6/30/23, 2:16 AM TESTING Pathway Feedback Search Clinical Topics Home Studies TESTING TESTING Disease Immunoglobulin A nephropathy Trial question What is the effect of oral methylprednisolone in patients with IgA nephropathy and persistent proteinuria who are at risk of progression? Study design Multi-center Double blinded RCT Population Characteristics of study participants 37.0% female N = 262 63.0% male 262 patients (96 female, 166 male) Inclusion criteria: patients with IgA nephropathy and persistent proteinuria > 1 g/d and eGFR of 20-120 mL/min/1.73 m after at least 3 months of BP control and renin-angiotensin system blockade who are at risk of progression Key exclusion criteria: strong indication or contraindication for corticosteroid therapy, or the use of systemic immunosuppressive therapy in the previous year Interventions N=136 oral methylprednisolone (0.6-0.8 mg/kg/d; maximum 48 mg/d for 2 months, with subsequent weaning over 4-6 months) N=126 placebo (matching placebo for 2 months) https://web.pathway.md/studies/rec3vInWxjLkV1Aur 1/2 6/30/23, 2:16 AM TESTING Pathway Primary outcome End-stage kidney disease, death due to kidney failure, or a 40% decline in eGFR 15.9 % 15.9 11.9 % 8.0 % 5.9 Significant decrease 4.0 % NNT = 10 0.0 % Oral methylprednisolone Placebo Significant decrease in end-stage kidney disease, death due to kidney failure, or a 40% decline in eGFR (5.9% vs. 15.9%; HR 0.37, 95% CI 0.17 to 0.85) Secondary outcomes Significant increase in death, end-stage renal disease, or 40% decline in eGFR (7.4% vs. 15.9%; ARR 8.5, 95% CI 0.7 to 16.6) No significant difference in the incidence of eGFR decline (-1.79 mL/min/1.73 m /year vs. 6.95 mL/min/1.73 m /year; MD -5.15, 95% CI -9.89 to 0.42) Safety outcomes Significant differences in serious adverse events (14.7% vs. 3.2%, p = 0.001; risk difference 11.5%, 95% CI 4.8%-18.2%), mostly due to excess serious infections (8.1% vs. 0, p < 0.001; risk difference 8.1%, 95% CI 3.5%-13.9%). Conclusion In patients with IgA nephropathy and persistent proteinuria > 1 g/d and eGFR of 20-120 mL/min/1.73 m after at least 3 months of BP control and renin-angiotensin system blockade who are at risk of progression, oral methylprednisolone was superior to placebo with respect to a end- stage kidney disease, death due to kidney failure, or a 40% decline in eGFR. Reference Lv J, Zhang H, Wong MG et al. Effect of Oral Methylprednisolone on Clinical Outcomes in Patients With IgA Nephropathy: The TESTING Randomized Clinical Trial. JAMA. 2017 Aug 1;318(5):432- 442. Open reference URL https://web.pathway.md/studies/rec3vInWxjLkV1Aur 2/2