Table 2.
Characteristics of discussed studies of rituximab in IMN
| Study | Study design | Population | Rituximab protocol | Selected outcomes | Results |
|---|---|---|---|---|---|
| Remuzzi et al21 | Prospective, open label, single arm | Eight patients with IMN and urine protein of >3.5 g/day, despite full dose ACEI for 6 months | 375 mg/m2 every 4 weeks for 20 weeks | CR: proteinuria <1 g/day | Two patients achieved complete remission |
| PR: proteinuria <3.5 g | Three patients achieved partial remission | ||||
| Mean proteinuria at 20 weeks | Mean proteinuria decreased from 8.6 to 3.8 g/day | ||||
| Side effects | Transient infusion-related reactions | ||||
| Fervenza et al22 | Prospective, open label, single arm | 15 patients with IMN and severe nephrotic syndrome despite | 1 g on days 1 and 15 | Change in mean proteinuria at 12 months | Mean proteinuria decreased from 13±5.7 to 6±7.3 g/day at 12 months |
| ACEIs or ARBs for 6 months (one lost to follow-up) | Course repeated at 6 months for 3 g and B-cell recovery (ten patients were retreated at 6 months) | CR: proteinuria <3 g/day | 2/14 at 12 months | ||
| PR: proteinuria <3 g/day | 6/14 at 12 months | ||||
| Side effects | Transient infusion-related reactions | ||||
| Ruggenenti et al23 | Prospective, open label, single arm | 100 patients with IMN and proteinuria of >3.5 g/day, despite 6 months of ACEIs | 4 weekly doses of rituximab 375 mg/m2 | Primary outcome: CR or PR defined as 24-hour urine protein excretion <0.3 or 3 g | 65% achieved the primary outcome at 29 months. Median time to remission: 7.1 months |
| Mean proteinuria at baseline was 9.1 (5.8–12.8) | Additional course was given if B-cell recovery | Side effects | No treatment-related adverse events apart from transient infusion reactions | ||
| Segarra et al24 | Prospective, open label, single arm | 13 patients with CNI-dependent IMN and GFR >60 mL/min | 4 weekly doses of rituximab 375 mg/m2 | Percentage of patients who achieved treatment withdrawal | 6 months after rituximab, CNIs and steroids could be withdrawn in all patients with no evidence of relapse |
| Additional course was given if relapse (three patients) | Percentage of patients who maintained CR or PR 30 months after treatment withdrawal | At 30 months, all patients were maintained in remission | |||
| Adverse events | No serious adverse events related to rituximab | ||||
| Dahan et al25 | Prospective, multicenter, randomized, controlled, parallel group trial | 77 patients with IMN and nephrotic syndrome despite 6 months of NIAT | NIAT-rituximab group (intervention): NIAT + rituximab 375 mg/m2 on days 1 and 8 | Primary end point: percentage of patients with CR or PR at 6 months (CR: proteinuria <500 mg/day, PR: proteinuria <3.5 g/day) | No difference in primary end point at 6 months, however, the extended observational phase favored NIAT- rituximab group vs NIAT group: (64.9% vs 34.2% OR, 3.5; 95% CI, 1.7–9.2; P<0.01) |
| NIAT group (control) | Decreased proteinuria of >50% + increase in serum albumin >30% | 41% vs 13%, P<0.01 favoring NIAT- rituximab | |||
| PLA2R-Ab levels | 56% achieved depletion of PLA2R-Ab at 3 months in rituximab group | ||||
| Adverse events | No difference between the two groups |
Abbreviations: ACEIs, angiotensin-converting-enzyme-inhibitors; ARBs, angiotensin-receptor-blockers; CI, confidence interval; CNIs, calcineurin inhibitors; CR, complete remission; GFR, glomerular filtration rate; IMN, idiopathic membranous nephropathy; NIAT, nonimmunosuppressive antiproteinuric treatment; OR, odds ratio; PLA2R-Ab, phospholipase A2 receptor antibodies; PR, partial remission.