Rituximab in children with steroid-dependent nephrotic syndrome: A multicenter, open-label, noninferiority, randomized controlled trial

Pietro Ravani, Roberta Rossi, Alice Bonanni, Robert R. Quinn, Felice Sica, Monica Bodria, Andrea Pasini, Giovanni Montini, Alberto Edefonti, Mirco Belingheri, Donatella De Giovanni, Giancarlo Barbano, Ludovica Degl'Innocenti, Francesco Scolari, Luisa Murer, Jochen Reiser, Alessia Fornoni, Gian Marco Ghiggeri

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Abstract

Steroid-dependent nephrotic syndrome (SDNS) carries a high risk of toxicity fromsteroids or steroid-sparing agents. This open-label,noninferiority,randomized controlled trial at four sites in Italy tested whether rituximab is noninferior to steroids in maintaining remission in juvenile SDNS. We enrolled children age 1-16 years who had developed SDNS in the previous 6-12 months and weremaintained in remission with high prednisone doses (≥0.7mg/kg per day). We randomly assigned participants to continue prednisone alone for 1 month (control) or to add a single intravenous infusion of rituximab (375 mg/m2; intervention). Prednisone was tapered in both groups after 1month. For noninferiority, rituximab had to permit steroid withdrawal and maintain 3-month proteinuria (mg/m2 per day) within a prespecified noninferiority margin of three times the levels among controls (primary outcome).We followed participants for ≥1 year to compare risk of relapse (secondary outcome). Fifteen children per group (21 boys; mean age, 7 years [range, 2.6-13.5 years]) were enrolled and followed for ≤60 months (median, 22months). Three-month proteinuria was 42%lower in the rituximab group (geometricmean ratio, 0.58; 95%confidence interval, 0.18 to 1.95 [i.e., within the noninferiority margin of three times the levels in controls]). All but one child in the control group relapsed within 6months; median timeto relapse in the rituximab group was 18months (95% confidence interval, 9 to 32 months). In the rituximab group, nausea and skin rash during infusion were common; transient acute arthritis occurred in one child. In conclusion, rituximab was noninferior to steroids for the treatment of juvenile SDNS.

Original languageEnglish (US)
Pages (from-to)2259-2266
Number of pages8
JournalJournal of the American Society of Nephrology
Volume26
Issue number9
DOIs
StatePublished - Sep 1 2015

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Nephrotic Syndrome
Randomized Controlled Trials
Steroids
Prednisone
Proteinuria
Confidence Intervals
Recurrence
Rituximab
Exanthema
Intravenous Infusions
Nausea
Italy
Arthritis
Control Groups

ASJC Scopus subject areas

  • Nephrology

Cite this

Rituximab in children with steroid-dependent nephrotic syndrome : A multicenter, open-label, noninferiority, randomized controlled trial. / Ravani, Pietro; Rossi, Roberta; Bonanni, Alice; Quinn, Robert R.; Sica, Felice; Bodria, Monica; Pasini, Andrea; Montini, Giovanni; Edefonti, Alberto; Belingheri, Mirco; De Giovanni, Donatella; Barbano, Giancarlo; Degl'Innocenti, Ludovica; Scolari, Francesco; Murer, Luisa; Reiser, Jochen; Fornoni, Alessia; Ghiggeri, Gian Marco.

In: Journal of the American Society of Nephrology, Vol. 26, No. 9, 01.09.2015, p. 2259-2266.

