By Carol A. Langford, MD, MHS
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An exciting new study in granulomatosis with polyangiitis (Wegener’s) (GPA) has begun: The first sites in the Abatacept (CTLA4-Ig) for the Treatment of Relapsing, Non-Severe GPA (ABROGATE) trial recently opened to enrollment, with more to join later this year. This trial will be a multinational initiative conducted by the Vasculitis Clinical Research Consortium (VCRC) in partnership with the European Vasculitis Study Group (EUVAS) and other international collaborators.
An unmet need: Treatment of nonsevere GPA
By focusing on a treatment option for the management of nonsevere GPA, ABROGATE addresses an unmet therapeutic need. Despite advances in the treatment of GPA, 50 to 70 percent of patients continue to experience a disease relapse following successful remission induction. For many patients, nonsevere relapses can greatly impact quality of life through accrued organ damage and the need for chronic glucocorticoids. The identification of a therapeutic strategy to safely and effectively reduce nonsevere relapses would represent an important addition to the treatment armamentarium in GPA.
Building on an encouraging pilot study
ABROGATE follows up on the promising results seen in the VCRC pilot study of abatacept in 20 patients with nonsevere relapsing GPA that was funded by the National Institutes of Health.
In this pilot study — which was published in Annals of the Rheumatic Diseases and profiled in a previous Consult QD post — all patients received intravenous abatacept 10 mg/kg on days 1, 15 and 29 and every four weeks thereafter. Prednisone up to 30 mg daily was allowed within the first two months, and patients on methotrexate, azathioprine or mycophenolate mofetil at enrollment continued these agents without dosage increase. Patients remained on study until meeting criteria for early termination or until common closing, which was six months after enrollment of the final participant.
Of the 20 patients, 18 (90 percent) had disease improvement, 16 (80 percent) achieved remission (defined as a Birmingham Vasculitis Activity Score for Wegener’s granulomatosis [BVAS/WG] of 0) and 14 (70 percent) reached the study common closing date. During the study, 11 of the 15 patients on prednisone (73 percent) reached 0 mg.
The findings from this pilot study demonstrated that in these 20 patients with nonsevere relapsing GPA, abatacept was well tolerated and associated with a high frequency of disease remission and prednisone discontinuation. While this experience remains insufficient to recommend the use of abatacept for GPA in clinical practice, it supported pursuit of a randomized trial to more definitively determine treatment efficacy.
The essentials of ABROGATE
ABROGATE will enroll 150 patients with nonsevere relapsing GPA. Eligible patients will be randomized to subcutaneous abatacept or placebo and will receive standardized glucocorticoids with continuation of their maintenance immunosuppressive agent (methotrexate, azathioprine, mycophenolate or leflunomide). Patients who experience nonsevere disease worsening or relapse, or who do not achieve remission by month 6, will have the option while on study of receiving abatacept through an open-label extension period.
One in a suite of GPA studies
The ABROGATE trial joins other ongoing VCRC clinical trials in GPA, including:
- An International, Open Label, Randomized Controlled Trial Comparing Rituximab with Azathioprine as Maintenance Therapy in Relapsing ANCA-Associated Vasculitis (RITAZAREM)
- Plasma Exchange and Glucocorticoid Dosing In ANCA-Associated Vasculitis (PEXIVAS)
- The Assessment of Prednisone in Remission Trial (TAPIR)
Further information about these studies can be located at clinicaltrials.gov or on the VCRC website. Physicians with questions about these studies or who wish to refer a patient for them should contact Dr. Langford.
Dr. Langford is Director of the Center for Vasculitis Care and Research as well as Vice Chair for Research, Department of Rheumatic and Immunologic Diseases.