Low daily doses of oral prednisone — 2.5 mg/day or less — during long-term remission maintenance therapy was associated with a higher rate of relapse in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in Japan, a study reports.
Most AAV patients are able to achieve remission when treated with high-dose glucocorticoids, such as prednisone, and concomitant immunosuppressants like methotrexate. Glucocorticoids are effective in reducing damaging inflammation caused by many immune system disorders.
However, treating AAV typically requires long-term use of glucocorticoids and immuno-suppressives to prevent relapse, and these medications are associated with adverse effects. These include risk of infection, osteoporosis, cardiovascular diseases and cancers, the study notes.
To learn more about the risk factors associated with relapse in patients on maintenance therapies in Japan, researchers studied (UMIN 000006373) 83 AAV patients who had achieved remission in a prior study, where they were treated for two years. Patients continued with either glucocorticoids alone, methotrexate alone, or a combination of a glucocorticoid and an immunosuppressant. Participants were followed for an additional 24 months.
During the study, 20 patients (24%) relapsed, a rate within the range of 15–46% reported in Europe and the United States.
Notably, prednisolone taken orally at a dose of 2.5 mg or less each day was a significant risk factor for relapse in these patients, researchers found. Those using this glucocorticoid at that dose were 3.1 times more likely to relapse, compared to those receiving a higher dose when entering the study.
“Longer relapse-free survival observed in patients treated with PSL [prednisolone] > 2.5 mg/day than in those treated with PSL ≤ 2.5 mg/day,” the researchers wrote.
At this study’s end, 95 percent of patients were alive. Causes of death included one thyroid cancer, one infection, and two unknown reasons. Among the group, four developed end-stage renal disease (ESRD) before entering the continuation trial and another during the study.
“One-quarter of patients with AAV relapsed during maintenance therapy, and relapse was associated with the dose of oral prednisolone 24 months after the initiation of remission induction therapy in Japan,” the team concluded.
The high relapse rates in European studies are usually associated with discontinuation of study drugs or oral glucocorticoids. This has led guidelines in Western countries to recommend that remission maintenance therapy for AAV should be continued for at least 24 months, and in some cases for up to five years, once disease remission is achieved.
“Further studies are needed to optimize maintenance therapy for Japanese patients with AAV,” the researchers added.