Long-term safety, efficacy and inhibition of radiographic progression with abatacept treatment in patients with rheumatoid arthritis and an inadequate response to methotrexate: 3-year results from the AIM trial

Abstract

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.

Figure 1

Clinical efficacy and patient-reported outcomes in abatacept-treated patients. (A) Proportion of patients achieving American College of Rheumatology (ACR) 20, 50 and 70 responses over 3 years. (B) Proportion of patients achieving low disease activity state (LDAS) and Disease Activity Score 28 (DAS28) (C reactive protein (CRP))-defined remission over 3 years. (C) Mean change from baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) over 3 years. (D) Mean change from baseline in the physical component summary (PCS), mental component summary (MCS) and Short Form (SF)-36 individual subscales at years 1 and 3. Data are presented with 95% CIs for patients randomised to abatacept who entered the long-term extension (LTE) to receive ≥1 dose of abatacept, with available assessments at the visit of interest (as-observed population). LDAS defined as DAS28 (CRP) ≤3.2. DAS28-defined remission defined as DAS28 (CRP) <2.6. At year 1, 370, 370, 373, 372, 373, 373, 373, 373, 370 and 373 patients were included in the PCS, MCS, physical function, role–physical, bodily pain, general health, vitality, social functioning, role–emotional and mental health assessments, respectively. At year 3, 308, 308, 310, 309, 309, 312, 312, 312, 309 and 312 patients were included in the aforementioned assessments, respectively. A change of 3.0 units in MCS and PCS was considered the minimum clinically important difference (MCID).

Figure 2

Impact on radiographic disease progression over 3 years of abatacept treatment. (A) Mean change from baseline in Genant-modified Sharp total score. (B) Mean change in erosion score. (C) Mean change in joint space narrowing score. (D) Cumulative probability plot showing change from baseline in total score. Data based on all patients randomised to abatacept who entered the long-term extension to receive ≥1 dose of abatacept, from year 1–2 (n=297)* and year 2–3 (n=295)†. Error bars represent the SEM.