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Abstract: FR-OR61

The TESTING Study: Steroids vs. Placebo in High Risk IgA Nephropathy

Session Information

Category: Glomerular Diseases

  • 1203 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Perkovic, Vlado, The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, Australia
  • Lv, Jicheng, Peking University First Hospital, Beijing, China
  • Wong, Muh Geot, The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, Australia
  • Hladunewich, Michelle A., Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
  • Jha, Vivekanand, The George Institute for Global Health India, New Delhi, India
  • Monaghan, Helen, The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, Australia
  • Zhang, Hong, Peking University First Hospital, Beijing, China

Group or Team Name

  • The TESTING Study Group
Background

The Therapeutic Evaluation of STeroids in IgA Nephropathy Global (TESTING) study assessed the effects of oral methylprednisolone compared to placebo on major kidney outcomes and safety in IgAN.

Methods

This investigator-initiated, double-blind randomized trial included people with IgAN, proteinuria ≥1g/day and eGFR 20-120 mL/min/1.73m2, following ≥3 months of optimized background care including RAS blockade. Participants were randomized 1:1 to methylprednisolone (0.6-0.8 mg/kg/day, maximum 48 mg/day, for 2 months then weaning by 8mg/day/month) or to matching placebo. In 2016, due to an excess of serious infections in the steroid arm, the methylprednisolone dose was reduced (0.4 mg/kg/day, maximum 32 mg/day, weaning by 4 mg/day/month) and pneumocystis jirovecii prophylaxis added. The primary endpoint was the composite of 40% eGFR decline or kidney failure (dialysis, transplantation or death due to kidney disease) with prespecified secondary and safety outcomes.

Results

In total, 503 participants (mean age 38 years, 39% female, mean eGFR 61.5 mL/min/1.73m2, proteinuria 2.46 g/day) were randomised to methylprednisolone (257) or placebo (246), including 262 to the full dose and 241 to the reduced dose protocols.
Over 4.2 years average follow up, methylprednisolone reduced the risk of the primary outcome by 47% (event rate 7.0 vs 11.8/100 patient years, HR 0.53, 95% CI 0.39-0.72, p <0.0001), and ESKD by 41% (HR 0.59, CI 0.40-0.87, p=0.008). The reduction in risk was seen across both dose protocols (p heterogeneity 0.11): full dose HR 0.58 (95% CI 0.41-0.81), reduced dose HR 0.27 (95% CI 0.11-0.65).
Serious adverse events were more frequent with steroids compared to placebo (28 vs 7 patients, p=0.0004), particularly with the full dose (22 vs 4, p=0.0003) vs the reduced dose regimen (6 vs 3, p=0.50).

Conclusion

Steroids reduce the risk of major kidney outcomes and kidney failure in people with high risk IgAN. The incidence of serious adverse events is increased mainly with high dose therapy.

*joint first (JL MW)/senior authors (HZ VP)

Funding

  • Government Support - Non-U.S.