RESUMO
OBJECTIVES: This randomised, double-blind, placebo-controlled phase IIIb study evaluated the impact of abatacept on MRI pathology as a primary outcome in methotrexate (MTX)-refractory patients with rheumatoid arthritis. METHODS: Patients received intravenous abatacept (â¼10 mg/kg) or placebo, on background MTX, for 4 months, followed by an 8-month open-label extension (OLE; all patients received abatacept plus MTX). Patients had 1.5T MRI with intravenous contrast at baseline, Months 4 and 12; wrist synovitis (three locations assessed), and wrist and hand (15 and eight locations assessed, respectively) osteitis and erosion were scored using OMERACT-RAMRIS. RESULTS: 26/27 abatacept- and 23/23 placebo-randomised patients completed Month 4 and entered the OLE; 26 and 21 completed Month 12. The primary endpoint was not achieved; mean change (SD) from baseline in synovitis was -0.44 (1.47) for abatacept versus 0.52 (1.38) for placebo (p=0.103) at Month 4. For mean change in synovitis adjusted for baseline score (sensitivity analysis), the difference between groups was -0.69, p=0.078. Adjusted mean changes (SE) in osteitis and erosion were -1.94 (0.86) and 0.45 (0.43) for abatacept, and 1.54 (0.90) and 0.95 (0.45) for placebo. Further MRI improvements were observed up to Month 12 for abatacept and from Months 4 to 12 for placebo-treated patients switched to abatacept at Month 4. Clinical efficacy was shown with abatacept and sustained to Month 12. CONCLUSIONS: Despite small patient numbers, MRI detected structural and synovial benefit, sustained to Month 12 in abatacept+MTX-treated patients, and improvements in structural and inflammatory outcomes for placebo+MTX-treated patients following addition of abatacept. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov NCT00420199.
Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Imunoconjugados/uso terapêutico , Metotrexato/uso terapêutico , Osteíte/tratamento farmacológico , Sinovite/tratamento farmacológico , Articulação do Punho/efeitos dos fármacos , Abatacepte , Artrite Reumatoide/complicações , Artrite Reumatoide/patologia , Método Duplo-Cego , Resistência a Medicamentos , Substituição de Medicamentos , Quimioterapia Combinada , Feminino , Humanos , Injeções Intravenosas , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Osteíte/etiologia , Osteíte/patologia , Sinovite/etiologia , Sinovite/patologia , Resultado do Tratamento , Articulação do Punho/patologiaRESUMO
OBJECTIVE: To evaluate abatacept treatment over 3 years in patients with rheumatoid arthritis (RA) refractory to methotrexate (MTX). METHODS: Patients randomised to abatacept or placebo (+MTX) during the 1-year double-blind period of the Abatacept in Inadequate responders to Methotrexate (AIM) trial received open-label abatacept (+MTX) in the long-term extension (LTE). Safety was assessed for patients who received ≥ 1 dose of abatacept, regardless of randomisation group. Efficacy was assessed for patients randomised to abatacept who entered the LTE. RESULTS: 433 and 219 patients were randomised and treated with abatacept or placebo, respectively; 378 and 161 entered the LTE. At year 3, 440/539 patients were ongoing. No unexpected safety events were observed in the LTE. By year 3, incidence rates of adverse event and serious adverse events were 249.8/100 and 15.1/100 patient-years, respectively. Incidence rates were generally stable over time. At year 3, 84.8%, 63.4% and 37.5% of patients achieved American College of Rheumatology (ACR) criteria of 20, 50 and 70, respectively, compared with 82.3%, 54.3% and 32.4% of patients at year 1. Mean changes in Genant-modified Sharp scores were reduced progressively over 3 years, with significantly greater inhibition during year 3 compared with year 2 (p=0.022 for total score). CONCLUSION: In MTX-inadequate responders with RA, abatacept provided consistent safety and sustained efficacy over 3 years. The data suggest an increasing inhibitory disease-modifying effect on radiographic progression.
Assuntos
Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Imunoconjugados/efeitos adversos , Imunossupressores/efeitos adversos , Abatacepte , Adulto , Antirreumáticos/uso terapêutico , Artrite Reumatoide/diagnóstico por imagem , Doenças Autoimunes/induzido quimicamente , Progressão da Doença , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Imunoconjugados/uso terapêutico , Imunossupressores/uso terapêutico , Masculino , Metotrexato/efeitos adversos , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Neoplasias/induzido quimicamente , Infecções Oportunistas/induzido quimicamente , Qualidade de Vida , Radiografia , Índice de Gravidade de Doença , Falha de Tratamento , Resultado do TratamentoRESUMO
OBJECTIVE: The prognostic implications of carotid plaque calcification (CPC) relative to subsequent vascular events are unclear. Our aim was to determine the association between CPC and risk of vascular events in a prospective multi-ethnic cohort. METHODS: CPC was assessed among 1118 stroke-free subjects (mean age 68+/-8 years; 59% women; 59% Hispanic, 22% black, 19% white) from the Northern Manhattan Study using high-resolution B-mode ultrasound. CPC was defined by presence of any acoustic shadowing associated with carotid plaque, producing a reduction in echo amplitude due to intervening structures with high attenuation. Using Cox proportional hazards models, hazard ratios (HR) were estimated for the combined vascular outcome, defined as ischemic stroke (IS), myocardial infarction (MI) or vascular death (VD). RESULTS: Carotid plaque was present in 637 (57%) subjects. CPC was present in 225 subjects (20% of total cohort; 35% of those with plaque). During a mean follow-up time of 2.7 years, the combined vascular outcome occurred among 52 subjects (20 IS, 22 MI, and 24 VD). Adjusting for demographics, major vascular risk factors, and carotid intima media thickness, those with CPC (in comparison to those without plaque) had a significantly increased risk of the combined vascular outcome (HR 2.5, 95% CI 1.0-5.8). CONCLUSIONS: In this population-based cohort, the presence of calcified carotid plaque, as assessed by high-resolution B-mode ultrasound, was an independent predictor of vascular events. It may serve as a simple and non-invasive marker of increased atherosclerotic risk and further aid in vascular risk stratification.