This is a world wide study to evaluate the remission and joint damage in subjects treated with abatacept in addition to methotrexate versus subjects who receive methotrexate along with a placebo.
INTERVENTION: Drug: Abatacept plus methotrexate for the first 12 months. Month 12 to 24, subjects previously treated with Abatacept plus methotrexate remain on this same treatment. Study Design: Treatment, Randomized, Double‐Blind, Placebo Control, Parallel Assignment, Efficacy Study CONDITION: Rheumatoid Arthritis (RA) PRIMARY OUTCOME: Joint damage progression measured by radiographic evaluation using the Genantâ Modified Sharp total score The proportion of subjects who achieve remission in 12 months of treatment as defined by a DAS 28 score less that 2.6. SECONDARY OUTCOME: Assess the inhibition of joint damage progression measured by radiographic evaluation using the Genant‐modified Sharp erosion, joint space narrowing and total score. Compare the disease activity as measured by DAS 28 score. Compare the improvement in health‐related quality of life using SF‐36. Compare the improvement in physical function using the HAQ disability index. Compare the inhibition of joint damage progression measured by radiographic evaluation using the Genant‐modified Sharp erosion, and joint space narrowing. Compare the proportion of subjects achieving major clinical response defined by 6 months of consecutive ACR 70 response. Compare the proportion of subjects with an ACR50 response. Determine the safety and tolerability of abatacept in this subject population, including evaluation of immunogenicity of abatacept. INCLUSION CRITERIA: Diagnosis of rheumatoid arthritis (RA) <2 years; never received treatment with methotrexate; erosions noted on x‐ray. CRP >= 8.0 mg/L Rheumatoid factor or anti CCP positive.
OBJETIVOS: Evaluar la eficacia y seguridad de abatacept en pacientes no tratados previamente con metotrexato con artritis reumatoide (AR) y factores de mal pronóstico. MÉTODOS: En este estudio doble ciego, de fase IIIb estudio, los pacientes con AR de 2 años o menos fueron asignados al azar 1: 1 para recibir abatacept (aproximadamente 10 mg / kg) más metotrexato o placebo más metotrexato. Los pacientes fueron metotrexato ingenuo y seropositivos para el factor reumatoide (FR), anti-cíclica de proteínas citrulinado (PCC) tipo 2, o ambos, y tenían evidencia radiográfica de erosiones articulares. Los objetivos co-primarios fueron la proporción de pacientes que alcanzaron puntuación de actividad de la enfermedad en 28 articulaciones (DAS28)-definido remisión (proteína C reactiva) y la progresión del daño articular (Genant modificado índice total de Sharp; TS) en el año 1. La seguridad se supervisan a lo largo. RESULTADOS: Al inicio del estudio, los pacientes tenían una media de 6,3 DAS28, un TS media de 7,1 y la media de duración de la enfermedad de 6,5 meses, 96,5% y 89,0% de los pacientes eran de RF o anti-CCP2 seropositivos, respectivamente. En el año 1, una proporción significativamente mayor de abatacept más metotrexato pacientes tratados alcanzaron la remisión (41,4% vs 23,3%, p <0,001) y hubo progresión radiográfica significativamente menor (cambio medio en el TS 0,63 frente a 1,06, p = 0,040) en comparación con metotrexato sola. Más de 1 año, la frecuencia de eventos adversos (84,8% vs 83,4%), eventos adversos graves (7,8% vs 7,9%), infecciones graves (2,0% vs 2,0%), trastornos autoinmunes (2,3% vs 2,0%) y neoplasias ( 0,4% frente al 0%) fue comparable a abatacept más metotrexato en comparación con metotrexato solo. CONCLUSIONES: En una población con metotrexato ingenuo con AR temprana y factores de mal pronóstico, la combinación de abatacept y metotrexato proporciona una eficacia significativamente mayor clínico y radiográfico, en comparación con metotrexato solo y tenía un perfil similar, de seguridad favorable.
