Sustained disease remission and inhibition of radiographic progression in methotrexate-naive patients with rheumatoid arthritis and poor prognostic factors treated with abatacept: 2-year outcomes.

OBJECTIVE: To assess the efficacy and safety of abatacept plus methotrexate versus methotrexate alone in early erosive rheumatoid arthritis (RA). METHODS: The AGREE was a 2-year phase IIIb multinational study in early (≤ 2 years) RA. During the double-blind period (year 1), patients were randomly assigned 1:1 to receive abatacept+methotrexate or methotrexate alone; all patients received open-label abatacept+methotrexate during year 2. Clinical outcomes assessed included 28-joint disease activity score (DAS28) defined remission, low disease activity score (LDAS), American College of Rheumatology (ACR) responses and physical function. Radiographic outcomes were assessed using the Genant-modified Sharp total score (TS). Safety was monitored throughout. RESULTS: Of the 459 patients completing year 1, 433 patients (94.3%) completed year 2. DAS28-defined remission, LDAS, ACR and physical function were sustained through year 2 in the original abatacept+methotrexate group, with 55.2% in remission at 2 years. Upon introduction of abatacept in the methotrexate-alone group, additional patients achieved DAS28-defined remission (44.5% vs 26.9%), LDAS (60.4% vs 43.2%) and improved ACR 70 (49.8% vs 31.7%) for year 2 versus year 1. Less radiographic progression was observed at 2 years in the original abatacept+methotrexate group than the methotrexate-alone group (change in TS 0.84 vs 1.75, p<0.001). No new safety issues were seen. Similar rates of serious adverse events, serious infections and autoimmune events were observed in years 1 and 2. CONCLUSIONS: The AGREE trial was the first to examine the impact of T-cell co-stimulation modulation with abatacept in patients with early erosive RA. Early treatment with abatacept+methotrexate resulted in greater sustainable clinical, functional and radiographic benefits than methotrexate alone, with acceptable safety and tolerability. TRIAL REGISTRATION: NCT00122382.

Greater remission rates in patients with early versus long-standing disease in biologic-naive rheumatoid arthritis patients treated with abatacept: a post hoc analysis of randomized clinical trial data.

OBJECTIVES: Current aim of rheumatoid arthritis (RA) treatment is to achieve remission in as many patients as possible. Rates of remission and clinical outcomes after treatment with abatacept in biologic-naive rheumatoid arthritis (RA) patients with early disease and an inadequate response to methotrexate (MTX) versus patients with ≥ 10 years of disease were assessed. METHODS: Data from two trials assessing the efficacy of abatacept in MTX inadequate responders were pooled for this exploratory post hoc analysis. Patients with disease duration of ≤ 2 years at baseline (early disease), originally assigned to an abatacept approximately 10 mg/kg treatment arm and entered into a long-term extension (LTE), were compared with patients with ≥ 10 years of disease (long-standing RA). Remission, DAS28-CRP, ACR 70 responses and the Routine Assessment of Patient Index Data 3 (RAPID3), improvement in physical function as measured by the Health Assessment Questionnaire Disability Index (HAQ-DI). RESULTS: Twenty-three percent of these patients (n=108) had early disease. A higher percentage of patients with early disease achieved DAS28-CRP remission versus patients with long-standing disease (35.2% vs. 19.4% at year 1, p<0.01; 46.0% vs. 30.9% at year 3, p<0.05). In addition, a higher percentage of the subgroup with early RA achieved ACR70 responses. More patients with early RA had a meaningful improvement in their HAQ-DI (75.2% vs. 60.4%; p<0.05) and RAPID3 scores at one year (mean changes from baseline of -9.6 vs. -8.1; p=0.009). CONCLUSIONS: These data provide additional support for the possible use of abatacept in biologic-naive patients who have had inadequate response to MTX, earlier in their disease course.