SWISS MEDICAL WEEKLY

Rituximab (RITUXAN)in the treatment of ANCA-associated vasculitides

16/02/2015 Leave a Comment

By Thomas Daikeler, et al. −  The antineutrophil cytoplasmic antibody-associated vasculitides are a group of primary vasculitides that affect predominantly small- to medium-sized blood vessels. This review explores the emerging role of rituximab in the management of this complex disorder.
Abstract
Antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) includes granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). Disease severity is dictated by the location and extent of the blood vessels affected.
If left untreated, systemic forms of AAV are often fatal. The advent of immunosuppressive therapy (cyclophosphamide plus glucocorticoids) has revolutionised the prognosis for patients with AAV, transforming the course of the disease from fatal to one that can be managed, though not without significant treatment-related toxicity. Today, standard therapy consists of high-dose glucocorticoids plus intravenous or oral cyclophosphamide over a period of 3–6 months for induction of remission. Plasma exchange has also been used to treat cases characterised by alveolar haemorrhage and acute renal insufficiency [20]. With these treatments, remission rates are between 30%–93% in GPA and 75%–89% in MPA. Once remission is achieved, this treatment is usually followed by maintenance therapy, since AAVs are chronic diseases with a high risk of relapse. Despite current maintenance treatments, around 50% of responders still relapse within 3–5 years and the 1–year mortality remains at around 12%–18%.
Recently, the monoclonal antibody rituximab was approved for the treatment of GPA and MPA, providing the first major alternative to cyclophosphamide for induction therapy of AAV. Rituximab is a monoclonal anti-CD20 antibody that selectively targets B cells and is an established treatment for rheumatoid arthritis and B cell lymphomas. Data for rituximab in the induction therapy of patients with newly-diagnosed AAV comes from two pivotal trials, RAVE (rituximab for ANCA-associated vasculitis) and RITUXVAS (rituximab versus cyclophosphamide in ANCA-associated vasculitis). Both trials were designed to compare the efficacy and safety of rituximab versus cyclophosphamide in the treatment of AAV. The findings from both trials demonstrate that rituximab has an efficacy in remission induction comparable to that of cyclophophamide and is likely superior in relapsing patients. EGPA patients were excluded from RAVE and RITUXVAS trials and results cannot be extrapolated to this category of patients.
RTX has also been tested as an alternative to azathioprine for maintenance treatment. The data support the use of RTX to maintain remission in patients at high risk of relapse or in patients who have experienced multiple relapses, or relapses while on alternative maintenance regimens. The optimal dosing schedule remains to be determined.
Although the safety profile of RTX in lymphoma and rheumatoid arthritis is well established, the situation in AAV is less clear-cut. Contraception is mandatory in fertile women after RTX treatment owing to the lack of robust information on the effect of RTX on newborns.
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This is a summary of a paper that was published on www.smw.ch. Must be cited as: Daikeler T, Kistler AD, Martin PY, Vogt B, Huynh-Do U. The role of rituximab in the treatment of ANCA-associated vasculitides (AAV). Swiss Med Wkly. 2015;145:w14103.