Assessment Questionnaire (HAQ) disability index, were
assessed.
RESULTS: After six months, the rates of ACR 20 responses were 50.4 percent in the
abatacept group and 19.5 percent in the placebo group (P<0.001); the respective
rates of ACR 50 and ACR 70 responses were also significantly higher in the
abatacept group than in the placebo group (20.3 percent vs. 3.8 percent, P<0.001;
and 10.2 percent vs. 1.5 percent, P=0.003). At six months, significantly more
patients in the abatacept group than in the placebo group had a clinically
meaningful improvement in physical function, as reflected by an improvement from
baseline of at least 0.3 in the HAQ disability index (47.3 percent vs. 23.3
percent, P<0.001). The incidence of adverse events and peri-infusional adverse
events was 79.5 percent and 5.0 percent, respectively, in the abatacept group and
71.4 percent and 3.0 percent, respectively, in the placebo group. The incidence
of serious infections was 2.3 percent in each group.
CONCLUSIONS: Abatacept produced significant clinical and functional benefits in
patients who had had an inadequate response to anti-TNF-alpha therapy.
Erratum in
N Engl J Med. 2005 Nov 24;353(21):2311.
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