Comparison of Obinutuzumab and Rituximab for Treating Primary Membranous Nephropathy

Abstract

Key Points:

1. Obinutuzumab induced more remission than rituximab at 12 months in patients with primary membranous nephropathy.

2. Obinutuzumab shared a similar safety profile as rituximab in patients with primary membranous nephropathy.

Background: This study compared the effectiveness and safety profiles of obinutuzumab and rituximab in the treatment of patients with primary membranous nephropathy (MN).

Methods: Patients with primary MN who had urine protein ≥3.5 g/24 hours and eGFR ≥30 ml/min per 1.73 m² despite 6 months of angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker and treatment with obinutuzumab or rituximab were included and matched by propensity score (ratio: 1:2) on the basis of age, sex, urine protein, eGFR, and titers of Anti-Phospholipase A2 receptor (PLA2R) antibody. The primary outcome was defined as a combination of partial or complete remission at 12 months. Logistic regression models, Kaplan–Meier curves, and absolute risk differences were used to compare the therapeutic effectiveness and safety profiles of obinutuzumab and rituximab.

Results: Sixty-three patients with primary MN were included in the study, with 21 patients receiving obinutuzumab and 42 patients receiving rituximab. At 12 months, the primary outcome was achieved in 20 of 21 patients in the obinutuzumab group and 28 of 42 patients in the rituximab group (obinutuzumab versus rituximab: 95% versus 67%; odds ratio, 10.00; 95% confidence intervals, 1.21 to 82.35; P = 0.03). Moreover, patients in the obinutuzumab group acquired more complete remission (obinutuzumab versus rituximab: 38% versus 14%; odds ratio, 3.69; 95% confidence interval, 1.08 to 12.68; P = 0.04). In PLA2R-associated primary MN subgroup analyses, patients in the obinutuzumab group sustained lower CD19 B-cell counts (CD19 B-cell counts: median [interquartile range] 0 [0–6] cells/μl versus 20 [3–58] cells/μl, P = 0.002) and were more prone to achieve immunological remission (defined as PLA2R antibody <2 RU/ml) at 6 months (obinutuzumab versus rituximab: 92% [12 out of 13] versus 64% [16 out of 25], P = 0.06) than rituximab. Both treatment regimens were well tolerated.

Conclusions: Our study demonstrated that obinutuzumab is associated with higher odds of clinical remission compared with rituximab at 12 months, which may be due to higher immunological remission at 6 months with a similar safety profile in patients with primary MN.

Graphical abstract

Figure 1

Flow chart of the study. PSM, propensity score matching. ACEI/ARB, angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker; RTX, rituximab.

Figure 2

Comparison between rituximab and obinutuzumab in a Kaplan–Meier curve. (A) For remission defined as a combination of partial remission and complete remission: remission time: obinutuzumab versus rituximab: 5 (95% CI, 3.52 to 6.48) months versus 6 (95% CI, 3.66 to 8.34) months; 12-month cumulative remission percentiles (95% CI): 0.95 (95% CI, 0.81 to 0.99) versus 0.71 (95% CI, 0.58 to 0.85), P = 0.09. (B) For complete remission: 12-month cumulative complete remission: 0.38 (0.17 to 0.59) versus 0.14 (95% CI, 0.04 to 0.25), P = 0.04; red line for obinutuzumab, black line for rituximab. CI, confidence interval.

Figure 3

Comparison of urine protein, serum albumin, and eGFR between rituximab and obinutuzumab in the whole cohort. (A) Comparison of urine protein between rituximab and obinutuzumab. (B) Comparison of serum albumin between rituximab and obinutuzumab. (C) Comparison of eGFR between rituximab and obinutuzumab. * P < 0.05.

Figure 4

Comparison of immunological remission rates in PLA2R-associated MN between two regimens (PLA2R antibody available in 13 patients on obinutuzumab and 25 on rituximab at 6 months; PLA2R antibody available in 15 patients on obinutuzumab and 30 on rituximab at 12 months). (A) Comparison of PLA2R antibody <14 RU/ml rates at 6 and 12 months: 6 months: obinutuzumab versus rituximab: 100% (13 of 13) versus 80% (20 of 25), P = 0.14, absolute risk difference (95% CI): 0.20 (95% CI, −0.05 to 0.39). Twelve months: obinutuzumab versus rituximab: 100% (15 of 15) versus 83% (25 of 30), P = 0.15, absolute risk difference (95% CI): 0.17 (95% CI, −0.06 to 0.34). (B) Comparison of immunological remission (defined as PLA2R antibody <2 RU/ml) rates at 6 and 12 months: 6 months: obinutuzumab versus rituximab: 92% (12 of 13) versus 64% (16 of 25), P = 0.06, absolute risk difference (95% CI): 0.28 (95% CI, −0.02 to 0.49). Twelve months: obinutuzumab versus rituximab: 93% (14 of 15) versus 73% (22 of 30), P = 0.11, absolute risk difference (95% CI): 0.20 (95% CI, −0.06 to 0.39). (C) Comparison of B-cell depletion rate at 6 months between two regimens: obinutuzumab versus rituximab: B-cell depletion: 10 of 13 (77%) versus 10 of 31 (32%), P = 0.01. (D) Comparison of B-cell counts at 6 months between patients with remission at 12 months and without remission at 12 months in PLA2R-associated MN: 3.25 (0–40.25) μl versus 38.5 (10.75–69.25) μl, P = 0.04. Red line for median, blue line for IQR. IQR, interquartile range; MN, membranous nephropathy; PLA2R, anti-phospholipase A2 receptor.