Background/Purpose: Granulomatosis with polyangiitis (GPA) is a small-vessel vasculitis associated with frequent relapses. Following encouraging results from an open-label study, a randomized, double-blind, placebo-controlled trial was conducted at 22 sites to examine the efficacy and safety of abatacept combined with glucocorticoids for the treatment of relapsing, non-severe GPA.

Methods: Patients with relapsing, non-severe GPA were randomized to abatacept 125 mg SC once a week or placebo both combined with prednisone 30 mg/day (or equivalent) tapered and discontinued at week 12. Those already receiving methotrexate, azathioprine, mycophenolate, or leflunomide at enrollment continued this medication at a stable dose. Patients achieving remission remained on their randomized assignment until relapse, early termination, or the common close date that was 12 months after enrollment of the last patient. The primary endpoint was the rate of treatment failure, defined as a relapse, disease worsening, or failure to achieve BVAS/WG = 0 or 1. The study was designed to achieve 80% power at a 0.05 one-sided significance level to detect a 40% reduction in the expected failure rate for the abatacept arm as compared to the placebo arm.

Results: 65 eligible patients were randomized, 34 received abatacept and 31 received placebo. There was no difference in the baseline demographic and disease characteristics between arms (Table 1). The study population consisted of patients with longstanding, relapsing disease who had a history of receiving a range of immunosuppressive agents in the past, including 28 (43%) patients previously treated with rituximab.

During the trial, relapse or disease worsening occurred in 21 (62%) patients randomized to abatacept and 21 (68%) patients randomized to placebo. These outcomes included episodes of severe disease in 3 patients who received abatacept and 5 who received placebo. For the primary endpoint, no statistical difference in the treatment failure rate was found between those who received abatacept compared to placebo (P = 0.255), Figure 1. 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. 69 adverse events occurred in 36 patients, including 27 serious adverse events in 19 patients. There was no difference in the frequency or severity of adverse events between treatment arms, including the rate of infection.

Conclusion: In patients with relapsing, non-severe GPA the addition of abatacept to glucocorticoids did not reduce the risk of relapse, severe worsening, or failure to achieve remission. Treatment with abatacept was not associated with increased toxicity beyond glucocorticoids alone. Patients with relapsing, non-severe GPA represent a unique population with challenging unmet needs to better control disease activity. Further research is needed to understand pathophysiologic mechanisms and investigate novel treatment approaches for this subset of patients with GPA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-randomized-double-blind-placebo-controlled-trial-of-abatacept-for-the-treatment-of-relapsing-non-severe-granulomatosis-with-polyangiitis/