Clinical efficacy and safety of abatacept in methotrexate-naive patients with early rheumatoid arthritis and poor prognostic factors

Abstract

Objectives: To assess the efficacy and safety of abatacept in methotrexate-naive patients with early rheumatoid arthritis (RA) and poor prognostic factors.

Methods: In this double-blind, phase IIIb study, patients with RA for 2 years or less were randomly assigned 1 : 1 to receive abatacept (approximately 10 mg/kg) plus methotrexate, or placebo plus methotrexate. Patients were methotrexate-naive and seropositive for rheumatoid factor (RF), anti-cyclic citrullinated protein (CCP) type 2 or both and had radiographic evidence of joint erosions. The co-primary endpoints were the proportion of patients achieving disease activity score in 28 joints (DAS28)-defined remission (C-reactive protein) and joint damage progression (Genant-modified Sharp total score; TS) at year 1. Safety was monitored throughout.

Results: At baseline, patients had a mean DAS28 of 6.3, a mean TS of 7.1 and mean disease duration of 6.5 months; 96.5% and 89.0% of patients were RF or anti-CCP2 seropositive, respectively. At year 1, a significantly greater proportion of abatacept plus methotrexate-treated patients achieved remission (41.4% vs 23.3%; p<0.001) and there was significantly less radiographic progression (mean change in TS 0.63 vs 1.06; p = 0.040) versus methotrexate alone. Over 1 year, the frequency of adverse events (84.8% vs 83.4%), serious adverse events (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%) was comparable for abatacept plus methotrexate versus methotrexate alone.

Conclusions: In a methotrexate-naive population with early RA and poor prognostic factors, the combination of abatacept and methotrexate provided significantly better clinical and radiographic efficacy compared with methotrexate alone and had a comparable, favourable safety profile.

Conflict of interest statement

Competing interests: RW has received consulting fees and speaker’s bureau fees from Bristol-Myers Squibb and Schering-Plough and research support from UCB; ACX was a member of the national board as a consultant for Bristol-Myers Squibb (2003–7) and Abbott (2003–5); JW has received consulting fees from Bristol-Myers Squibb; JG-R is a member of advisory boards for Wyeth, Schering-Plough, Bristol-Myers Squibb and Roche and has received lecture fees from Abbott, Wyeth, Roche, Bristol-Myers Squibb and Schering-Plough; WG is a consultant for Bristol-Myers Squibb, Abbott Immunology, General Electric, Esaote and Schering-Plough, has received honorarium from Bristol-Myers Squibb, Abbott Immunology, General Electric, Schering-Plough and Wyeth and has received research support from Abbott Immunology and Wyeth; BH is a consultant and has received a grant/research support for Abbott Canada, Amgen Canada, Bristol-Myers Squibb Canada, Roche and Schering-Plough; WS is a speaker and principal investigator for Amgen, Wyeth, Abbott, Bristol-Myers Squibb, Centocor, Genentech and Biogen Idec; HG is a consultant for CCBR-SYNARC, Bristol-Myers Squibb, Wyeth, Roche, Servier, GlaxoSmithKline, Merck, Biogen Idec and Genentech and has stocks in CCBR-SYNARC; CP is an employee and has stocks in Synarc Inc; J-CB is an employee of BMS and owns stock options; AC and RH are employees of Bristol-Myers Squibb; JB is a consultant for Centocor and Riley, is on the advisory board for Abbott and Amgen, has received research support for Amgen, Biogen Idec and Bristol-Myers Squibb and has received honorarium for Abbott, Amgen, Centocor and Novartis. MR, SN, PD and SHP have nothing to disclose.

Figures

Figure 1

Patient disposition over 1 year. MTX, methotrexate.

Figure 2

Summary of clinical efficacy. Proportion of patients in the abatacept plus methotrexate (MTX) and methotrexate alone groups over 1 year achieving (A) Disease activity score in 28 joints (DAS28, C-reactive protein)-defined remission; (B) American College of Rheumatology (ACR) 50; (C) ACR70; and (D) ACR90. Data are based on the intent-to-treat population, including all patients randomly assigned and treated. Patients who discontinued were considered non-responders. p Values represent abatacept plus methotrexate versus methotrexate alone. Error bars represent 95% CI. *p

Figure 3

Inhibition of radiographic progression. Mean change from baseline at month 6 and year 1 for (A) total score (TS); (B) erosion score (ES); (C) joint-space narrowing (JSN) and (D) cumulative probability distribution of changes from baseline in Genant-modified total Sharp scores by treatment at year 1. p Values represent abatacept plus methotrexate (MTX) versus methotrexate alone at year 1. *Based on as-observed data. †Missing data were imputed by linear extrapolation.