Disease Remission, Normalized Physical Function and Radiographic Non-progression Are Achieved by the Majority of Patients with Early Rheumatoid Arthritis (RA) Treated with Abatacept (ABA) + Methotrexate (MTX): Results from the 2-year Agree Trial

OBJECTIVE: Evaluate clinical and radiographic outcomes with ABA + MTX over 2 yrs in MTX-naïve early RA patients. METHODS: The AGREE study had a 1-yr double-blind (DB) and 1-yr open-label (OL) period. Early RA patients with poor prognostic factors were randomized to ABA (~10 mg/kg) + MTX (therapy 1[T1]) or placebo + MTX (therapy 2[T2]) for the DB period; all patients received T1 during the OL period. Efficacy and safety were assessed for patients who received ≥1 dose of OL ABA. DAS28 (CRP], defined remission (DAS28 <2.6) and tender/swollen (active) joints (28-joint count) were assessed for the modified intent-to-treat population (dropouts=non-responders). Normalized HAQ-DI, score ≤0.5, was evaluated for patients with data available (as observed). Radiographic progression was assessed using Genant-modified Sharp scores (change in total score[TS]; non-progression=change from baseline in TS≤0 [as-observed data]). RESULTS: 459 patients (both arms) completed Yr 1 and continued in Yr 2; of those, 94.3% completed Yr 2. Mean baseline DAS28 (CRP) was 6.3; HAQ-DI 1.7; TS 7.5. The proportion of patients randomized to T1 achieving remission was maintained (46.1 vs 55.2% at Yrs 1 and 2). Of those in remission at Yr 2, the majority (63.5%) had 0 active joints; 11.9, 7.1 and 17.5% had 1, 2 and ≥3 active joints, respectively. For the T2, 26.9% achieved remission at Yr 1; after switching to T1, 44.5% achieved remission at Yr 2. The rate of HAQ-DI normalization was maintained over 2 yrs for the T1, with 49.1 and 54.7% at Yrs 1 and 2; rates for the T2 were 35.6% at Yr 1 and 47.6% at Yr 2 after addition of ABA. Patients randomized to T1 had significantly less structural damage progression in Yr 2 than in Yr 1 (mean change in TS: 0.65 from baseline to Yr 1 vs 0.18 from Yr 1–2; p<0.001). For patients randomized to T2, mean change in TS was 1.48 from baseline to Yr 1 vs 0.25 from Yr 1–2; p<0.001. Mean changes from baseline to Yr 2 was significantly lower for the original T1 vs those who switched at Yr 1; 0.84 vs 1.75, p=0.001. The rate of non-progression over 2 yrs was 56.8% in the T1 vs 43.8% in the T2; 91.1% of patients randomized to T1 who were non-progressors at Yr 1 remained non-progressors at Yr 2. Adverse events, including serious infections, malignancies and autoimmune events, during Yr 2 were consistent with those reported in Yr 11. CONCLUSION: Early introduction of T1 results in greater sustainable clinical and radiographic benefits and normalization of function in the majority of MTX-naïve early RA patients vs T2, supporting the use of T1 earlier in disease.