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Journal article from the Cleveland Clinic Journal of Medicine

Treating Vasculitis with Conventional
Immunosuppressive Agents

David Jayne, MD, FRCP

Dr. Jayne reported that he has received research grant support from Roche/Genentech and Vifor Pharma. This article was developed from an audio transcript of Dr. Jayne’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. Jayne.



Standard therapy for granulomatosis with polyangiitis (Wegener granulomatosis) and other vasculitides is a combination of cyclophosphamide and glucocorticoids. Although most patients achieve remission, relapses and treatment-related morbidities are common. Clinical trials have yielded a wealth of data about less toxic alternatives to standard therapy, including new agents and methods of delivery. All aim to reduce long-term exposure to cyclophosphamide and glucocorticoids and so maintain safety while effectively preventing relapse. Individualized evaluation of  risk and treatment selection will help maximize effectiveness and minimize toxicity.

In 1958, shortly after the first descriptions of granulomatosis with polyangiitis, or GPA (Wegener’s granulomatosis ), the 1-year mortality was 18%,(1) mainly due to renal failure. Physicians tried to combat the disease using various immunosuppressive drugs (nitrogen mustard and, in later years, azathioprine and methotrexate), but measurable success came only after investigators introduced cyclophosphamide (CYC) in combination with the glucocorticoid prednisone.(2)

A key 1992 study showed that the CYC/prednisone combination markedly improved the disease status in 91% of patients,(3) with 75% achieving complete remission. The treatment came at a price, however, with almost all patients suffering serious morbidity or side effects. The results also highlighted concerns about potential malignancies caused by prolonged use of CYC and glucocorticoids. Those concerns motivated the European Vasculitis Study Group in the late 1980s and early 1990s to design and validate testing for antineutrophil cytoplasmic antibody (ANCA)–associated vasculitides (AAV) and pursue consensus regarding treatment.(4)