Treatment with methylprednisolone reduces the risk for disease progression in patients with IgA nephropathy (IgAN) and proteinuria of 1 g per day or greater who are receiving optimal supportive therapy, but it carries an excess risk for infection, investigators reported in JAMA.
In the Therapeutic Effects of Steroids in IgA Nephropathy Global (TESTING) randomized trial, a 6- to 9-month course of the oral glucocorticoid methylprednisolone significantly reduced the risk for the primary outcome by a significant 47% compared with placebo, according to Hong Zhang, MD, PhD, of Peking University First Hospital, Beijing, China, and colleagues. The primary outcome was a composite of a 40% decrease in estimated glomerular filtration rate (eGFR), kidney failure, or death due to kidney disease.
The study enrolled 503 patients, three-quarters of whom were Chinese. The primary outcome occurred in 74 of 257 patients (28.8%) receiving oral methylprednisolone and 106 of 246 patients (43.1%) receiving placebo over a mean 4.2 years of follow-up. Treatment led to a 4.8% absolute annual decline in the composite outcome, Dr Zhang’s team reported. At baseline, patients’ eGFR was 20 to 120 mL/min/1.73 m2. The annual rate of eGFR decline was 2.50 vs 4.97 mL/min/1.73 m2 per year in the methylprednisolone vs placebo group, respectively.
The first 136 patients randomly assigned to oral methylprednisolone received 0.6-0.8 mg/kg/d to a maximum of 48 mg/d, with tapering by 8 mg/d/mo. The investigators identified an excess of serious infections and subsequently reduced the dose to 0.4 mg/kg/d to a maximum of 32 mg/d, with tapering by 4 mg/d/mo. They also administered sulfamethoxazole-trimethoprim to all remaining patients as prophylaxis against pneumocystis pneumonia. Full-dose and reduced-dose methylprednisolone were significantly associated with a 42% and 73% lower risk for the composite outcome, respectively.
Dr Zhang and colleagues reported that time-averaged mean 24-hour urine protein excretion was significantly lower in the methylprednisolone than placebo group (1.70 vs 2.39 g/d) but the benefit decreased over time and was no longer observed at 36 months.
Serious adverse events, such as excess hospitalizations and infections, occurred more frequently with methylprednisolone vs placebo (10.9% vs 2.8%), mostly with the full-dose regimen, the investigators reported. Four infection-related events led to death in the methylprednisolone group.
In an accompanying editorial, Kirk N. Campbell, MD, of Icahn School of Medicine at Mount Sinai, New York, New York, noted that guidelines from Kidney Disease: Improving Global Outcomes (KDIGO) recommend clinical trials for high-risk patients with IgAN but allow cautious use of glucocorticoids after a discussion of risks and benefits.
“As a result of the TESTING data, patient-physician discussions can now be better informed, particularly around the question of safety,” according to Dr Campbell.
Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Lv J, Wong MG, Hladunewich MA, et al. Effect of oral methylprednisolone on decline in kidney function or kidney failure in patients with IgA nephropathy. JAMA. Published online May 17, 2022. 327(19):1888-1898. doi:10.1001/jama.2022.5368
Campbell KN. Oral glucocorticoids for IgA nephropathy. JAMA. Published online May 17, 2022. 327(19):1872-1874. doi:10.1001/jama.2022.4638