Clinical Response and Pattern of B Cell Suppression with Single Low Dose Rituximab in Nephrology

Overview

Journal Kidney360

Specialty Nephrology

Date 2022 Apr 4

PMID 35369364

Authors

Jacob George

Sunu Alex

E T Arun Thomas

Noble Gracious

Nalanda S Vineetha

Sajeev Kumar

Affiliations

Soon will be listed here.

Abstract

Background: There is no consensus regarding dose and frequency of rituximab in nephrology with extrapolation of doses used in treating lymphoproliferative disorders. There are no guidelines on targeting initial and subsequent doses on the basis of CD19 B cells.

Methods: Initially, 100 mg rituximab was given to 42 adults with steroid-dependent nephrotic syndrome (SDNS) and frequently relapsing nephrotic syndrome (FRNS), idiopathic membranous nephropathy (MN), and high-immunologic-risk kidney transplantation. Absolute and percentage levels of CD19 B cells and clinical status were assessed at baseline, days 30, 90, and 180, and at 1 year. Subsequent doses of rituximab were on the basis of CD19 B cell reconstitution and clinical response.

Results: CD19 B cell percentage decreased from 16.3 ± 7.6 to 0.3 ± 0.3 (≤0.001), 1.9 ± 1.7 (≤0.001), and 4.0 ± 4.5 (=0.005) by 30, 90, and 180 days, respectively. Suppression of CD19 B cell count below 1% at days 30, 90, and 180 was seen in 40 of 42 (95.2%), 18 of 42 (42.9%), and 7 of 42 (16.7%) patients, respectively. Of 30 with SDNS and FRNS followed up for 1 year, 29 (96.7%) went into remission at day 30. Remission was sustained in 23 (76.6%) at day 180 and 21 (70%) at 1 year. There was a significant decrease (<0.001) in the dose of steroids needed to maintain remission at 180 days after rituximab (0.27 ± 0.02 mg/kg to 0.02 ± 0.00 mg/kg). CD19 B cell percentage at 90 days correlated with relapse (=0.001; odds ratio 1.42; 95% confidence interval, 1.25 to 2.57). Eighteen (60%) required an additional dose. Of five with MN, four achieved remission by 6 months, which was sustained in three by 1 year. Of the seven kidney transplant recipients, two had antibody-mediated rejections, although CD19 B cells were suppressed even at 1 year.

Conclusions: Low-dose rituximab induces sustained depletion of CD19 B cells for up to 90 days. Its role in preventing relapses in SDNS, FRNS, MN, and rejection needs further study.

Citing Articles

Infection Risk, Mortality, and Hypogammaglobulinemia Prevalence and Associated Factors in Adults Treated with Rituximab: A Tertiary Care Center Experience.

Alhamadh M, Alhowaish T, Mathkour A, Altamimi B, Alheijani S, Alrashid A Clin Pract. 2023; 13(6):1286-1302.

PMID: 37987416 PMC: 10660466. DOI: 10.3390/clinpract13060115.

Initial Preserved Renal Function as a Predictor of Favorable Renal Response to Rituximab in Refractory or Relapsing Lupus Nephritis: A Single-center Cohort Study in Korea.

Choi S, Ahn S, Oh J, Hong S, Lee C, Yoo B J Rheum Dis. 2023; 29(1):22-32.

PMID: 37476702 PMC: 10324915. DOI: 10.4078/jrd.2022.29.1.22.

Successful Treatment of Catastrophic Antiphospholipid Syndrome Using Rituximab: Case Report and Review of the Literature.

Stanescu C, Andronesi A, Jurcut C, Gherghiceanu M, Vornicu A, Burcea F Medicina (Kaunas). 2021; 57(9).

PMID: 34577835 PMC: 8470109. DOI: 10.3390/medicina57090912.

References

Bruzzese V, Pepe J . Unexpected and persistent depletion of B lymphocytes CD20 following a minimum dose of anti-CD20 antibody (Rituximab). Reumatismo. 2010; 61(4):306-8. DOI: 10.4081/reumatismo.2009.306. View

Francois H, Daugas E, Bensman A, Ronco P . Unexpected efficacy of rituximab in multirelapsing minimal change nephrotic syndrome in the adult: first case report and pathophysiological considerations. Am J Kidney Dis. 2006; 49(1):158-61. DOI: 10.1053/j.ajkd.2006.10.015. View

Anolik J, Campbell D, Felgar R, Young F, Sanz I, Rosenblatt J . The relationship of FcgammaRIIIa genotype to degree of B cell depletion by rituximab in the treatment of systemic lupus erythematosus. Arthritis Rheum. 2003; 48(2):455-9. DOI: 10.1002/art.10764. View

Fervenza F, Abraham R, Erickson S, Valentina Irazabal M, Eirin A, Specks U . Rituximab therapy in idiopathic membranous nephropathy: a 2-year study. Clin J Am Soc Nephrol. 2010; 5(12):2188-98. PMC: 2994079. DOI: 10.2215/CJN.05080610. View

