Evaluating drug-free remission with abatacept in early rheumatoid arthritis: results from the phase 3b, multicentre, randomised, active-controlled AVERT study of 24 months, with a 12-month, double-blind treatment period

Abstract

Objectives: To evaluate clinical remission with subcutaneous abatacept plus methotrexate (MTX) and abatacept monotherapy at 12 months in patients with early rheumatoid arthritis (RA), and maintenance of remission following the rapid withdrawal of all RA treatment.

Methods: In the Assessing Very Early Rheumatoid arthritis Treatment phase 3b trial, patients with early active RA were randomised to double-blind, weekly, subcutaneous abatacept 125 mg plus MTX, abatacept 125 mg monotherapy, or MTX for 12 months. Patients with low disease activity (Disease Activity Score (DAS)28 (C reactive protein (CRP)) <3.2) at month 12 entered a 12-month period of withdrawal of all RA therapy. The coprimary endpoints were the proportion of patients with DAS28 (CRP) <2.6 at month 12 and both months 12 and 18, for abatacept plus MTX versus MTX.

Results: Patients had <2 years of RA symptoms, DAS28 (CRP) ≥3.2, anticitrullinated peptide-2 antibody positivity and 95.2% were rheumatoid factor positive. For abatacept plus MTX versus MTX, DAS28 (CRP) <2.6 was achieved in 60.9% versus 45.2% (p=0.010) at 12 months, and following treatment withdrawal, in 14.8% versus 7.8% (p=0.045) at both 12 and 18 months. DAS28 (CRP) <2.6 was achieved for abatacept monotherapy in 42.5% (month 12) and 12.4% (both months 12 and 18). Both abatacept arms had a safety profile comparable with MTX alone.

Conclusions: Abatacept plus MTX demonstrated robust efficacy compared with MTX alone in early RA, with a good safety profile. The achievement of sustained remission following withdrawal of all RA therapy suggests an effect of abatacept's mechanism on autoimmune processes.

Trial registration number: NCT01142726.

Keywords: DMARDs (biological); Disease Activity; Methotrexate; Rheumatoid Arthritis.

Figure 1

Efficacy outcomes over time. (A) proportion of patients with DAS-defined remission (DAS28 (CRP) <2.6); (B) proportion of patients with SDAI remission (≤3.3); (C) proportion of patients with Boolean remission (tender joint count ≤1, swollen joint count ≤1, patient global assessment of disease activity ≤1 (0–10 scale), high-sensitivity CRP ≤1 mg/dL); (D) major clinical response (ACR 70 response for a minimum of six consecutive months at any time period prior to the time point). Error bars represent 95% CIs. Missing remission data not due to premature discontinuation and not at day 1 of the treatment period or at day 169 of the withdrawal period were imputed as a remission if the missing value occurred between two observed remissions. Missing ACR response data not due to premature discontinuation and not at day 1 of the treatment period or at day 169 of the withdrawal period were imputed as an ACR response if the missing value occurred between two observed ACR responses. ACR, American College of Rheumatology; CRP, C reactive protein; DAS, Disease Activity Score; MTX, methotrexate; SDAI, Simplified Disease Activity Index.

Figure 2

Proportion of patients in Disease Activity Score (DAS)-defined remission (DAS28 (C reactive protein, CRP) <2.6) during the withdrawal period. The numbers within the bars are percentages. Missing remission data not due to premature discontinuation and not at day 1 of the treatment period or at day 169 of the withdrawal period were imputed as a remission if the missing value occurred between two observed remissions. MTX, methotrexate.