<b>BACKGROUND: </b>The selective co-stimulation modulator abatacept demonstrated efficacy for treating rheumatoid arthritis in early clinical studies.<b>OBJECTIVE: </b>To evaluate the effects of abatacept in patients with persistent, active rheumatoid arthritis despite methotrexate treatment.<b>DESIGN: </b>One-year, multicenter, randomized, double-blind, placebo-controlled trial (November 2002 to October 2004).<b>SETTING: </b>116 centers worldwide.<b>PATIENTS: </b>652 patients with active rheumatoid arthritis despite methotrexate treatment.<b>Intervention: </b>Once-monthly infusion of a fixed dose of abatacept, approximately 10 mg/kg of body weight, or placebo.<b>Measurements: </b>Co-primary end points were a 20% improvement in American College of Rheumatology (ACR) response criteria (ACR 20) at 6 months, clinically meaningful improvements in physical function, and change from baseline in joint erosion score at 1 year.<b>RESULTS: </b>Four hundred thirty-three and 219 patients were randomly assigned to abatacept or placebo, respectively, and 385 (89%) and 162 (74%), respectively, completed 1 year of treatment. In a modified intention-to-treat analysis, 6-month ACR 20, ACR 50, and ACR 70 responses were 67.9% for abatacept versus 39.7% for placebo (difference, 28.2 percentage points [95% CI, 19.8 to 36.7 percentage points]), 39.9% for abatacept versus 16.8% for placebo (difference, 23.0 percentage points [CI, 15.0 to 31.1 percentage points]), and 19.8% for abatacept versus 6.5% for placebo (difference, 13.3 percentage points [CI, 7.0 to 19.5 percentage points]), respectively. At 1 year, the responses increased to 73.1% for abatacept versus 39.7% for placebo (difference, 33.4 percentage points [CI, 25.1 to 41.7 percentage points]), 48.3% for abatacept versus 18.2% for placebo (difference, 30.1 percentage points [CI, 21.8 to 38.5 percentage points]), and 28.8% for abatacept versus 6.1% for placebo (difference, 22.7 percentage points [CI, 15.6 to 29.8 percentage points]), respectively (P < 0.001 for all). Physical function significantly improved in 63.7% versus 39.3% of patients (P < 0.001). At 1 year, abatacept statistically significantly slowed the progression of structural joint damage compared with placebo. Abatacept-treated patients had a similar incidence of adverse events (87.3% vs. 84.0%; difference, 3.3 percentage points [CI, -2.5 to 9.1 percentage points]) and a higher incidence of prespecified serious infections (2.5% vs. 0.9%; difference, 1.6 percentage points [CI, -0.3 to 3.6 percentage points]) and infusion reactions (acute, 8.8% vs. 4.1%; difference, 4.7 percentage points [CI, 0.9 to 8.4 percentage points]; peri-infusional, 24.5% vs. 16.9%; difference, 7.6 percentage points [CI, 1.2 to 14.0 percentage points]) compared with placebo recipients.<b>Limitations: </b>The study involved only 1 group of patients over 1 year.<b>CONCLUSIONS: </b>Abatacept statistically significantly reduced disease activity in patients with rheumatoid arthritis and an inadequate response to methotrexate. Longer treatment in different patient populations is needed to establish its appropriate role in rheumatoid arthritis.
OBJECTIVE: To determine the minimal clinically important differences (MCID) in the patient-reported outcomes of activity (0-30, number of days of limitation), fatigue (0 = none, 100 = complete), and sleep quality (0 = no problems, 100 = worst case) for patients with rheumatoid arthritis (RA).
METHODS: Two randomized controlled trials comparing abatacept to placebo in RA patients were considered: ATTAIN (n = 391) and AIM (n = 652). An internal anchor-based approach was used to derive the MCID using the Health Assessment Questionnaire, patient global assessment, and pain as anchors. Minimal important change in activity, fatigue, and sleep were determined by estimating mean changes in these outcomes in patients showing change in a narrow range about the MCID of the internal anchor. Correlation analysis was used to determine the consistency of the changes in the outcomes and anchors, and a Delphi process was used to determine the final MCID values.
