The prior 2009 EULAR recommendations were very much in need of updating given the plethora of studies in the past 7 years addressing ANCA-associated vasculitis (AAV). The emergence of rituximab as an effective therapy in AAV had to be considered and included in these newer guidelines. Its potential role in both remission induction, as well as remission maintenance of AAV, is addressed.
The recommendations are somewhat complicated, particularly as eosinophilic granulomatosis with polyangiitis (EGPA, previously referred to as Churg-Strauss syndrome) has been included, but most of the well-done prospective clinical trials addressing remission induction and remission maintenance in AAV were limited to patients with granulomatosis with polyangiitis or microscopic polyangiitis and did not include patients with EGPA. The role of plasma exchange is also discussed, but the results of the PEXIVAS trial, which will address that more definitively, are not yet forthcoming. Those results are anticipated in the not too distant future and will much better define that component of management in those most severely ill patients with AAV.
These recommendations serve as a framework for helping clinicians understand what is widely accepted as standard of care for these diseases but in no way can define individual treatment decisions as the authors acknowledge. Such decisions must become very personalized in relation to details of the patient’s individual comorbidities and other features of their medical and even socioeconomic status. For example, when choosing between rituximab and cyclophosphamide for remission induction in a young woman (or man, for that matter), future fertility concerns (which cyclophosphamide could potentially compromise) are very relevant. Moreover, the costs of rituximab are substantial, and the lack of superiority of rituximab over cyclophosphamide in many situations, particularly in patients with new severe disease, could be an important factor to consider when choosing which immunosuppressive will be used.
Many of the unanswered questions await results of ongoing or upcoming trials, including some addressing the relative efficacy of various remission maintenance regimens (rituximab vs. azathioprine) or the role of plasmapheresis. Many questions in AAV are not easily addressable in clinical trials, such as whether there are some groups of patients in whom remission maintenance therapy should never be withdrawn. However, such questions may be addressed through observational studies of the well-defined patient cohorts and registries that have been developed in the United States and Europe.
Robert F. Spiera, MD, is director of the Scleroderma, Vasculitis, & Myositis Center at the Hospital for Special Surgery, N.Y. He is also professor of clinical medicine at Cornell University, N.Y. He has received research funding and consulting fees from Roche/Genentech, which markets rituximab.
