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

被引:123
作者
Mendez, Liliana Michelle Gomez [1 ]
Cascino, Matthew D. [2 ]
Garg, Jay [2 ]
Katsumoto, Tamiko R. [2 ]
Brakeman, Paul [1 ]
Dall'Era, Maria [1 ]
Looney, Richard John [3 ]
Rovin, Brad [4 ]
Dragone, Leonard [2 ]
Brunetta, Paul [2 ]
机构
[1] Univ Calif San Francisco, San Francisco, CA 94143 USA
[2] Genentech Inc, 460 Point San Bruno Blvd, San Francisco, CA 94080 USA
[3] Rochester Univ, Rochester, NY USA
[4] Ohio State Univ, Columbus, OH 43210 USA
来源
CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY | 2018年 / 13卷 / 10期
关键词
lupus nephritis; rituximab; b cell depletion; LUNAR; renal response; systemic lupus erythematosus; RHEUMATOID-ARTHRITIS; TUBULOINTERSTITIAL INFLAMMATION; ANTI-CD20; ANTIBODY; THERAPY; EFFICACY; ERYTHEMATOSUS; OBINUTUZUMAB; DISEASE; MECHANISMS; EFFICIENCY;
D O I
10.2215/CJN.01070118
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
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/mu 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/mu 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.
引用
收藏
页码:1502 / 1509
页数:8
相关论文
共 41 条
[1]   Anti-Sm is associated with the early poor outcome of lupus nephritis [J].
Ahn, Sung Soo ;
Yoo, Byung-Woo ;
Song, Jason Jungsik ;
Park, Yong-Beom ;
Lee, Soo-Kon ;
Lee, Sang-Won .
INTERNATIONAL JOURNAL OF RHEUMATIC DISEASES, 2016, 19 (09) :897-902
[2]   Depletion of B cells in murine lupus: Efficacy and resistance [J].
Ahuja, Anupama ;
Shupe, Jonathan ;
Dunn, Robert ;
Kashgarian, Michael ;
Kehry, Marilyn R. ;
Shlomchik, Mark J. .
JOURNAL OF IMMUNOLOGY, 2007, 179 (05) :3351-3361
[3]   An Acquired Defect in IgG-Dependent Phagocytosis Explains the Impairment in Antibody-Mediated Cellular Depletion in Lupus [J].
Ahuja, Anupama ;
Teichmann, Lino L. ;
Wang, Haowei ;
Dunn, Robert ;
Kehry, Marilyn R. ;
Shlomchik, Mark J. .
JOURNAL OF IMMUNOLOGY, 2011, 187 (07) :3888-3894
[4]   Variability in the biological response to anti-CD20 B cell depletion in systemic lupus erythaematosus [J].
Albert, D. ;
Dunham, J. ;
Khan, S. ;
Stansberry, J. ;
Kolasinski, S. ;
Tsai, D. ;
Pullman-Mooar, S. ;
Barnack, F. ;
Striebich, C. ;
Looney, R. J. ;
Prak, E. T. Luning ;
Kimberly, R. ;
Zhang, Y. ;
Eisenberg, R. .
ANNALS OF THE RHEUMATIC DISEASES, 2008, 67 (12) :1724-1731
[5]   Clinical associations of anti-Smith antibodies in PROFILE: a multi-ethnic lupus cohort [J].
Arroyo-Avila, Mariangeli ;
Santiago-Casas, Yesenia ;
McGwin, Gerald, Jr. ;
Cantor, Ryan S. ;
Petri, Michelle ;
Ramsey-Goldman, Rosalind ;
Reveille, John D. ;
Kimberly, Robert P. ;
Alarcon, Graciela S. ;
Vila, Luis M. ;
Brown, Elizabeth E. .
CLINICAL RHEUMATOLOGY, 2015, 34 (07) :1217-1223
[6]   Prolonged Effects of Short-Term Anti-CD20 B Cell Depletion Therapy in Murine Systemic Lupus Erythematosus [J].
Bekar, Kai W. ;
Owen, Teresa ;
Dunn, Robert ;
Ichikawa, Travis ;
Wang, Wensheng ;
Wang, Roger ;
Barnard, Jennifer ;
Brady, Sean ;
Nevarez, Sarah ;
Goldman, Bruce I. ;
Kehry, Marilyn ;
Anolik, Jennifer H. .
ARTHRITIS AND RHEUMATISM, 2010, 62 (08) :2443-2457
[7]   Monocyte Subsets Responsible for Immunoglobulin G-Dependent Effector Functions In Vivo [J].
Biburger, Markus ;
Aschermann, Susanne ;
Schwab, Inessa ;
Lux, Anja ;
Albert, Heike ;
Danzer, Heike ;
Woigk, Melissa ;
Dudziak, Diana ;
Nimmerjahn, Falk .
IMMUNITY, 2011, 35 (06) :932-944
[8]  
Cassese G, 2001, EUR J IMMUNOL, V31, P2726, DOI 10.1002/1521-4141(200109)31:9<2726::AID-IMMU2726>3.0.CO
[9]  
2-H
[10]   In Situ B Cell-Mediated Immune Responses and Tubulointerstitial Inflammation in Human Lupus Nephritis [J].
Chang, Anthony ;
Henderson, Scott G. ;
Brandt, Daniel ;
Liu, Ni ;
Guttikonda, Riteesha ;
Hsieh, Christine ;
Kaverina, Natasha ;
Utset, Tammy O. ;
Meehan, Shane M. ;
Quigg, Richard J. ;
Meffre, Eric ;
Clark, Marcus R. .
JOURNAL OF IMMUNOLOGY, 2011, 186 (03) :1849-1860