RESULTS: For the 2 trials, consistent patterns of change for activity, fatigue, and sleep and the internal anchors were found with correlations in the range of 0.5, 0.7, and 0.4, respectively. The mean changes for activity, fatigue, and sleep in a narrow range about the MCID of the 3 internal anchors corresponding to the 2 trials were: 3.4 to 4.3 for activity; 6.7 to 17.0 for fatigue; and 4.1 to 7.3 for sleep. Following the Delphi process the MCID determined were 4 for activity, 10 for fatigue, and 6 for sleep.
CONCLUSION: These MCID for activity limitation, fatigue, and sleep problems can be used in designing clinical trials and providing benchmarks in assessing patient improvement.
OBJECTIVE: To examine the impact of added abatacept treatment on health related quality of life (HRQoL) in patients with rheumatoid arthritis (RA) who have inadequate response to methotrexate (MTX). METHODS: The impact of abatacept treatment on HRQoL was examined in a longitudinal, randomised double blind, placebo controlled clinical trial. Effects of treatment on HRQoL were examined using repeated measures analysis of covariance and comparing rates of change in HRQoL across treatment groups. The relationship between American College of Rheumatology (ACR) clinical markers and disease duration with changes in HRQoL indicators was also examined. Finally, a responder analysis was used to examine the percentage of patients who improved by 0.5 SD in 12 months or who reached the normative levels seen in the US general population. RESULTS: Statistically significant improvements in the abatacept group relative to controls were observed across a range of HRQoL measures, including physical function, fatigue, all eight domains of the SF-36, and the physical and mental component summaries (PCS and MCS). Improvements were seen as early as day 29 for fatigue and for five out of eight SF-36 domains. By day 169, all HRQoL measures were significantly better with abatacept than with placebo. HRQoL gains were associated with greater ACR clinical improvement, and the effects were consistent for patients with different disease duration. A significantly greater percentage of patients treated with abatacept reached normative levels of PCS, MCS, physical functioning, and fatigue compared with patients treated with MTX alone. CONCLUSION: Combined abatacept and MTX treatment produces significant improvements across a wide range of HRQoL domains in patients with RA.
OBJECTIVES: The aims of this study were to examine the relationship between external home help (EHH) use (ie, help provided by someone other than family or friends) and clinical response and patient-reported outcomes in patients with rheumatoid arthritis (RA), and to determine whether abatacept treatment in addition to methotrexate reduces the need for EHH.
METHODS: EHH use was recorded monthly in the Abatacept in Inadequate responders to Methotrexate (AIM) trial, a 12-month, randomized, double-blind, placebo-controlled trial of abatacept in patients with active RA also receiving methotrexate. Clinical response was defined using American College of Rheumatology (ACR) criteria, European League Against Rheumatism (EULAR) criteria, and Disease Activity Scale (DAS)-28 score. Patient-reported outcomes included the Health Assessment Questionnaire (HAQ), 100-mm visual analog scales (VASs) for pain and fatigue, and the Medical Outcomes Study 36-item Short Form Health Survey (SF-36) for health-related quality of life. Analysis of covariance and regression analysis were performed to investigate the relationship between change in EHH use and both clinical response and patient-reported outcomes.
RESULTS: Of 590 patients enrolled in the study, 232 (39.3%) were receiving EHH at baseline (mean age, 50.2 years; 88% female; 85% white; mean duration of RA, 8.8 years; mean [SD] EHH use, 15.6 [11.3] days). The level of EHH use was consistently higher with poorer scores on the HAQ, pain and fatigue VASs, DAS28, and SF-36. At 12 months, the mean reduction from baseline in EHH use was significantly greater in patients with ACR-50 or ACR-70 clinical response, EULAR good or moderate response, DAS28 remission, and clinically meaningful improvements in patient-reported outcomes. On multiple regression analysis, change in SF-36 Physical Functioning subscale score was the most important contributor to change in EHH after adjustment for other variables. The mean reduction from baseline in EHH use was significantly greater with abatacept compared with placebo over the study period (all, P<0.001).
