Clinical Journal of the American Society of Nephrology · 2018 · 183 citations · 34 references
Life SciencesImmunologyPharmacotherapyAutoimmunityImmunopathologyRheumatologyB Cell BiologyB-cell ResponsesHumoral ImmunityImmune-mediated Renal DiseaseRenal DiseaseRenal Function TestsB-cell Depleting AgentsB-cell Mediated Renal AutoimmunityComplete Response AssessmentInadequate TreatmentLogistic RegressionLupus Nephritis TherapyProtein-to-creatinine RatioSerum Creatinine Assessment
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/ µ l, 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/ µ l) 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
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