Clinical trials in antineutrophil cytoplasmic antibody-associated vasculitis: what we have learnt so far, and what we still have to learn

The prognosis of the antineutrophil cytoplasmic antibody associated vasculitides (AAV), microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA) and eosinophilic GPA (EGPA), has been fundamentally improved over the last five decades by the use of glucocorticoids and immunosuppressants, turning them from consistently fatal diseases into chronic conditions. The long-term course is now largely determined by the frequency of disease flares and by accruing damage caused by disease activity and treatment-related comorbidities. This review summarizes the evidence derived from clinical trials performed during the last 30 years and the remaining clinical unmet needs that new studies aim to address. In MPA and GPA, ongoing studies assess (i) different strategies to reduce cumulative glucocorticoid doses currently used for induction and maintenance of remission, (ii) the efficacy of new drugs and (iii) the optimal duration of immunosuppression and the use of biomarkers to individualize therapy. Prospective randomized trials also target disease-associated cardiovascular risk and infections. The first prospective controlled trials specifically designed for EGPA have recently been launched and could lead to new therapeutic options for patients diagnosed with this rare disease. This is an exciting time for researchers in the field of AAV, and for patients as collaborative efforts raise the hope of developing new therapies and more individualized approaches to the management of the diseases, maximizing efficacy while minimizing treatment toxicities.