The new study does not support this approach. Dr. Hojjati was not affiliated with the new study by Furuta et al., but she is familiar with the urge to prescribe higher dosages of steroids. This impulse can occur even when physicians know higher dosages don’t necessarily lead to better outcomes. This lingering inclination is one of the reasons researchers continue to document the noninferiority of lower doses of steroids.
Study Details
Furuta et al. conducted this randomized, clinical trial in multiple centers in Japan between November 2014 and June 2019. The investigators designed the study to be open label in acknowledgement of the difficulty in blinding physicians to the effects of high-dose glucocorticoids on patients’ appearances and blood tests.
The study enrolled only newly diagnosed patients without comorbidities who required glucocorticoids. The researchers randomized the 140 patients (57.8% women) to receive reduced-dose prednisolone (0.5 mg/kg per day) plus rituximab (375 mg/m2 per week, four doses) or high-dose prednisolone (1 mg/kg per day) plus rituximab (375 mg/m2 per week).
The study did have some prescribing flexibility. It allowed physicians to postpone the initiation of the prednisolone discontinuation step in the reduced-dose group if the predefined conditions were met and an investigator suspected persistent low disease activity. These predefined conditions include a Birmingham Vasculitis Activity Score (version 3) that did not reach 0 or C-reactive protein (CRP) and ANCA values that were not normalized. Even with this flexibility, at the end of the study, the median cumulative dose of prednisolone over the six-month period was 1,318 mg in the low-dose group and 4,151.25 mg in the high-dose group.
At six months, approximately 70% of patients in each group achieved remission. When the researchers performed adjusted analyses that accounted for ANCA subtype, age and kidney function, they also found no differences between the treatment groups. A post hoc analysis also revealed no differences in the Vasculitis Damage Index scores between the two groups at six months.
The researchers used the Medical Outcomes Study 36-Item Short Form to measure quality of life at six months and saw no differences between the groups in either the physical or mental component summary scores. At six months, the Birmingham Vasculitis Activity Scores also did not significantly differ between the two groups, and the investigators saw no differences in median serum CRP levels or estimated glomerular filtration rate (eGFR) levels between the two groups.
