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Journal article from the Cleveland Clinic Journal of Medicine

Biologic Agents in the Treatment
of Granulomatosis with Polyangiitis

Ulrich Specks, MD

Professor of Medicine, Division of Pulmonary and Critical Care Medicine, Mayo Clinic College of Medicine, Rochester, MN

Dr. Specks reported that he has received consulting fees from Dynavax and Sanofi-Aventis.
This article was developed from an audio transcript of Dr. Specks’s presentation at the “New Directions in Small-Vessel Vasculitis—ANCA, Target Organs, Treatment, and Beyond” symposium held at Cleveland Clinic on May 4, 2011. The transcript was formatted and edited by Cleveland Clinic Journal of Medicine staff for clarity and conciseness, and was then reviewed, revised, and approved by Dr. Specks.

Acknowledgment. Genentech provided drug and funding to the National Institute of Allergy and Infectious Disease for the conduct of the Rituximab in ANCA-Associated Vasculitis (RAVE) trial.



Granulomatosis with polyangiitis (GPA) is a type of vasculitis that affects the respiratory tract and kidneys. Without treatment, half of patients die within 6 months. Standard therapy (a daily combination of cyclophosphamide and glucocorticoids) can induce remission, but the duration is short and treatment is plagued by serious morbidity. Advances in understanding the potential target of cyclophosphamide— B cells, that indirectly give rise to antineutrophil cytoplasmic antibodies (ANCA)—led to a new B-cell–targeted strategy. We administered rituximab, an anti–B-cell agent, to patients with severe GPA and microscopic polyangiitis. Overall, rituximab matched the efficacy of cyclophosphamide in inducing remission and was superior in patients with relapsing disease. The timing of re-treatment can be individualized based on patients’ B-cell counts and ANCA levels in patients with chronically relapsing GPA.

Granulomatosis with polyangiitis (GPA [Wegener’s granulomatosis]) is a vasculitis that affects the renal and respiratory systems. Remission can be induced in most patients with the combination of glucocorticoids and cyclophosphamide. Unfortunately, patients often suffer disease relapses requiring re-treatment and exposure to the cumulative toxicities of repeated cyclophosphamide use. In recent years, improved understanding of the mechanisms of action of cyclophosphamide has led to investigation of treatment strategies that target the role of B cells more specifically in the pathogenesis of the disease.

This article reviews the results of recent studies involving the use of biologic therapy in the treatment of GPA, with a brief examination of historic events that influenced the design of recent trials.