Sustained Remission and Outcomes with Abatacept plus Methotrexate Following Stepwise Dose De-escalation in Patients with Early Rheumatoid Arthritis

• Published in: Rheumatology and therapy. 2023-06, Vol.10 (3), p.707-727
• Main Authors: Emery, Paul, Tanaka, Yoshiya, Bykerk, Vivian P., Huizinga, Thomas W. J., Citera, Gustavo, Bingham, Clifton O., Banerjee, Subhashis, Soule, Benjamin P., Nys, Marleen, Connolly, Sean E., Lozenski, Karissa L., Zhuo, Joe, Wong, Robert, Huang, Kuan-Hsiang Gary, Fleischmann, Roy
• Format: Article
• Language: English
• Subjects: Abatacept; Anti-citrullinated protein autoantibodies (ACPAs); Clinical trial; Disease-modifying antirheumatic drugs (DMARDs); Family Medicine; General Practice; Internal Medicine; Medicine; Medicine & Public Health; NCT; NCT02504268; Original Research; Orthopedics; Patients; Proteins; Quality of Life Research; Remission (Medicine); Rheumatoid arthritis; Rheumatology
• ISSN: 2198-6576; 2198-6584
• DOI: 10.1007/s40744-022-00519-9

Introduction One target of rheumatoid arthritis (RA) treatment is to achieve early sustained remission; over the long term, patients in sustained remission have less structural joint damage and physical disability. We evaluated Simplified Disease Activity Index (SDAI) remission with abatacept + methotrexate versus abatacept placebo + methotrexate and impact of de-escalation (DE) in anti-citrullinated protein antibody (ACPA)-positive patients with early RA. Methods The phase IIIb, randomized, AVERT-2 two-stage study (NCT02504268) evaluated weekly abatacept + methotrexate versus abatacept placebo + methotrexate. Primary endpoint: SDAI remission (≤ 3.3) at week 24. Pre-planned exploratory endpoint: maintenance of remission in patients with sustained remission (weeks 40 and 52) who, from week 56 for 48 weeks (DE period), (1) continued combination abatacept + methotrexate, (2) tapered abatacept to every other week (EOW) + methotrexate for 24 weeks with subsequent abatacept withdrawal (abatacept placebo + methotrexate), or (3) withdrew methotrexate (abatacept monotherapy). Results Primary study endpoint was not met: 21.3% (48/225) of patients in the combination and 16.0% (24/150) in the abatacept placebo + methotrexate arm achieved SDAI remission at week 24 ( p  = 0.2359). There were numerical differences favoring combination therapy in clinical assessments, patient-reported outcomes (PROs) and week 52 radiographic non-progression. After week 56, 147 patients in sustained remission with abatacept + methotrexate were randomized (combination, n  = 50; DE/withdrawal, n  = 50; abatacept monotherapy, n  = 47) and entered DE. At DE week 48, SDAI remission (74%) and PRO improvements were mostly maintained with continued combination therapy; lower remission rates were observed with abatacept placebo + methotrexate (48.0%) and with abatacept monotherapy (57.4%). Before withdrawal, de-escalating to abatacept EOW + methotrexate preserved remission. Conclusions The stringent primary endpoint was not met. However, in patients achieving sustained SDAI remission, numerically more maintained remission with continued abatacept + methotrexate versus abatacept monotherapy or withdrawal. Trial Registration ClinicalTrials.gov identifier, NCT02504268. 6DHXqidsCNRrz-f8FYdsgJ Video abstract (MP4 62241 KB) Plain Language Summary Patients with rheumatoid arthritis (RA) experience inflamed and damaged joints. RA is an autoimmune disease in which proteins called autoantibodies, particularl