Methylprednisolone improves major kidney outcomes in patients with IgAN

Treatment with methylprednisolone reduces the risk of kidney composite outcomes, including kidney failure, 40 percent decline in eGFR, or death due to kidney disease, in patients with IgA nephropathy (IgAN), according to the TESTING* study presented at ASN Kidney Week 2021.

This investigator-initiated, double-blind, multicentre trial included 503 patients (mean age 37.9 years, 39.4 percent female) with IgAN (mean eGFR 61.5 mL/min/1.73 m², proteinuria 2.42 g/day) who were at high risk for disease progression and were receiving optimized background therapy (ACE inhibitors or ARBs) for ≥3 months prior to randomization. Participants were randomly assigned to receive either oral methylprednisolone (n=257; 0.6–0.8 mg/kg/day for 2 months, with a maximum dose of 48 mg/day, and then tapered by 8 mg/day/month) or placebo (n=246). [ASN Kidney Week 2021, abstract FR-OR61]

In 2016, due to excess serious adverse events (AEs), the Data Monitoring Committee suggests that the trial should not be continued in its current form, and therefore the methylprednisolone dose was reduced to 0.4 mg/kg/day (maximum 32 mg/day, and then weaning by 4 mg/day/month).

At a mean follow-up of 4.2 years, patients treated with methylprednisolone achieved a significant reduction in the risk of kidney composite outcomes compared with placebo (hazard ratio [HR], 0.53; p<0.0001).

With regard to individual components of the kidney composite endpoints, the methylprednisolone arm also achieved a reduced risk of kidney failure (HR, 0.59; p=0.008), 40 percent decline in eGFR (HR, 0.44; p<0.0001), and death due to kidney failure (HR, 0.93; p=0.96) compared with placebo.

In a subgroup analysis of methylprednisolone dosing protocols, both full and reduced doses of methylprednisolone demonstrated a reduced risk of kidney composite outcomes after a mean follow-up of 5.7 years (HR, 0.58) and 2.5 years (HR, 0.27; p heterogeneity=0.11), respectively, vs placebo.

“[Overall, the] kidney protective effect [of methylprednisolone] was consistent across [all] prespecified subgroups,” said lead author Professor Vlado Perkovic from the George Institute for Global Health, University of New South Wales in Sydney, New South Wales, Australia.

However, the number of serious AEs occurred more frequently in the methylprednisolone arm vs the placebo arm overall (37 vs 8 events), particularly with the full dose regimen (30 vs 5 events), but there was no clear difference between treatment groups with the reduced dose regimen.

“In people with IgAN at high risk, a 6–9 month course of oral methylprednisolone reduced the risk of major kidney outcomes by 47 percent, and kidney failure by 41 percent, Vlado concluded.

“[Of note,] the incidence of serious AEs, particularly serious infections, is increased, but this was seen mainly with full dose therapy suggesting that the reduced dose regimen may offer the best balanced of risk and benefit in the future,” he highlighted.