Purpose: Intensive treatment of patients early in the RA disease process is becoming a standard of care making disease remission, as a treatment goal, more attainable. Here we report the clinical and safety outcomes in methotrexate naïve patients with early erosive RA treated with a combination of abatacept + methotrexate through 24 months. Method: The AGREE trial was a 24 month study with a 12 month double-blind period (DB) and 12 month open label period (OL). During DB, patients were randomized to ABA (∼10 mg/kg dose based on weight range) + MTX (dosed up to 20 mg) or placebo (PLA) + MTX. All patients completing DB and entering OL received ABA + MTX. Safety was assessed in all pts receiving >=1 dose of ABA in OL. Clinical outcomes evaluated included DAS28 remission (DAS28 <2.6), low disease activity state (LDAS, DAS28 <= 3.2), and ACR responses. Results: All 459 pts completing DB entered OL; 94.3% completed OL. Remission, LDAS, and ACR responses were sustained or increased from 12 to 24 months in original ABA + MTX arm (Table), with over half (55.2%) in remission at 24 months. Proportion achieving these outcomes in the original MTX alone arm increased after initiating ABA in OL, with 44.5% in remission at 24 months. Rates (per 100 pt yrs) of serious AE (6.42 vs 8.35) and serious infections (1.73 vs 2.04) were similar in the OL vs DB respectively. Autoimmune events occurred at a similar rate in OL as in DB (1.30 vs 2.47, respectively). Two deaths occurred. No malignancies or TB were reported. (Table presented) Conclusion: Sustained disease remission is an achievable goal for many patients with early RA when treatment with combination of ABA + MTX is initiated early. Consistent with the long-term safety experience in patients with longer standing disease no new or unexpected safety signals occurred in this population. These data support the use of ABA + MTX in an early RA population.
Background: Intensive treatment of patients early in the RA disease process is becoming a standard of care making disease remission, as a treatment goal, more attainable. Here we report the clinical and safety outcomes in methotrexate naive patients with early erosive RA treated with a combination of abatacept + methotrexate through 24 months. Methods: The AGREE trial was a 24 month study with a 12 month double‐blind period (DB) and 12 month open label period (OL). During DB, patients were randomized to ABA (~10 mg/kg dose based on weight range) + MTX (dosed up to 20 mg) or placebo (PLA) + MTX. All patients completing DB and entering OL received ABA + MTX. Safety was assessed in all pts receiving >=1 dose of ABA in OL. Clinical outcomes evaluated included DAS28 remission (DAS28 < 2.6), low disease activity state (LDAS, DAS28 <=3.2), and ACR responses. Results: All 459 pts completing DB entered OL; 94.3% completed OL. Remission, LDAS, and ACR responses were sustained or increased from 12 to 24 months in original ABA + MTX arm (Table), with over half (55.2%) in remission at 24 months. Proportion achieving these outcomes in the original MTX alone arm increased after initiating ABA in OL, with 44.5% in remission at 24 months. Rates (per 100 pt years) of serious AE (6.42 versus 8.35) and serious infections (1.73 versus 2.04) were similar in the OL versus DB respectively. Autoimmune events occurred at a similar rate in OL as in DB (1.30 versus 2.47, respectively). Two deaths occurred. No malignancies or TB were reported. Table presented. Conclusion: Sustained disease remission is an achievable goal for many patients with early RA when treatment with combination of ABA + MTX is initiated early. Consistent with the long‐term safety experience in patients with longer standing disease no new or unexpected safety signals occurred in this population. These data support the use of ABA + MTX in an early RA population.
<b>OBJECTIVE: </b>To assess the efficacy and safety of abatacept plus methotrexate versus methotrexate alone in early erosive rheumatoid arthritis (RA). <b>METHODS: </b>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. <b>RESULTS: </b>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. <b>CONCLUSIONS: </b>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. <b>Trial Registration: </b>NCT00122382.
