Background/Purpose: Granulomatosis with polyangiitis (Wegener’s, GPA) is a primary systemic vasculitis that carries a high predilection for relapse. An area of unmet need has been treatment options for patients with mild relapsing GPA, many of whom require long-term glucocorticoids. T-cell activation has been implicated in the pathophysiology of GPA. We conducted an open-label trial to examine the safety and efficacy of abatacept (CTLA4-Ig) in patients with mild relapsing GPA.

Methods: Standardized definitions were used to identify patients with mild relapsing GPA. 20 patients were treated with abatacept 10mg/kg IV days 1, 15, 29 and monthly thereafter. Patients on methotrexate (MTX), azathioprine (AZA), or mycophenolate mofetil (MMF) at enrollment continued these agents without dosage increase. Prednisone ≤ 30 mg daily was permitted at entry, but the dose had to be tapered down to the pre-relapse dose by month 2. Safety and efficacy data were collected at each infusion, disease activity was assessed by the BVAS/WG, damage was assessed by the Vasculitis Damage Index (VDI). Patients received abatacept until meeting criteria for early termination or until the common closeout date of 6 months after enrollment of the last patient.

Results: Disease characteristics of the 20 enrolled patients are outlined in the Table.

Of the 20 patients, 14 (70%) were on either MTX (N=7), AZA (N=3), or MMF (N=4). 14 patients had taken prednisone during the 12 months prior to enrollment, 13 were on at the time of enrollment, and 15 (75%) received prednisone during the first 2 months of study treatment. The maximum prednisone doses were 30 mg (N=3), 20 mg (N=3), 12-15 mg (N=2), 10 mg (N=4), 7.5 mg (N=1), 5 mg (N=2) with only 5 having a dose increase at trial entry. During the study, 11 of the 15 patients on prednisone reached a dose of 0 mg. 10 of the 14 patients who had been on long-term prednisone were able to discontinue prednisone and 7 of these remained off the drug until common closing. Of the 20 patients, 18 (90%) had disease improvement, 16 (80%) achieved remission (BVAS/WG=0) at a median of 3.75 months (range 1-19), and 14 (70%) reached common closing. 6 (30%) met criteria for early termination due to increased disease activity but none had severe disease; 3 of 6 achieved remission and relapsed at a median of 8.33 months (range 6-10). The median duration of remission before common closing was 12 months (range 4-21). 9 serious adverse events occurred in 7 patients, including 7 infections that were successfully treated.

Conclusion : In this population of patients with mild relapsing GPA, abatacept was well tolerated and was associated with disease remission and discontinuation of prednisone in a high percentage of patients. These findings suggest that abatacept warrants further study as a possible treatment option for patients who have non-severe, relapsing GPA.