Trial to Explore If Low-dose Glucocorticoids May Improve Safety of ANCA Vasculitis Treatment
A clinical trial will assess whether low-dose glucocorticoids and Rituxan (rituximab) may be used as a safer way to treat ANCA-associated vasculitis (AAV).
Researchers at Chiba University Hospital in Japan believe the regimen may be effective and cause fewer side effects compared to current treatment approaches.
The trial particularly aims to explore whether it is possible to reduce deaths caused by infection or cardiovascular disease linked to current treatment, which employs high-dose glucocorticoids with immunosuppressants or Rituxan.
The research team describes the study, called LoVAS, in an article titled “Low-dose glucocorticoids plus rituximab versus high-dose glucocorticoids plus rituximab for remission induction in ANCA-associated vasculitis (LoVAS): protocol for a multicentre, open-label, randomised controlled trial.”
Published in the journal BMJ Open, the team argued that many of the side effects of current treatment — which, in addition to infections and heart disease include numerous non-fatal issues including osteoporosis and muscle disease — are mainly caused by the high doses of glucocorticoids.
Earlier trials found similar safety profiles of treatment with high-dose glucocorticoids plus cyclophosphamide (Cytoxan) or Rituxan, they said.
These treatments, however, trigger remission in up to 90 percent of ANCA vasculitis patients. They also lower mortality from 80 percent at one year to 25 percent at five years.
Therefore, researchers want to explore whether the high glucocorticoid doses are really necessary, or if lower doses may be as effective, but safer.
To do so, they launched a Phase 4, open-label trial (NCT02198248). The study will recruit 140 adult ANCA vasculitis patients from hospitals in Japan, who will be randomly assigned treatment with either low-dose (0.5 mg per kg body weight) or high-dose (1 mg per kg body weight) prednisolone per day, plus Rituxan.
Treatment will consist of a remission induction and a maintenance phase. While the high-dose group will continue to receive 10 mg of prednisolone in the maintenance phase, patients in the low-dose group will have their steroids tapered and removed after six months.
The primary outcome measure will, however, be remission rates at six months. The study will also explore how quickly patients reach remission and include an array of safety measurements. Relapse rates and safety issues will be assessed at several time points over two years.
“The results will contribute to establish a safer treatment strategy, which is still a big remaining issue in the treatment of AAV [ANCA-associated vasculitis],” researchers concluded.