Immunotherapy in Eosinophilic Granulomatosis with Polyangiitis

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides include granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss). EGPA has distinct features, namely asthma, common rhino-sinusal involvement, hypereosinophilia, tissue infiltration with eosinophils and necrotizing granulomatosis vasculitis.Conventional immunosuppressive therapy and glucocorticoids have been GPA and MPA standard of care for remission induction and maintenance for four decades. This regimen hastransformed the outcome from death to a strong likelihood of disease controland temporary remission. However, most patients have recurrent relapses that lead to damage and require repeated treatment. Cumulative side effects of immunosuppressive agents and glucocorticoids thus remain major causes of long-term morbidity, damage and death.

The development of therapeutic immunomodulation in systemic autoimmune diseases has shed new light on these complex diseases. Rituximab, an anti-CD20 monoclonal antibody that depletes Bcells in peripheral blood, has been shown to be not inferior to cyclophosphamide to induce remission in GPA and MPA patients, with an acceptable safety profile, leading to its registration by the EMA and FDA as drug remission-induction therapy in these patients. In addition the MAINRITSAN trial, conducted by the French Vasculitis Study Group, demonstrated that pre-emptive low dose rituximab given every 6 months for 18 months was significantly more effective than azathioprine standard of care to maintain remission in GPA and MPA, with a similar profile of tolerance. Such therapeutic immunomodulation has changed the standard of care for maintenance therapy in these vasculitides. Read more...........