Clinical Geriatrics

American College of Rheumatology/Association of Rheumatology Health Professionals Annual Meeting
Philadelphia, PA; October 17-21, 2009

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Sustained Response in Early Rheumatoid Arthritis with Abatacept

Philadelphia, PA—Two-year data from the AGREE (Abatacept Study to Gauge Remission and Joint Damage Progression in Methotrexate-Naïve Patients with Early Erosive Rheumatoid Arthritis) trial show that patients treated with abatacept in combination with methotrexate (MTX) achieved sustained low disease activity scores at 24 months. Results of the study, which compared treatment with abatacept + MTX versus treatment with MTX alone in MTX-naïve patients with early erosive rheumatoid arthritis (RA) ≤ 2 years duration, were presented at the ACR/ARHP Scientific meeting.

The 24-month study included a 12-month double-blind period during which patients were randomized to receive 10 mg/kg of abatacept + up to 20 mg of MTX or MTX and placebo. Patients who completed the double-blind stage entered a 12-month open-label period and received abatacept + MTX. Of the 256 abatacept-treated and 253 placebo-treated patients who completed the 1-year, randomized, double-blind active control period, 232 abatacept- and 227 placebo-treated patients entered the open-label period. Of these patients, 94.3% completed the open-label period.

The coprimary end points of the double-blind period (year 1) of the AGREE trial were the proportion of patients achieving a Disease Activity Score 28 using C-reactive protein (DAS28-CRP) of < 2.6 and assessment of structural damage using the Genant-modified Total Sharp Score. At year 1 of the trial, 41.4% in the abatacept + MTX group versus 23.3% of patients treated with MTX alone achieved a DAS28-CRP of < 2.6 (P < 0.001). Of patients who initially received abatacept + MTX, 55.2% achieved DAS28-CRP of < 2.6 by the end of year 2. Of these patients, more than half had no active joints. The proportion achieving these outcomes in the original MTX-alone arm increased after initiating abatacept in the open-label period, with 44.5% in remission at 24 months.

The data also showed that abatacept + MTX can inhibit radiographic progression of RA and improve physical function in addition to relieving pain, swelling, and fatigue. Of patients treated with abatacept + MTX who achieved a DAS28-CRP of < 2.6, there were 54% with no active joints, 17% had one active joint, 7% had three active joints, and 22% had three or more active joints. Mean change from baseline in Genant-modified Total Sharp Score (TS) was lower for patients in the group treated with abatacept + MTX (0.6) versus the group treated with MTX alone (1.1; P = 0.040). Of patients treated with abatacept + MTX who achieved a DAS28-CRP of < 2.6, there were 63.5% with no active joints, 11.9% with one active joint, and 24.6% with two or more active joints, where an active joint was tender or swollen. Joint damage progression was also measured using the TS, which uses X-rays to measure change at year 1. Nonprogression was defined as a TS of ≤ 0.0. Radiographic data read in a blinded manner demonstrated that 56.8% of patients treated with abatacept + MTX for 24 months were nonprogressors.

In the AGREE study, American College of Rheumatology (ACR) 50 and 70 scores (50% and 70% improvement in signs and symptoms) were also reported at 24 months. Of the 232 patients who achieved ACR scores, 74.1% in the abatacept + MTX group achieved ACR 50 and 53.9% achieved ACR 70.

The safety profile for the open-label period was similar to the double-blind period of the study. Overall, incidence rates per 100 patient-years of exposure to abatacept of serious adverse events (8.4% vs 6.4%) and serious infections (2.0% vs 1.7%) were similar in the double-blind and open-label periods, respectively. Autoimmune events occurred at a similar rate in the double-blind and open-label periods (2.5% vs 1.3%, respectively).