Rituxan for ANCA Associated Vasculitis
Dr. Jeffrey Landis, July 2019
Vasculitis is the inflammation of blood vessels. ANCA associated vasculitis is comprised mainly of 2 types of vasculitis: granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). These are 2 distinct entities.
GPA is an inflammation of the wall of the artery and areas around the artery which will create granulomas. These granulomas are destructive. Granulomas can be found in sinuses causing nose bleeds. Granulomas will cause destructive nodules in the lungs leading to cavitary lesions that will cause patients to bleed from the lungs. Granulomas will also cause destructive lesions in the kidneys leading to kidney failure. These are among the more common and deadly symptoms, but not the only ones. They can affect the joints, nerves, eyes, ears, skin, and heart valves. This is a very deadly disease that can move at great speed, as a person could transition from no symptoms to death within 2 weeks, if left untreated. However, the vasculitis generally does not progress this rapidly.
MPA is a destructive inflammation in the capillaries. This vasculitis seems to affect the kidneys and lungs alone. It has been known to affect some nerves, eyes, joints, and skin as well. MPA affects the kidneys 100% of the time and 24-45% will require dialysis. Over 50% of MPA patients have lung involvement. 12-29% will have severe bleeding from the lungs. 32% have permanent scarring of the lungs with permanent loss of lung function. This is also a very deadly vasculitis. There is a 31% mortality if there is bleeding from the lungs.
The standard therapy is very high doses of intravenous steroids that shuts down the majority of the immune system quickly. This was followed by a high dose steroid taper and oral cyclophosphamide.
In the past, the cyclophosphamide was given for 6 months followed by a year and a half of azathioprine. The problem with this treatment was the cyclophosphamide. Cyclophosphamide is a chemotherapeutic agent that comes with its own set of severe side effects. It would cause hair loss, infertility, increased risk for bladder cancer, and bone marrow damage among other things.
Rituxan came out in 1997 for the treatment of certain lymphomas. It targets CD20 and causes the destruction of these B-cells. This causes a B-cell depletion in the immune system as well as the lymphoma. It was found to work well for rheumatoid arthritis and later it was tested in vasculitis with success. It has come to replace cyclophosphamide as the treatment for vasculitis. The side effects to the Rituxan can be an increased risk for infections, infusion reactions, JC virus reactivation (which is very rare), bowel perforation and immunosuppression.
The initial infusion is weekly for 4 weeks. At 6 months, the patient gets 2 infusions 2 weeks apart. The patient then receives 1 infusion every 6 months. The infusion time is initially about 4 hours long with subsequent infusions being 3 hours long. The most common reaction is an allergic reaction in the first 2 hours of the infusion.