A randomized, double-blind, placebo-controlled trial of abatacept for the treatment of relapsing, non-severe, granulomatosis with polyangiitis.

Objective: To compare the efficacy of abatacept to placebo for the treatment of relapsing, non-severe granulomatosis with polyangiitis (GPA).

Methods: In this multicenter trial, eligible patients with relapsing, non-severe GPA were randomized to receive abatacept 125 mg subcutaneously once a week or placebo, both together with prednisone 30 mg/day (or equivalent), tapered and discontinued at week 12. Patients already taking methotrexate, azathioprine, mycophenolate, or leflunomide continued this medication at a stable dose. Patients achieving remission remained on their randomized assignment until relapse, early termination, or the common close date 12 months after enrollment of the last patient. Those who had a non-severe relapse, non-severe worsening, or were not in remission by month 6 had the option to receive open-label abatacept. The primary endpoint was the rate of treatment failure, defined as relapse, disease worsening, or failure to achieve a BVAS/WG=0 or 1 by 6 months.

Results: Sixty-five patients were randomized, 34 received abatacept and 31 placebo. No statistical difference in the treatment failure rate was found between those who received abatacept compared to placebo (p= 0.853). Treatment with abatacept did not demonstrate any statistical difference from placebo in key secondary endpoints, including time to full remission (BVAS/WG=0), duration of glucocorticoid-free remission, relapse severity, prevention of damage, or patient-reported quality-of life outcomes. There was no difference in the frequency or severity of adverse events between treatment arms, including infection.

Conclusions: In patients with relapsing, non-severe GPA abatacept did not reduce the risk of relapse, severe worsening, or failure to achieve remission.