In patients with early rheumatoid arthritis (RA) and poor prognostic factors who had not received methotrexate (MTX), the combination of abatacept and MTX was more effective and as safe as MTX alone, according to the results of a double-blind, phase 3b study published online January 5 in the Annals of Rheumatic Diseases.
"The initiation of intensive treatment early in the course of disease is now an accepted paradigm in the treatment of RA, with an increasing emphasis on tight disease control and clinical remission as a treatment goal," write Rene Westhovens, MD, PhD, from the UZ Gasthuisberg in Belgium, and colleagues. "Abatacept is a soluble, fully human, recombinant fusion protein that selectively modulates the CD80/CD86:CD28 co-stimulatory signal for T-cell activation. The ability of abatacept to modulate the activation of T cells, including naive T cells, and the role of T cells in initiating disease suggests that abatacept has the potential to impact the progression of pathology early in the course of disease."
Inclusion criteria were duration of RA not more than 2 years; no previous treatment with MTX; seropositivity for rheumatoid factor (RF), anticyclic citrullinated protein (CCP) 2, or both; and radiographic evidence of joint erosions. Patients were randomly assigned in a 1:1 ratio to receive abatacept (~10 mg/kg) plus MTX or to receive placebo plus MTX. The main outcome measures were the proportion of patients achieving remission, defined by Disease Activity Score (DAS) 28-(C-reactive protein), and joint damage progression, defined by Genant-Modified Sharp total score (TS), at year 1. Safety outcomes were also assessed throughout treatment.
Mean DAS28 was 6.3, mean TS was 7.1, and mean disease duration was 6.5 months at baseline; 96.5% of patients were seropositive for RF, and 89.0% for anti-CCP2. At year 1, remission had occurred in 41.4% of the abatacept plus MTX group and in 23.3% of the placebo plus MTX group (P < .001). The abatacept plus MTX group also had significantly less radiographic progression (mean change in TS, 0.63 vs 1.06; P =.040).
Safety during 1 year was comparable in both groups, with a similar frequency of adverse events (AEs; 84.8 vs 83.4%), serious AEs (7.8 vs 7.9%), serious infections (2.0 vs 2.0%), autoimmune disorders (2.3 vs 2.0%), and malignancies (0.4 vs 0%).
Study limitations include relatively a short duration, limiting the ability to determine longer-term structural changes or to detect infrequent safety-related events. This group of patients with a poor prognosis is being followed during the second year of this 2-year trial.
"In a MTX-naive population with early RA and poor prognostic factors, the combination of abatacept and MTX provided significantly better clinical and radiographic efficacy compared with MTX alone, and had a comparable, favorable safety profile," the study authors write. "Coupled with a safety and tolerability profile comparable to MTX alone, these data support the early use of abatacept in RA patients with moderate to severe disease."
Bristol-Myers Squibb funded editorial assistance, employs 3 of the study authors, and has various financial relationships with some other study authors. Some of the study authors report various financial relationships with Schering-Plough, UCB, Abbott, Wyeth, Roche, Abbott Immunology, General Electric, Esaote, Abbott Canada, Amgen Canada, Bristol-Myers Squibb Canada, Amgen, Centocor, Genentech, Biogen Idec, CCBR-SYNARC, Servier, GlaxoSmithKline, Merck, Riley, and/or Novartis.
Ann Rheum Dis. Published online January 5,