In patients with high-risk IgA nephropathy (IgAN), a 6 month to 9 month course of oral methylprednisolone may reduce the risk of major kidney events, according to new trial data presented at the American Society of Nephrology’s Kidney Week 2021.
In the double-blind Therapeutic Evaluation of STeroids in IgA Nephropathy Global (TESTING) trial, investigators randomly assigned 503 patients with IgAN and persistent proteinuria (more than 1 g/d despite optimized renin angiotensin blockade) to oral methylprednisolone (0.6 to 0.8mg/kg/d to a maximum 48mg/d for 2 months with tapering) or placebo. The primary endpoint was a composite of a persistent 40% decline in estimated glomerular filtration rate (eGFR), kidney failure, or death due to kidney disease.
Over a mean 4.2 years of follow-up, methylprednisolone treatment significantly reduced the risk of the primary composite outcome by 47%, Vlado Perkovic, MBBS, PhD, of The George Institute for Global Health, University of New South Wales in Sydney, Australia, reported in in a session on high-impact trials. The treatment significantly reduced the risk of kidney failure requiring dialysis or kidney transplantation by 41%,
In November 2015, due to an excess of serious infections in the steroid arm, the methylprednisolone dose was reduced to 0.4mg/kg/d to a maximum 32mg/d (with tapering) and Pneumocystis jirovecii pneumonia prophylaxis was added. The eGFR criterion was raised from at least 20 to at least 30mL/min/1.73 m2 (thereby excluding patients with stage 4 disease).
The full dose methylprednisolone regimen was significantly associated with a 42% reduction in risk for the primary endpoint over a mean 5.7 years of follow-up, Dr Perkovic reported. The reduced-dose steroid regimen was associated with a significant 73% reduction in the primary endpoint over a mean 2.5 years of follow-up.
The primary outcome results did not differ significantly by baseline proteinuria, kidney function, histology, age, or biopsy timing. Three-quarters of trial participants were from China. Among Chinese patients, methylprednisolone use was associated with a significant 39% reduction in risk for the primary outcome. Non-Chinese patients had a significant 76% reduction in risk with borderline significant heterogeneity observed between groups.
There was an excess of serious adverse events (SAEs) in the methylprednisolone vs placebo arm. Most infections occurred within the first 3 months of steroid treatment, Dr Perkovic pointed out. Fewer SAEs occurred in the low-dose than high-dose group, but even in the low dose group, 1 death occurred.
For each 100 patients treated, there would be 13.7 fewer primary outcomes, including 5.5 fewer kidney failure events, at a cost of 7.7 additional SAEs, according to Dr Perkovic. At the full steroid dose, there would be 11.8 fewer primary outcomes, including 5.8 fewer kidney failure events, at a cost of 11.7 additional SAEs. At the reduced dose, there would be 16.7 fewer primary outcomes, including 5.8 fewer kidney failure events, at a cost of 2.4 additional SAEs.
“The incidence of serious adverse events – particularly serious infections – is increased, but this was seen mainly with the full dose therapy, suggesting that a reduced-dose regimen may offer the best balance of risks and benefits,” Dr Perkovic concluded.
Disclosure: Pfizer provided the study drug. Please see the original reference for a full list of disclosures.
Perkovic V, Lv J, Geot Wong M, et al. The TESTING study: steroids vs. placebo in high risk IgA nephropathy. Presented at: Kidney Week 2021, November 2 to 7, 2021. Presentation FR-OR61.
This article originally appeared on Renal and Urology News