Rituximab in steroid-dependent or frequently relapsing idiopathic nephrotic syndrome.
The outcome of steroid-dependent or frequently relapsing nephrotic syndrome of minimal change disease (MCD), mesangial proliferative GN (MesGN), or FSGS may be poor and with major treatment toxicity. This academic, multicenter, off-on trial (ClinicalTrials.gov #NCT00981838) primarily evaluated the effects of rituximab therapy followed by immunosuppression withdrawal on disease recurrence in 10 children and 20 adults with MCD/MesGN (n=22) or FSGS who had suffered ≥2 recurrences over the previous year and were in steroid-induced remission for ≥1 month. Participants received one dose (n=28) or two doses of rituximab (375 mg/m(2) intravenously). At 1 year, all patients were in remission: 18 were treatment-free and 15 never relapsed. Compared with the year before rituximab treatment, total relapses decreased from 88 to 22 and the per-patient median number of relapses decreased from 2.5 (interquartile range [IQR], 2-4) to 0.5 (IQR, 0-1; P<0.001) during 1 year of follow-up. Reduction was significant across subgroups (children, adults, MCD/MesGN, and FSGS; P<0.01). After rituximab, the per-patient steroid maintenance median dose decreased from 0.27 mg/kg (IQR, 0.19-0.60) to 0 mg/kg (IQR, 0-0.23) (P<0.001), and the median cumulative dose to achieve relapse remission decreased from 19.5 mg/kg (IQR, 13.0-29.2) to 0.5 mg/kg (IQR, 0-9.4) (P<0.001). Furthermore, the mean estimated GFR increased from 111.3±25.7 to 121.8±29.2 ml/min per 1.73 m(2) (P=0.01), with the largest increases in children and in FSGS subgroups. The mean height z score slope stabilized in children (P<0.01). Treatment was well tolerated. Rituximab effectively and safely prevented recurrences and reduced the need for immunosuppression in steroid-dependent or frequently relapsing nephrotic syndrome, and halted disease-associated growth deficit in children.
IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri," Clinical Research Center for Rare Diseases "Aldo e Cele Daccò," Ranica, Bergamo, Italy;
Piero
P
Ruggenenti
Barbara
B
Ruggiero
Paolo
P
Cravedi
Marina
M
Vivarelli
Laura
L
Massella
Maddalena
M
Marasà
Antonietta
A
Chianca
Nadia
N
Rubis
Bogdan
B
Ene-Iordache
Michael
M
Rudnicki
Rosa Maria
RM
Pollastro
Giovambattista
G
Capasso
Antonio
A
Pisani
Marco
M
Pennesi
Francesco
F
Emma
Giuseppe
G
Remuzzi
D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D002648:Child; D005260:Female; D015432:Glomerulonephritis, Membranoproliferative / Q000150:complications; D005923:Glomerulosclerosis, Focal Segmental / Q000150:complications; D006801:Humans; D008297:Male; D008875:Middle Aged; D009402:Nephrosis, Lipoid / Q000150:complications; D009404:Nephrotic Syndrome / Q000188:drug therapy*; D012008:Recurrence; D000069283:Rituximab
D000305:Adrenal Cortex Hormones; D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab