A head-to-head comparison of abatacept and adalimumab in adults with early and dual seropositive rheumatoid arthritis plus HLA-DRB1 shared epitope: results from the randomised phase 3 AMPLIFIED trial.

Abstract

To determine if patients with early rheumatoid arthritis (RA), an inadequate response to methotrexate (MTX-IR), dual seropositivity for anticitrullinated protein antibodies (ACPAs) and rheumatoid factor (RF), plus shared epitope (SE) human leukocyte antigen risk allele would show a superior response to abatacept vs adalimumab. The AMPLIFIED trial (NCT04909801) was a global, phase 3, head-to-head, randomised, single-blind study designed to evaluate treatment response with abatacept vs adalimumab in patients with early RA and MTX-IR, with ACPA, RF, and SE positivity. The primary endpoint was a 50% improvement in the American College of Rheumatology criteria (ACR50) at week 24 in the SE-positive subgroup. Exploratory analyses included biomarkers, immune cell subsets, and patient-reported outcomes (PROs). In all, 338 patients were randomised. Most patients (96%) completed treatment. Baseline demographics, disease characteristics, and glucocorticoid use were balanced between arms. The primary endpoint was not met. ACR50 at week 24 was 59% with abatacept and 60% with adalimumab (adjusted odds ratio [95% CI]: 1.0 [0.6-1.6]). Levels of anti-cyclic citrullinated peptide 2, C-reactive protein, and RF decreased with both treatments. Abatacept and adalimumab had differential impacts on immune modulation, including B-cell homeostasis. Both treatments improved PROs, including pain. Abatacept and adalimumab demonstrated similar rates of adverse events (AEs; 58.0% vs 59.2%) and serious AEs (2.4% vs 3.6%). Patients responded well to both treatments, with no clear advantage of abatacept vs adalimumab. Most patients tolerated their assigned therapies.