Magnasco 2012.

Methods	Study design: parallel RCT Time frame: 2007 to 2010 Follow‐up period: whole study 18 months
Participants	Setting: paediatric nephrology centres (4) Country: Italy Children aged 16 years or younger; eGFR > 60 mL/min/1.73 m2; history of INS unresponsive to the combination of prednisone and CNI for at least 6 months FSGS (19); MCD (7); biopsy not performed (4); inadequate material (1) Initial steroid resistance (16); late steroid resistance (15) Number: RTX group (15); control group (16) Mean age ± SD (years): RTX group (8.5 ± 4.4); control group (7.3 ± 3.7) Sex (M/F): RTX group (10/6); control group (9/6) Exclusion criteria: infantile onset (< 1 year); previous episodes of macrohaematuria; hepatitis B virus, hepatitis C virus or HIV infection; positivity for any marker of autoimmunity; low C3 levels; positive results on genetic testing for NPHS2 and WT1
Interventions	RTX group 2 doses IV RTX 375 mg/m2; first dose at randomisation and second dose 2 weeks later Control group No additional intervention other than standard therapy Co‐interventions Prednisolone, tapered off by 0.3 mg/kg/week if proteinuria < 1 g/d/m2 CNI (at pre‐enrolment doses): TAC (16), cyclosporin (15) for RTX group, after 2 weeks from prednisone withdrawal, CNI was decreased by 50% and ceased after 2 additional weeks ARB or ACEi in 25 participants
Outcomes	Proteinuria at baseline and 3 months (performed at a central lab) Numbers with complete remission Kidney function, plasma proteins, cell blood counts, and cholesterol obtained monthly Primary efficacy measure was the percentage change in daily proteinuria at 3 months
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Permutated block randomisation with blocks of variable size
Allocation concealment (selection bias)	Low risk	Allocation was concealed by contacting the holder of the allocation schedule at central administration
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Clinical investigators, study nurses enrolling patients, and the statistician were not blinded to group assignment Study staff responsible for follow up were blinded so their management of patients would not be influenced by treatment allocation
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Study staff responsible for facilitating follow‐up data measurements by contacting patient families by phone were kept blinded Also, as the outcome measured was a laboratory value, lack of blinding is unlikely to affect outcome
Incomplete outcome data (attrition bias) All outcomes	Low risk	No loss to follow‐up All patients analysed; 1 patient from each group did not complete treatment due to adverse side effects
Selective reporting (reporting bias)	High risk	Data on partial remission not included Primary outcome (end study proteinuria) not provided in a form that can be included in meta‐analysis Adverse effects related to RTX were only reported
Other bias	Low risk	Supported by Italian Ministry of Health, the Renal Child Foundation, two other non‐Pharma related foundations