Table 2.
Summary of clinical trials on the use of rituximab in childhood idiopathic nephrotic syndrome
| Study | Study Design | Study Population | Age (yr) | No. of Patients Analyzed | Follow-Up Period (mo) | Rituximab Arm | Control/Comparative Arm | Primary End Points | Results |
|---|---|---|---|---|---|---|---|---|---|
| Ravani et al.,29 2011 | Open-label, RCT | CNI-dependent SDNS | 1–16 | 54 | 3 | Add-on RTX 375 mg/m2 × 1–2 (n=27) | Steroid and CNI (n=27) | Proteinuria at 3 months | 3-month proteinuria was 70% lower in the RTX arm (95% CI, 35 to 86); relapse rates were 18.5% (RTX) and 48.1% (control) (P = 0.029) |
| Magnasco et al.,30 2012 | Open-label, RCT | SRNS unresponsive to CNI | 1–16 | 31 | 3 | Add-on RTX 375 mg/m2 × 2 (n=16) | Steroid and CNI (n=15) | Proteinuria reduction at 3 months | 3-month proteinuria was not reduced in the RTX arm (change, −12% [95% CI, −73 to 110]; P = 0.77) |
| Iijima et al.,5 2014 | Double-blind RCT | Complicated FRNS/SDNS | ≥2 | 48 | 12 | 375 mg/m2 × 4 (n=24) | Placebo (n=24) | Relapse-free remission | Remission period, RTX versus placebo: 267 days (95% CI, 223 to 374) versus 101 days (95% CI, 70 to 155); HR, 0.27, 95% CI, 0.14 to 0.53; P<0.0001 |
| Ruggenenti et al.,7 2014 | Off-on trial | FRNS or SDNS, with underlying MCD or FSGS | Not specified | 10 children and 20 adults | 12 | 375 mg/m2 × 1 (n=28) or × 2 (n=2) | Status 1 year prior to RTX | Number of relapses and steroid maintenance dose | Relapse per year decreased from 2.5 (IQR, 2–4) to 0.5 (IQR, 0–1); P<0.001; steroid dose decreased from 0.27 mg/kg (IQR, 0.19–0.60) to 0 mg/kg (IQR, 0–0.23); P<0.001 |
| Ravani et al.,6 2015 | Open-label, noninferiority, RCT | SDNS | 1–16 | 30 | 12 | Add-on RTX 375 mg/m2 × 1 (n=15) | Prednisolone or steroid-sparing agents (n=15) | Proteinuria at 3 months and risk of relapse | 3-month proteinuria was 42% lower in the RTX arm. The risk of relapse was reduced by 98% in RTX arm (HR, 0.02; 95% CI, 0.01 to 0.15) |
| Ahn et al.,31 2018 | Open-label, RCT | CNI-dependent SDNS | <24 | 51 | 12 | Add-on RTX 375 mg/m2 × 1–2 (n=35) | Steroid and CNI tapering (n=16) | Relapse-free remission at 6 months | Remission rates, RTX versus control: 74.3% versus 31.3%; P = 0.003 |
| Basu et al.,32 2018 | Open-label, RCT | SDNS not previously treated with steroid-sparing agent | 3–16 | 120 | 12 | 375 mg/m2 × 2 (n=60) | Tacrolimus with tapering of alternate day steroid (n=60) | Relapse-free remission at 12 months | Remission, RTX versus tacrolimus: 54 (90.0%) versus 38 (63.3%); P<0.001; OR, 5.21; 95% CI, 1.93 to 14.07 |
| Ravani et al.,33 2021 | Open-label, RCT | SDNS | 3–24 | 30 | 12 | 375 mg/m2 × 1 (n=15) | MMF (750 mg/m2 per day) (n=15) | Relapse at 12 months | Relapse, RTX versus MMF: 2 (13%) versus 12 (80%); P = 0.008. A significantly higher odds of relapse among children in the MMF arm (OR, 26; 95% CI, 2.9 to 311.0). The study was terminated early due to unexpectedly high rates of relapse in the MMF arm |
| Ravani et al.,16 2021 | Open-label, RCT | CNI-dependent SDNS | 2–24 | 140 | 24 | 375 mg/m2 × 1 (n=70) | Ofatumumab 1.50 g/1.73 m2 × 1 (n=70) | Relapse at 12 months | Relapse, RTX versus ofatumumab 36 (51%) versus 37 (53%); OR, 1.06; 95% CI, 0.55 to 2.06 |
| Mathew et al.,34 2022 | Open-label, noninferiority, RCT | Complicated FRNS/SDNS | 3–18 | 40 | 12 | 375 mg/m2 × 2 (n=20) | Tacrolimus (n=20) | Relapse-free remission at 12 months | Remission, RTX versus tacrolimus: 11 (55%) versus 11 (55%). Noninferiority of RTX to tacrolimus was not demonstrated |
RCT, randomized controlled trial; CNI, calcineurin inhibitor; SDNS, steroid-dependent nephrotic syndrome; RTX, rituximab; CI, confidence interval; SRNS, steroid-resistant nephrotic syndrome; FRNS, frequently relapsing nephrotic syndrome; HR, hazard ratio; MCD, minimal change disease; FSGS, focal segmental glomerulosclerosis; IQR, interquartile range; MMF, mycophenolate mofetil; OR, odds ratio.