OBJECTIVE: This article reports 1-year clinical outcomes in the subgroup of patients with rheumatoid arthritis in the Abatacept study to Gauge Remission and joint damage progression in methotrexate-naive patients with Early Erosive rheumatoid arthritis (AGREE) who achieved radiographic nonprogression at the end of the double-blind phase.
METHODS: Patients who achieved radiographic nonprogression (change from baseline in total Sharp score ≤ 0 at 12 months) with abatacept plus methotrexate (MTX) or MTX alone were eligible for this analysis. Clinical outcomes were remission, defined by 28-joint Disease Activity Score (DAS28) using C-reactive protein (CRP), low Disease Activity Score (LDAS), American College of Rheumatology (ACR) scores, physical function (Health Assessment Questionnaire), and tender and swollen joint counts. Safety was assessed at each visit.
RESULTS: Patients in the abatacept plus MTX and MTX monotherapy groups had similar baseline characteristics and were similar to the overall study population. The proportion of patients who achieved DAS28 (CRP) remission or LDAS was greater with abatacept plus MTX vs MTX alone [43.2% vs 22.7% (p < 0.001) and 57.4% vs 40.6% (p = 0.008), respectively]. More patients receiving abatacept plus MTX achieved key ACR responses, including major clinical response (27.3% vs 11.9%; p < 0.001). Safety profiles were similar in both treatment groups.
CONCLUSION: More MTX-naive patients with early RA who achieved radiographic nonprogression taking abatacept plus MTX also achieved DAS28 (CRP)-defined remission and LDAS compared with patients who received MTX alone, supporting the use of abatacept as a first-line biologic in combination with disease-modifying antirheumatic drugs.
INTRODUCTION: This study evaluated various remission criteria in abatacept plus methotrexate (MTX)-treated patients with early rheumatoid arthritis (RA). We aimed to investigate the time to, and sustainability of, remission, and to evaluate the relationship between remission, function and structure.
METHODS: Post hoc analyses were performed from the 12-month, double-blind period of the Abatacept study to Gauge Remission and joint damage progression in methotrexate (MTX)-naive patients with Early Erosive rheumatoid arthritis (AGREE) in patients with early RA (≤2 years) and poor prognostic factors, comparing abatacept plus MTX (n = 210) versus MTX alone (n = 209).
RESULTS: At month 12, Disease Activity Score 28, Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index and Boolean remission rates were, for abatacept plus MTX versus MTX alone: 47.6 % versus 27.3 %, 33.3 % versus 12.4 %, 34.3 % versus 16.3 %, and 23.8 % versus 5.7 %, respectively. Cumulative probability demonstrated higher proportions achieving first remission and first sustained remission for abatacept plus MTX versus MTX alone (e.g., 23.3 % [95 % confidence interval (CI): 17.6, 29.1] vs 12.9 % [8.4, 17.5] for first SDAI remission over 0-6 months). For patients in SDAI remission at month 3, mean Health Assessment Questionnaire-Disability Index at month 12 was 0.20 versus 0.50 for abatacept plus MTX versus MTX alone. Mean changes in radiographic score from baseline to month 12 were minimal for patients in SDAI remission at month 3 in both groups, while less structural damage progression was seen, 0.75 versus 1.35, respectively, for abatacept plus MTX versus MTX alone for patients with moderate/high disease activity at month 3 (adjusted mean treatment difference: -0.60 [95 % CI: -1.11, -0.09; P < 0.05]).
CONCLUSIONS: High proportions of abatacept plus MTX-treated patients achieved stringent remission criteria. Remission was associated with long-term functional benefit; dissociation was seen between clinical and structural outcomes for abatacept. These findings highlight the impact of reaching stringent remission targets early, on physical function and structural damage, in MTX-naïve biologic-treated patients.
TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00122382. Registered 19 July 2005.
This is a world wide study to evaluate the remission and joint damage in subjects treated with abatacept in addition to methotrexate versus subjects who receive methotrexate along with a placebo.
