Table 2:
Recent randomized placebo-controlled trials of corticosteroids in IgAN.
| STOP-IgAN (n = 162) | TESTING (n = 503) | NefIgArd (Part A) (n = 199) | |
|---|---|---|---|
| Population | Primary IgAN | Primary IgAN | Primary IgAN |
| Key exclusion criteria | Key exclusion criteria | Key exclusion criteria | |
| eGFR: <30 mL/min/1.73 m2 | eGFR: <20 mL/min/1.73 m2 | eGFR: <35 mL/min/1.73 m2 | |
| Proteinuria: <0.75 g/day after run-in | Proteinuria: <1 g/day | Proteinuria: <1 g/day | |
| BP: No upper limit | BP: >160/110 mmHg | BP: ≥140/90 mmHg | |
| Immunosuppression: any prior systemic IS | Immunosuppression: systemic IS treatment within 1 year | Immunosuppression: systemic IS treatment within 1 year | |
| Kidney biopsy: crescentic IgAN | Kidney biopsy: >50% crescents | Kidney biopsy: no limit on crescents | |
| Key baseline characteristics | Key baseline characteristics (total cohort) | Key baseline characteristics | |
| Race: 100% White | Race: 95% Asian, 5% White | Race: 12% Asian, 86% White, 2% Other | |
| Age: 44 years (mean) | Age: 36 years (median) | Age: 44 years (median) | |
| Gender M:F: 78:22 | Gender M:F: 60:40 | Gender M:F: 68:32 | |
| eGFR: 59 mL/min/1.73 m2 (mean) | eGFR: 58 mL/min/1.73 m2 (median) | eGFR: 55 mL/min/1.73 m2 (median) | |
| Proteinuria: 1.7 g/day (median) | Proteinuria: 2.0 g/day (median) | Proteinuria: 2.3 g/day (median) | |
| RAASi use: 98% (34% dual blockade) 6-month run-in | RAASi use: 99.9% 3-month run-in | RAASi use: 98% (5% dual blockade) for 3 months | |
| BP: 125/77 mmHg (mean) | BP: 124/80 mmHg (median) | BP: 126/78 mmHg (median) | |
| Intervention | eGFR >60: methylprednisolone 1 g daily IV × 3 doses at beginning of Months 1, 3 and 5; prednisolone 0.5 mg/kg alternate days PO for 6 month treatment | High-dose: methylprednisolone 0.6–0.8 mg/kg per day PO (max 48 mg/day) tapering by 8 mg/day/month for total treatment 6–8 months (n = 136) | 16 mg enteric-coated budesonide OD PO for 9 months |
| Or | Or | ||
| eGFR 30–59: cyclophosphamide 1.5 mg/kg/day for 3 months followed by azathioprine 1.5 mg/kg/day from Month 3 to Month 36, plus oral prednisolone 40 mg daily PO tapered to 7.5 mg over 6 months and continued for total 36 months | Low-dose: Methylprednisolone 0.4 mg/kg/day (max 32 mg/day) weaning by 4 mg/day/month, with prophylactic co-trimoxazolea (n = 121) | ||
| Comparator | Placebo | Placebo | Placebo |
| Outcome (intervention vs placebo) | Efficacy: primary outcome Full clinical remissionb at 3 years17% vs 5% (OR 4.8, P = .01)Decrease in eGFR by ≥15 mL/min/1.73 m2 at 3 years26% vs 28% (OR 0.89, P = .75) | Efficacy: primary outcome 40% reduction in eGFR, kidney failure, or death due to kidney disease Total cohort28.8% vs 43.1% (HR 0.53, P < .001)Low-dose cohort6% vs 17% (HR 0.27, no heterogeneity) | Efficacy: primary outcome Reduction in urinary PCR at 9 months31% reduction vs 5% reduction (P = .0003) |
| Key serious adverse events Overall: 35% vs 26%Deaths (n): 1 vs 1Infectionc: 10% vs 4%New DM: 11% vs 1% | Key serious adverse events—total cohort (low-dose) Overall: 10.9% vs 2.8% (6% vs 2.5%)Deaths (n): 6 vs 3 (1 vs 0)Infectionc: 7% vs 1% (4% vs 2%)New DM: 0.8% vs 0.0% (2% vs 0%) | Key serious adverse events Overall: 4% vs 1%Deaths (n): 0 vs 0Infectionc: 0% vs 0%New DM: 2% vs 0% |
aProphylactic co-trimoxazole was also given to those randomized to placebo after change to low-dose protocol.
bIn STOP-IgAN full clinical remission was defined as a urinary protein-creatinine ratio of <0.2 g/g and stable renal function with no more than 5 mL/min/1.73 m2 change in eGFR.
cSerious infectious adverse events were defined as infections requiring hospitalization in TESTING and NefIgArd; they were not specifically defined in STOP-IgAN.
OD = once per day; PO = administer orally; M = male; F = female; BP = blood pressure; IS = immunosuppression; IV = intravenously; PCR = protein-creatinine ratio; OR = odds ratio.