Head-to-head comparison of subcutaneous abatacept versus adalimumab for rheumatoid arthritis: two-year efficacy and safety findings from AMPLE trial

Abstract

Objectives: To compare over 2 years the safety, efficacy and radiographic outcomes of subcutaneous abatacept versus adalimumab, in combination with methotrexate (MTX), in patients with rheumatoid arthritis (RA).

Methods: AMPLE is a phase IIIb, 2-year, randomised, investigator-blinded study with a 1-year primary endpoint. Biologic-naive patients with active RA and an inadequate response to MTX were randomised to 125 mg abatacept weekly or 40 mg adalimumab bi-weekly, both with a stable dose of MTX.

Results: Of 646 patients randomised, 79.2% abatacept and 74.7% adalimumab patients completed year 2. At year 2, efficacy outcomes, including radiographic, remained comparable between groups and with year 1 results. The American College Rheumatology 20, 50 and 70 responses at year 2 were 59.7%, 44.7% and 31.1% for abatacept and 60.1%, 46.6% and 29.3% for adalimumab. There were similar rates of adverse events (AEs) and serious adverse events (SAEs). More serious infections occurred with adalimumab (3.8% vs 5.8%) including two cases of tuberculosis with adalimumab. There were fewer discontinuations due to AEs (3.8% vs 9.5%), SAEs (1.6% vs 4.9%) and serious infections (0/12 vs 9/19 patients) in the abatacept group. Injection site reactions (ISRs) occurred less frequently with abatacept (4.1% vs 10.4%).

Conclusions: Through 2 years of blinded treatment in this first head-to-head study between biologic disease-modifying antirheumatic drugs in RA patients with an inadequate response to MTX, subcutaneous abatacept and adalimumab were similarly efficacious based on clinical, functional and radiographic outcomes. Overall, AE frequency was similar in both groups but there were less discontinuations due to AEs, SAEs, serious infections and fewer local ISRs with abatacept.

Trial registration: ClinicalTrials.gov NCT00929864.

Keywords: DMARDs (Biologic); Methotrexate; Rheumatoid Arthritis.

Figure 1

Disposition of patients over 2 years in the intent-to-treat population randomised to subcutaneous (SC) abatacept or adalimumab, both given in combination with methotrexate (MTX).

Figure 2

Proportions of patients meeting efficacy endpoints in the subcutaneous (SC) abatacept or adalimumab treatment groups over 2 years. (A) Rates of American College Rheumatology (ACR) responses for the intent-to-treat population (N=318 in the SC abatacept-treated group, and N=328 in the adalimumab-treated group). Error bars represent 95% CIs. (B) Disease Activity Score in 28 joints using the C reactive protein level (DAS28-CRP). Data represent mean DAS28-CRP over 2 years. (C) The proportions of SC abatacept- or adalimumab-treated patients who demonstrated the Health Assessment Questionnaire–Disability Index (HAQ-DI) response (improvement of ≥0.3 units from baseline) over 2 years. Error bars represent 95% CIs. Efficacy outcomes through year 1 have been reported earlier.

Figure 3

The seven components of the American College of Rheumatology core set of outcome measures were assessed in patients treated with subcutaneous (SC) abatacept or adalimumab over 2 years. Data shown here are adjusted mean change from baseline to 2 years. C reactive protein data shown here are absolute mean values through 2 years. Adjustment based on ANCOVA model with treatment as factor and baseline values, Disease Activity Score in 28 joints using the C reactive protein level (DAS28-CRP) stratification as covariates.

Figure 4

Radiographic outcomes in patients treated with subcutaneous (SC) abatacept or adalimumab over 2 years. The cumulative probability plot shows the distribution of change in modified total Sharp/van der Heijde scores of radiographic damage from baseline to 2 years by treatment group.