Peripheral Blood B Cell Depletion after Rituximab and Complete Response in Lupus Nephritis

Abstract

Background and objectives: Incomplete peripheral blood B cell depletion after rituximab in lupus nephritis might correlate with inability to reduce tubulointerstitial lymphoid aggregates in the kidney, which together could be responsible for inadequate response to treatment. We utilized data from the Lupus Nephritis Assessment with Rituximab (LUNAR) study to characterize the variability of peripheral blood B cell depletion after rituximab and assess its association with complete response in patients with lupus nephritis.

Design, setting, participants, & measurements: We analyzed 68 participants treated with rituximab. Peripheral blood B cell depletion was defined as 0 cells/µl, termed "complete peripheral depletion," assessed over 78 weeks. Logistic regression was used to estimate the association between characteristics of complete peripheral depletion and complete response (defined as urine protein-to-creatinine ratio <0.5 mg/mg, and normal serum creatinine or an increase in creatinine <15%, if normal at baseline), assessed at week 78.

Results: A total of 53 (78%) participants achieved complete peripheral depletion (0 cells/µl) in a median time of 182 days (interquartile range, 80-339).The median duration of complete peripheral depletion was 71 days (interquartile range, 14-158). Twenty-five (47%) participants with complete peripheral depletion achieved complete response, compared with two (13%) without. Complete peripheral depletion was associated with complete response (unadjusted odds ratio [OR], 5.8; 95% confidence interval [95% CI], 1.2 to 28; P=0.03). Longer time to achieving complete peripheral depletion was associated with a lower likelihood of complete response (unadjusted OR, 0.89; 95% CI, 0.81 to 0.98; P=0.02). Complete peripheral depletion lasting >71 days (the median) was associated with complete response (unadjusted OR, 4.1; 95% CI, 1.5 to 11; P=0.008).

Conclusions: There was substantial variability in peripheral blood B cell depletion in patients with lupus nephritis treated with rituximab from the LUNAR trial. Achievement of complete peripheral depletion, as well as the rapidity and duration of complete peripheral depletion, were associated with complete response at week 78.

Podcast: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2018_09_06_CJASNPodcast_18_10_.mp3.

Trial registration: ClinicalTrials.gov NCT00282347.

Keywords: LUNAR; b cell depletion; lupus nephritis; renal response; rituximab; systemic lupus erythematosus.

Copyright © 2018 by the American Society of Nephrology.

Figures

Graphical abstract

Figure 1.

A larger percentage of participants from the LUNAR trial who achieved complete peripheral depletion (n = 53) achieved complete response at week 52 and at week 78, compared to participants who did not achieve peripheral depletion (n = 15).

Figure 2.

Kaplan Meier graphs demonstrating wide variability in time to complete peripheral depletion and in time to complete response in participants treated with rituximab from the LUNAR trial. (A) Time to complete peripheral depletion, in days. Line denotes day 365, which is the last day that participants ever achieved CD19 of 0 cells/µl. (B) Cumulative incidence of complete response up to week 78, in days.