Dr DANA KIM1,2, JICHENG LV3, MICHELLE HLADUNEWICH4, VIVEKANAND JHA5,6,7, LAI SEONG HOOI8, HELEN MONAGHAN1, LAURENT BILLOT1, HONG ZHANG3, VLADO PERKOVIC1, MUH GEOT WONG1,2,9
1The George Institute for Global Health, University of New South Wales, Sydney, Australia, 2The University of Sydney, Sydney, Australia, 3Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China, 4Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada, 5The George Institute for Global Health India, UNSW, New Delhi, India, 6Prasanna School of Public Health, Manipal Academy of Higher Education, Manipal, India, 7The George Institute for Global Health, School of Public Health, Imperial College London, London, United Kingdom, 8Sultanah Aminah Hospital, Johor Bahru, Malaysia, 9Department of Renal Medicine, Concord Repatriation General Hospital, Sydney, Australia
Aim: To assess the efficacy and safety of reduced-dose oral methylprednisone in IgA nephropathy (IgAN).
Background: The TESTING study recently reported that corticosteroids reduce the risk of major kidney events in IgAN with high risk of progression, but also increase the risk of serious adverse events (SAE) primarily with full-dose therapy. The risk-benefit balance of the reduced-dose regimen is important to define.
Methods: TESTING randomized people with IgAN to methylprednisone or placebo. Safety concerns led to a protocol adjustment to a reduced methylprednisone dose. Between 2017-2019, patients with IgAN, proteinuria>1g/d despite renin-angiotensin-system blockade and eGFR 30-120ml/min/1.73m2 were randomized to reduced-dose methylprednisone (0.4mg/kg/d, max 32mg/d, tapered over 6-9m) or placebo. The primary outcome was major kidney events: a composite of 40% decline in eGFR, kidney failure or death due to kidney disease.
Results: 241 participants (42% female, mean age 37years, eGFR 65ml/min/1.73m2, proteinuria 2.48g/d, 53% Chinese, 7% Caucasian) were randomized to methylprednisone (121) or placebo (120). Methylprednisone therapy reduced major kidney events (HR 0.24, 95%CI 0.10-0.58, p=0.002) and slowed the rate of eGFR decline (-0.74ml/min/1.73m2/yr vs -3.03ml/min/1.73m2/yr) and proteinuria levels (1.58g/d vs 2.41g/d). SAEs occurred in 5% vs 2.5% in the methylprednisone and placebo arms respectively (HR 1.97, 95%CI 0.49-7.90, p=0.34) while infection requiring hospitalisation occurred in 4.1% vs 1.7%, p=0.44. The number-needed-to-treat (NNT) to prevent one primary outcome and one kidney failure event at 2.5years was 6 (95%CI 4.6-8.9) and 16.7 (95%CI 10.7-38) respectively, while the NNT for harm for one SAE was 41 (95%CI 17.4- -116.1).
Conclusion: Reduced-dose methylprednisone is effective in preventing major kidney events in IgAN, with benefits that appear to outweigh the modestly increased risk of steroid-related SAEs.
Biography:
Dana Kim is a nephrologist and a research associate at the George Institute for Global Health. She is currently undertaking a PhD at the University of Sydney under the supervision of A/Prof Muh Geot Wong.