Ponticelli 1992.

Study characteristics
Methods	Study design: parallel, open‐label RCT Study duration: before December 1989 Duration of follow‐up: 4 years*
Participants	Setting: multicentre (Italian Idiopathic Membranous Nephropathy Treatment Study Group) Country: Italy Inclusion criteria: biopsy‐proven IMN with nephrotic syndrome Baseline characteristics Pathology stage (I‐II/III‐IV): treatment group 1 (27/18); treatment group 2 (29/18) Mean proteinuria ± SD (g/24 hours): treatment group 1 (7.6 ± 4.2); treatment group 2 (7.0 ± 4.1) Hypertension: treatment group 1 (15/45); treatment group 2 (14/47) SCr (mg/dL): treatment group 1 (1.0 ± 0.3); treatment group 2 (1.0 ± 0.3) Baseline declining kidney function: no, patients with SCr > 1.7 mg/dL (150 μmol/L) were excluded Use of ACEi or ARB during follow‐up: not reported Previous immunosuppressive status: patients with previous treatment with corticosteroids or cytotoxic agents were excluded Number: treatment group 1 (45); treatment group 2 (47) Mean age, range (years): treatment group 1 (46, 14‐65); treatment group 2 (47, 14‐64) Sex (M/F): treatment group 1 (32/13); treatment group 2 (27/20) Exclusion criteria: aged < 14 and > 65 years; SCr > 1.7 mg/dL; previous treatment with corticosteroids or cytotoxic agents; positive for anti‐DNA antibodies, hepatitis B antigen or Venereal Disease Research Laboratory test; low C3 or C4; DM; infection; exposure to drugs that could induce IMN
Interventions	Treatment group 1 Methylprednisolone: 3 cycles (IV) of 1 g on 3 consecutive days and then 0.4 mg/kg/day given orally for 27 days, in a single morning dose Chlorambucil (oral): 0.2 mg/kg/day Treatment group 2 Methylprednisolone (IV): 1 g on 3 consecutive days at the beginning of treatment and again 2 and 4 months Methylprednisolone (oral): 0.4 mg/kg every other day, except during the period of IV administration, for six months
Outcomes	Death ESKD 50% or 100% SCr increase Final SCr Remission (complete and partial) Final proteinuria Side effects leading to patient withdrawal or hospitalisation Follow‐up time points: 1, 2, 3, and 4 years
Notes	Funding source: not reported *Duration of follow‐up treatment group 1 (54 ± 16 months); treatment group 2 (54 ± 17 months). 63/92 (68%) patients completed the 48‐month follow‐up and were analysed for the outcomes of partial or complete remission (treatment group 1 (32/45, 71%), treatment group 2 (31/47, 66%). 50/92 (54%) patients had data for final proteinuria at 48 months (treatment group 1 (26/45, 58%); treatment group 2 24/47 (51%))
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	The coordinating centre assigned the patients consecutively to one of the two treatment regimens in random order
Allocation concealment (selection bias)	Low risk	Central randomisation method described could not allow investigators/participants to know or influence intervention group before eligible participant entered in the study
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open‐label study
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Insufficient information to permit judgement
Incomplete outcome data (attrition bias) All outcomes	Low risk	Patients who could not complete treatment were included in the analysis according to the intention‐to‐treat principle. For the two patients who died and the one who was lost to follow‐up, data obtained at the last observation were considered
Selective reporting (reporting bias)	Low risk	The study protocol was not available but it was clear that the published reports included all expected outcomes, including those that were pre‐specified
Other bias	Low risk	The study appeared to be free of other sources of bias