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. Video abstract (MP4 62241 KB).
Keywords: Abatacept; Anti-citrullinated protein autoantibodies (ACPAs); Clinical trial; Disease-modifying antirheumatic drugs (DMARDs); Rheumatoid arthritis.
Patients with rheumatoid arthritis (RA) experience inflamed and damaged joints. RA is an autoimmune disease in which proteins called autoantibodies, particularly anti-citrullinated protein autoantibodies, target the patient’s own joint tissue and organs by mistake, leading to symptomatic inflammation. Successful treatment can decrease the disease’s activity to a state known as remission. Patients in remission may experience little or no symptoms and it may be possible for some to then be able to decrease their treatment. Here, we report the results of a large, international study that looked at two treatments, abatacept and methotrexate, in patients with RA and anti-citrullinated protein autoantibodies. The study had two parts. Firstly, to see how many patients had success (remission) with weekly abatacept and/or methotrexate treatment, and secondly, to see if remission was maintained when treatment was either continued or decreased and stopped. The study showed that the number of patients in remission 6 months after treatment started was not greatly different between patients treated with both abatacept and methotrexate and those treated with just methotrexate. Those taking abatacept and methotrexate together had better remission rates 1 year later. More patients also stayed in remission when they continued to receive both abatacept and methotrexate compared with those who were just treated with abatacept or when their abatacept treatment was decreased and stopped. More patients stayed in remission when abatacept was decreased than when it was stopped. The results from this study may help determine possible future treatment reduction and/or withdrawal plans for some patients with RA.
© 2023. The Author(s).