Subcutaneous Abatacept vs Adalimumab Head-to-head Comparison in Adults with Early, Dual Seropositive Rheumatoid Arthritis, Positive for the Shared Epitope HLA Class II Risk Alleles, and an Inadequate Response to Methotrexate: Results from a Phase 3 Trial
Speaker: Dr. Michael Weinblatt – Brigham and Women's Hospital & Harvard Medical School
Key Highlights:
This Phase 3 trial evaluated the efficacy and safety of subcutaneous Abatacept (ABBA) versus Adalimumab (ADA) in adults with early, dual-seropositive rheumatoid arthritis (RA) who exhibited an inadequate response to methotrexate (MTX). Participants were positive for anti-cyclic citrullinated peptide (CCP) antibodies and rheumatoid factor (RF) and predominantly shared the HLA class II shared epitope (SE).
The trial aimed to explore whether Abatacept offers superior outcomes in this high-risk population.
Study Design and Baseline Characteristics:
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Trial Type: Single-blind, multicentred, global.
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Inclusion Criteria:
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Incomplete responders on methotrexate with active disease.
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Disease duration: Less than 12 months (early rheumatoid arthritis).
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At least 3 tender or swollen joints.
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DAS CRP greater than 3.2.
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Dual-positive for CCP (greater than 3 times the upper limit of normal) and rheumatoid factor.
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Must have been on methotrexate for at least 3 months with active disease.
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Naive to targeted biologics and targeted synthetic therapies (e.g., JAK inhibitors).
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Population: 338 adults with RA of ≤12 months' duration; 65% were SE-positive.
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Treatment: All participants received background MTX and were randomized to ABBA (125 mg QW, N = 169) or ADA (40 mg Q2W, N = 169) arms. In each arm, there were 132 patients who completed the treatment period.
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Endpoints:
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Primary: ACR50 response at 24 weeks in SE-positive patients.
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Secondary: Patient-reported outcomes (PROs), including pain, fatigue, quality of life (QoL), and work productivity.
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Patients had active disease at baseline, with mean Disease Activity Score (DAS-CRP) of 5.2 and RF/anti-CCP titres significantly elevated.
Key Findings:
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Primary Endpoint: ACR50 at week 24 in SE+ patients: Similar efficacy was observed (ABBA: 59%, ADA: 60.3%), with no statistically significant difference between groups. The study failed to meet the primary endpoint.
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Kinetics of response were similar across ACR20, ACR50, and ACR70 endpoints, supporting earlier observations.
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The response curves are identical to those reported in the early RA trial, showing that both ABBA and Adalimumab demonstrated efficacy by 4 weeks, with their response lines overlapping throughout the 24-week study duration.
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Patient-Reported Outcomes:
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Comparable improvements in pain, fatigue, morning stiffness, and health-related QoL (assessed by SF-36).
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Both drugs showed significant enhancements in work productivity and activity, without a clear advantage for ABBA.
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Serological Markers: ABBA was associated with greater reductions in RF and CCP titres than ADA, although CRP decreases were similar.
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Safety:
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Both treatments were well-tolerated. Serious adverse events (SAEs) occurred in 1% of patients on ABBA vs. 2% on ADA.
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No deaths were reported, and COVID-19 infections during the trial were non-serious.
Conclusion:
In conclusion, both abatacept (ABBA) and adalimumab (ADA) are highly effective in treating early rheumatoid arthritis (RA), including in high-risk populations with dual seropositivity and SE positivity. Unlike previous studies, such as the early AMPL trial, this study did not find a superior response for ABBA in SE-positive patients, possibly due to differences in patient populations and geographical variations. The results emphasize the critical role of early diagnosis and timely initiation of treatment in achieving optimal outcomes for RA patients. Additionally, the study demonstrates the equivalence of ABBA and ADA in combination with methotrexate, confirming the efficacy of both drugs in managing early RA.
American College of Rheumatology Convergence 2024, November 14–19, Washington, D.C.
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