Treatment of cyclophosphamide-resistant granulomatosis with polyangiitis (Wegener's) and microscopic polyangiitis
- Ronald J Falk, MD
Ronald J Falk, MD
- Professor and Nephrology Division Chief
- University of North Carolina at Chapel Hill
- Section Editors
- Richard J Glassock, MD, MACP
Richard J Glassock, MD, MACP
- Editor-in-Chief — Nephrology
- Section Editor — Glomerular Diseases
- Emeritus Professor
- The David Geffen School of Medicine at UCLA
- Gerald B Appel, MD
Gerald B Appel, MD
- Section Editor — Glomerular Diseases
- Professor of Medicine
- Columbia University College of Physicians and Surgeons
In January 2011, the Boards of Directors of the American College of Rheumatology, the American Society of Nephrology, and the European League Against Rheumatism recommended that the name Wegener's granulomatosis be changed to granulomatosis with polyangiitis (Wegener's), abbreviated as GPA [1-3]. This change reflects a plan to gradually shift from honorific eponyms to a disease-descriptive or etiology-based nomenclature. The parenthetic reference to Wegener's will be phased out after several years as the new name becomes more widely known
Granulomatosis with polyangiitis (Wegener's), which can be abbreviated as GPA, and microscopic polyangiitis (MPA) are related systemic vasculitides. Both are associated with antineutrophil cytoplasmic antibodies (ANCA), have similar features on renal histology (eg, a focal necrotizing, pauci-immune, crescentic glomerulonephritis), and have similar outcomes. There are, however, several differences between these disorders. (See "Clinical manifestations and diagnosis of granulomatosis with polyangiitis (Wegener's) and microscopic polyangiitis", section on 'Clinical presentation'.)
For patients with life-threatening or organ-threatening disease, cyclophosphamide in combination with glucocorticoids is the standard of care for initial immunosuppressive therapy, although two randomized trials with limited follow-up have shown that rituximab was as effective as cyclophosphamide in inducing remission of patients with newly diagnosed or relapsing GPA or MPA [4,5].
The treatment of cyclophosphamide-resistant GPA or MPA will be reviewed here. Initial and maintenance immunosuppressive therapy, the clinical manifestations and diagnosis of these diseases, the treatment of relapsing disease, and patient and renal outcomes are discussed elsewhere. (See "Initial immunosuppressive therapy in granulomatosis with polyangiitis and microscopic polyangiitis" and "Maintenance immunosuppressive therapy in granulomatosis with polyangiitis and microscopic polyangiitis" and "Clinical manifestations and diagnosis of granulomatosis with polyangiitis (Wegener's) and microscopic polyangiitis" and "Identification and management of relapsing disease in granulomatosis with polyangiitis and microscopic polyangiitis" and "Prognosis in granulomatosis with polyangiitis and microscopic polyangiitis, and management of those who develop end-stage renal disease".)
True cyclophosphamide resistance in granulomatosis with polyangiitis (Wegener's), abbreviated as GPA, and MPA is defined as the presence of active disease affecting a major organ despite optimal initial immunosuppressive therapy with cyclophosphamide and glucocorticoids. (See "Initial immunosuppressive therapy in granulomatosis with polyangiitis and microscopic polyangiitis".)
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- NEW TERMINOLOGY
- Cannot take cyclophosphamide
- Unresponsive but not resistant
- INCIDENCE AND RISK FACTORS
- TREATMENT OF CYCLOPHOSPHAMIDE-RESISTANT DISEASE
- Possibly effective therapies
- - Rituximab
- - Mycophenolate mofetil
- Therapies of unproven efficacy
- - Anti-TNF-alpha therapy
- - Anti-T cell antibodies
- - Intravenous immune globulin
- - Intravenous azathioprine
- - 15-Deoxyspergualin
- - Radiation therapy
- - Stem cell transplantation
- SUMMARY AND RECOMMENDATIONS