CONCLUSIONS: In this exploratory analysis of data from patients with active RA from the AIM trial, EHH use was decreased significantly with improvements in clinical response, disease activity, and patient-reported outcomes. Treatment with abatacept in addition to methotrexate was associated with significantly decreased EHH use, suggesting that abatacept may have been associated with improved function and increased physical independence in these patients with RA.
Conference»American College of Rheumatology/Association of Rheumatology Health Professionals Annual Scientific Meeting; Atlanta, Georgia; 2010. Published in: Arthritis & Rheumatism
<b>OBJECTIVE: </b>To evaluate abatacept treatment over 3 years in patients with rheumatoid arthritis (RA) refractory to methotrexate (MTX).<b>METHODS: </b>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.<b>RESULTS: </b>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).<b>CONCLUSION: </b>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.
The selective co-stimulation modulator abatacept demonstrated efficacy for treating rheumatoid arthritis in early clinical studies.
OBJECTIVE:
To evaluate the effects of abatacept in patients with persistent, active rheumatoid arthritis despite methotrexate treatment.
DESIGN:
One-year, multicenter, randomized, double-blind, placebo-controlled trial (November 2002 to October 2004).
SETTING:
116 centers worldwide.
PATIENTS:
652 patients with active rheumatoid arthritis despite methotrexate treatment.Intervention: Once-monthly infusion of a fixed dose of abatacept, approximately 10 mg/kg of body weight, or placebo.Measurements: Co-primary end points were a 20% improvement in American College of Rheumatology (ACR) response criteria (ACR 20) at 6 months, clinically meaningful improvements in physical function, and change from baseline in joint erosion score at 1 year.
RESULTS:
Four hundred thirty-three and 219 patients were randomly assigned to abatacept or placebo, respectively, and 385 (89%) and 162 (74%), respectively, completed 1 year of treatment. In a modified intention-to-treat analysis, 6-month ACR 20, ACR 50, and ACR 70 responses were 67.9% for abatacept versus 39.7% for placebo (difference, 28.2 percentage points [95% CI, 19.8 to 36.7 percentage points]), 39.9% for abatacept versus 16.8% for placebo (difference, 23.0 percentage points [CI, 15.0 to 31.1 percentage points]), and 19.8% for abatacept versus 6.5% for placebo (difference, 13.3 percentage points [CI, 7.0 to 19.5 percentage points]), respectively. At 1 year, the responses increased to 73.1% for abatacept versus 39.7% for placebo (difference, 33.4 percentage points [CI, 25.1 to 41.7 percentage points]), 48.3% for abatacept versus 18.2% for placebo (difference, 30.1 percentage points [CI, 21.8 to 38.5 percentage points]), and 28.8% for abatacept versus 6.1% for placebo (difference, 22.7 percentage points [CI, 15.6 to 29.8 percentage points]), respectively (P < 0.001 for all). Physical function significantly improved in 63.7% versus 39.3% of patients (P < 0.001). At 1 year, abatacept statistically significantly slowed the progression of structural joint damage compared with placebo. Abatacept-treated patients had a similar incidence of adverse events (87.3% vs. 84.0%; difference, 3.3 percentage points [CI, -2.5 to 9.1 percentage points]) and a higher incidence of prespecified serious infections (2.5% vs. 0.9%; difference, 1.6 percentage points [CI, -0.3 to 3.6 percentage points]) and infusion reactions (acute, 8.8% vs. 4.1%; difference, 4.7 percentage points [CI, 0.9 to 8.4 percentage points]; peri-infusional, 24.5% vs. 16.9%; difference, 7.6 percentage points [CI, 1.2 to 14.0 percentage points]) compared with placebo recipients.Limitations: The study involved only 1 group of patients over 1 year.
CONCLUSIONS:
Abatacept statistically significantly reduced disease activity in patients with rheumatoid arthritis and an inadequate response to methotrexate. Longer treatment in different patient populations is needed to establish its appropriate role in rheumatoid arthritis.
