While the treatment of ANCA-associated vasculitis has taken strides away from highly toxic immunosuppressants to include an array of approaches based on biological drugs, there is plenty of room for treatment improvement.
Research at the Mayo Clinic is focusing on approaches to prevent relapses of inflammatory disease activity.
In a clinical update titled “Paradigm shift in the management of ANCA-associated vasculitis,” scientists shared the many treatment advances made in the field, and provided information on current trials testing a variety of new drugs and treatment strategies.
There are three forms of ANCA vasculitis that share certain features, but also have unique characteristics. These conditions are not always treated in the same way.
Since cyclophosphamide was approved about 40 years ago, it has been used to treat severe microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA), also known as Wegener’s granulomatosis.
The immunosuppressant is effective in harnessing disease activity in many patients, but also is linked to severe toxicity in the form of infertility and an increased risk of cancer.
Since then, other immunosuppressants, including methotrexate and CellCept (mycophenolate mofetil) has been successfully used in patients with milder forms of GPA or MPA.
The introduction of Rituxan (rituximab), however, fundamentally changed the treatment of severe ANCA vasculitis, researchers wrote. The drug targets a subset of immune B-cells.
Research has shown that disease activity in ANCA vasculitis is strongly linked to B-cells, whereas abnormally active T-cells also are found in patients in remission — suggesting they may guard more basic disease processes.
The RAVE clinical trial (NCT00104299) showed that Rituxan was similarly effective as cyclophosphamide is inducing remission in patients with severe GPA and MPA, but the drug’s safety profile is far better than that of cyclophosphamide.
The study also revealed that Rituxan was more effective than cyclophosphamide in patients with relapsing disease. The data made the U.S. Food and Drug Administration approve Rituxan, together with a glucocorticoid, for remission induction in severe GPA and MPA patients.
Mayo Clinic researchers followed up with a study showing that a single course of four once-weekly Rituxan infusions is equally effective in inducing remission as 18 months of continuous cyclophosphamide treatment followed by azathioprine.
Meanwhile, patients with eosinophilic granulomatosis with polyangiitis (EGPA), have continued treatment with glucocorticoids with the addition of cyclophosphamide when disease activity soars. But long-term treatment with glucocorticoids also poses severe health risks.
Researchers are exploring if mepolizumab — an antibody targeting the immune mediator IL-5 — may harness disease activity in patients with EGPA.
Clinical trials at the Mayo Clinic also explore other approaches. The clinic is part of a large Phase 3 study, called PEXIVAS (NCT00987389) that aims to clear if plasma exchange is an effective treatment for ANCA vasculitis.
The idea with the approach is to remove the ANCA antibodies from the blood, but earlier studies have produced variable results.
Many clinical trials also focus on maintaining remission. For instance, the Rituximab Vasculitis Maintenance Study Phase 3 trial (NCT01697267) is comparing Rituxan with azathioprine for remission maintenance in relapsing GPA and MPA patients.
Benlysta (belimumab) is another drug explored as a remission maintenance drug in the BREVAS Phase 3 study (NCT01663623), and the ABROGATE trial (NCT02108860) examines abatacept in patients with less severe GPA.
The many research efforts make it likely that even more effective and safe treatment approaches for various forms of ANCA vasculitis will emerge.