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

Area of Science:

• Rheumatology
• Immunology
• Clinical Trials

Background:

• Rheumatoid arthritis (RA) treatment aims for early sustained remission to minimize joint damage and disability.
• The study investigated abatacept plus methotrexate versus placebo plus methotrexate in early RA patients.

Purpose of the Study:

• To evaluate Simplified Disease Activity Index (SDAI) remission rates at 24 weeks with abatacept plus methotrexate.
• To assess the impact of de-escalation strategies on maintaining remission in anti-citrullinated protein antibody (ACPA)-positive patients.

Main Methods:

• Phase IIIb, randomized AVERT-2 study (NCT02504268) comparing weekly abatacept + methotrexate vs. placebo + methotrexate.
• SDAI remission (≤3.3) was the primary endpoint at week 24.
• Exploratory endpoint involved de-escalation strategies (tapering or withdrawing abatacept/methotrexate) in patients with sustained remission.

Main Results:

• The primary endpoint was not met: 21.3% achieved SDAI remission with combination therapy vs. 16.0% with placebo (p=0.2359).
• Numerical benefits for combination therapy were observed in clinical assessments, patient-reported outcomes (PROs), and radiographic non-progression.
• In patients with sustained remission, continued combination therapy maintained remission in 74%, compared to 48.0% with placebo and 57.4% with monotherapy.

Conclusions:

• The stringent primary endpoint for early remission was not achieved.
• In patients who achieved sustained remission, continuing abatacept plus methotrexate numerically maintained remission better than de-escalation or withdrawal strategies.
• De-escalating to every-other-week abatacept plus methotrexate preserved remission before drug withdrawal.