Abatacept and Adalimumab show similar efficacy in early, seropositive rheumatoid arthritis patients with HLA-DRB1 shared epitope

For patients with rheumatoid arthritis (RA), especially those with early disease, an inadequate response to methotrexate (MTX-IR), and specific genetic markers like dual seropositivity for anticitrullinated protein antibodies (ACPAs) and rheumatoid factor (RF), plus the HLA-DRB1 shared epitope (SE), identifying optimal advanced therapies is crucial. These markers often indicate a more aggressive disease course. Current biologic disease-modifying antirheumatic drugs (bDMARDs) like TNF inhibitors and T-cell costimulation modulators offer significant benefits, but head-to-head comparisons in such specific high-risk populations are needed to guide treatment selection and improve patient outcomes.

The global, phase 3, single-blind AMPLIFIED trial (NCT04909801) randomized 338 patients with early RA, MTX-IR, and ACPA/RF/SE positivity to receive either abatacept or adalimumab at standard clinical doses. The primary endpoint was a 50% improvement in the American College of Rheumatology criteria (ACR50) at week 24 within the SE-positive subgroup. Exploratory analyses included biomarkers, immune cell subsets, and patient-reported outcomes (PROs) to assess broader treatment effects and safety profiles.

The primary endpoint was not met, indicating no statistically significant superior response for either treatment. ACR50 at week 24 was 59% for abatacept and 60% for adalimumab, with an adjusted odds ratio of 1.0 (95% CI: 0.6-1.6). Both treatments effectively reduced levels of anti-cyclic citrullinated peptide 2, C-reactive protein, and RF. Abatacept and adalimumab exhibited differential impacts on immune modulation, notably affecting B-cell homeostasis. Both biologics significantly improved PROs, including pain scores. Safety profiles were similar, with adverse event rates of 58.0% for abatacept and 59.2% for adalimumab, and serious adverse events at 2.4% vs 3.6%, respectively. Most patients (96%) completed the treatment period.

The AMPLIFIED trial demonstrated that abatacept and adalimumab offered comparable clinical efficacy and safety in this specific high-risk RA population.