Research output: Contribution to journalArticle

Ravani, P, Rossi, R, Bonanni, A, Quinn, RR, Sica, F, Bodria, M, Pasini, A, Montini, G, Edefonti, A, Belingheri, M, De Giovanni, D, Barbano, G, Degl'Innocenti, L, Scolari, F, Murer, L, Reiser, J, Fornoni, A & Ghiggeri, GM 2015, 'Rituximab in children with steroid-dependent nephrotic syndrome: A multicenter, open-label, noninferiority, randomized controlled trial', Journal of the American Society of Nephrology, vol. 26, no. 9, pp. 2259-2266. https://doi.org/10.1681/ASN.2014080799
Ravani, Pietro ; Rossi, Roberta ; Bonanni, Alice ; Quinn, Robert R. ; Sica, Felice ; Bodria, Monica ; Pasini, Andrea ; Montini, Giovanni ; Edefonti, Alberto ; Belingheri, Mirco ; De Giovanni, Donatella ; Barbano, Giancarlo ; Degl'Innocenti, Ludovica ; Scolari, Francesco ; Murer, Luisa ; Reiser, Jochen ; Fornoni, Alessia ; Ghiggeri, Gian Marco. / Rituximab in children with steroid-dependent nephrotic syndrome : A multicenter, open-label, noninferiority, randomized controlled trial. In: Journal of the American Society of Nephrology. 2015 ; Vol. 26, No. 9. pp. 2259-2266.
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abstract = "Steroid-dependent nephrotic syndrome (SDNS) carries a high risk of toxicity fromsteroids or steroid-sparing agents. This open-label,noninferiority,randomized controlled trial at four sites in Italy tested whether rituximab is noninferior to steroids in maintaining remission in juvenile SDNS. We enrolled children age 1-16 years who had developed SDNS in the previous 6-12 months and weremaintained in remission with high prednisone doses (≥0.7mg/kg per day). We randomly assigned participants to continue prednisone alone for 1 month (control) or to add a single intravenous infusion of rituximab (375 mg/m2; intervention). Prednisone was tapered in both groups after 1month. For noninferiority, rituximab had to permit steroid withdrawal and maintain 3-month proteinuria (mg/m2 per day) within a prespecified noninferiority margin of three times the levels among controls (primary outcome).We followed participants for ≥1 year to compare risk of relapse (secondary outcome). Fifteen children per group (21 boys; mean age, 7 years [range, 2.6-13.5 years]) were enrolled and followed for ≤60 months (median, 22months). Three-month proteinuria was 42{\%}lower in the rituximab group (geometricmean ratio, 0.58; 95{\%}confidence interval, 0.18 to 1.95 [i.e., within the noninferiority margin of three times the levels in controls]). All but one child in the control group relapsed within 6months; median timeto relapse in the rituximab group was 18months (95{\%} confidence interval, 9 to 32 months). In the rituximab group, nausea and skin rash during infusion were common; transient acute arthritis occurred in one child. In conclusion, rituximab was noninferior to steroids for the treatment of juvenile SDNS.",
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AU - Ravani, Pietro

AU - Rossi, Roberta

AU - Bonanni, Alice

AU - Quinn, Robert R.

AU - Sica, Felice

AU - Bodria, Monica

AU - Pasini, Andrea

AU - Montini, Giovanni

AU - Edefonti, Alberto

AU - Belingheri, Mirco

AU - De Giovanni, Donatella

AU - Barbano, Giancarlo

AU - Degl'Innocenti, Ludovica

AU - Scolari, Francesco

AU - Murer, Luisa

AU - Reiser, Jochen

AU - Fornoni, Alessia

AU - Ghiggeri, Gian Marco

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N2 - Steroid-dependent nephrotic syndrome (SDNS) carries a high risk of toxicity fromsteroids or steroid-sparing agents. This open-label,noninferiority,randomized controlled trial at four sites in Italy tested whether rituximab is noninferior to steroids in maintaining remission in juvenile SDNS. We enrolled children age 1-16 years who had developed SDNS in the previous 6-12 months and weremaintained in remission with high prednisone doses (≥0.7mg/kg per day). We randomly assigned participants to continue prednisone alone for 1 month (control) or to add a single intravenous infusion of rituximab (375 mg/m2; intervention). Prednisone was tapered in both groups after 1month. For noninferiority, rituximab had to permit steroid withdrawal and maintain 3-month proteinuria (mg/m2 per day) within a prespecified noninferiority margin of three times the levels among controls (primary outcome).We followed participants for ≥1 year to compare risk of relapse (secondary outcome). Fifteen children per group (21 boys; mean age, 7 years [range, 2.6-13.5 years]) were enrolled and followed for ≤60 months (median, 22months). Three-month proteinuria was 42%lower in the rituximab group (geometricmean ratio, 0.58; 95%confidence interval, 0.18 to 1.95 [i.e., within the noninferiority margin of three times the levels in controls]). All but one child in the control group relapsed within 6months; median timeto relapse in the rituximab group was 18months (95% confidence interval, 9 to 32 months). In the rituximab group, nausea and skin rash during infusion were common; transient acute arthritis occurred in one child. In conclusion, rituximab was noninferior to steroids for the treatment of juvenile SDNS.

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