Sood P, Hariharan S . Anti-CD20 Blocker Rituximab in Kidney Transplantation. Transplantation. 2017; 102(1):44-58. DOI: 10.1097/TP.0000000000001849. View

Fernandez-Fresnedo G, Segarra A, Gonzalez E, Alexandru S, Delgado R, Ramos N . Rituximab treatment of adult patients with steroid-resistant focal segmental glomerulosclerosis. Clin J Am Soc Nephrol. 2009; 4(8):1317-23. PMC: 2723972. DOI: 10.2215/CJN.00570109. View

Weidenbusch M, Rommele C, Schrottle A, Anders H . Beyond the LUNAR trial. Efficacy of rituximab in refractory lupus nephritis. Nephrol Dial Transplant. 2012; 28(1):106-11. DOI: 10.1093/ndt/gfs285. View

Smith K, Jones R, Burns S, Jayne D . Long-term comparison of rituximab treatment for refractory systemic lupus erythematosus and vasculitis: Remission, relapse, and re-treatment. Arthritis Rheum. 2006; 54(9):2970-82. DOI: 10.1002/art.22046. View

Kranick S, Mowry E, Rosenfeld M . Progressive multifocal leukoencephalopathy after rituximab in a case of non-Hodgkin lymphoma. Neurology. 2007; 69(7):704-6. DOI: 10.1212/01.wnl.0000267325.06000.d9. View

10.

Maxted A, Dalrymple R, Chisholm D, McColl J, Tse Y, Christian M . Low-dose rituximab is no less effective for nephrotic syndrome measured by 12-month outcome. Pediatr Nephrol. 2018; 34(5):855-863. PMC: 6424916. DOI: 10.1007/s00467-018-4172-3. View

11.

Salant D . Does Epitope Spreading Influence Responsiveness to Rituximab in PLA2R-Associated Membranous Nephropathy?. Clin J Am Soc Nephrol. 2019; 14(8):1122-1124. PMC: 6682826. DOI: 10.2215/CJN.07300619. View

12.

Seitz-Polski B, Dolla G, Payre C, Girard C, Polidori J, Zorzi K . Epitope Spreading of Autoantibody Response to PLA2R Associates with Poor Prognosis in Membranous Nephropathy. J Am Soc Nephrol. 2015; 27(5):1517-33. PMC: 4849812. DOI: 10.1681/ASN.2014111061. View

13.

Vo A, Lukovsky M, Toyoda M, Wang J, Reinsmoen N, Lai C . Rituximab and intravenous immune globulin for desensitization during renal transplantation. N Engl J Med. 2008; 359(3):242-51. DOI: 10.1056/NEJMoa0707894. View

14.

Hogan J, Dossier C, Kwon T, Macher M, Maisin A, Couderc A . Effect of different rituximab regimens on B cell depletion and time to relapse in children with steroid-dependent nephrotic syndrome. Pediatr Nephrol. 2018; 34(2):253-259. DOI: 10.1007/s00467-018-4052-x. View

15.

Ruggenenti P, Chiurchiu C, Abbate M, Perna A, Cravedi P, Bontempelli M . Rituximab for idiopathic membranous nephropathy: who can benefit?. Clin J Am Soc Nephrol. 2007; 1(4):738-48. DOI: 10.2215/CJN.01080905. View

16.

Lee J, Park J, Kim D, Lee J, Kim B, Kim M . Effects of rituximab dose on hepatitis B reactivation in patients with resolved infection undergoing immunologic incompatible kidney transplantation. Sci Rep. 2018; 8(1):15629. PMC: 6199240. DOI: 10.1038/s41598-018-34111-5. View

17.

Kamei K, Ishikura K, Sako M, Aya K, Tanaka R, Nozu K . Long-term outcome of childhood-onset complicated nephrotic syndrome after a multicenter, double-blind, randomized, placebo-controlled trial of rituximab. Pediatr Nephrol. 2017; 32(11):2071-2078. DOI: 10.1007/s00467-017-3718-0. View

18.

Ruggenenti P, Ruggiero B, Cravedi P, Vivarelli M, Massella L, Marasa M . Rituximab in steroid-dependent or frequently relapsing idiopathic nephrotic syndrome. J Am Soc Nephrol. 2014; 25(4):850-63. PMC: 3968490. DOI: 10.1681/ASN.2013030251. View

19.

Charles P, Terrier B, Perrodeau E, Cohen P, Faguer S, Huart A . Comparison of individually tailored versus fixed-schedule rituximab regimen to maintain ANCA-associated vasculitis remission: results of a multicentre, randomised controlled, phase III trial (MAINRITSAN2). Ann Rheum Dis. 2018; 77(8):1143-1149. DOI: 10.1136/annrheumdis-2017-212878. View

20.

Benz K, Dotsch J, Rascher W, Stachel D . Change of the course of steroid-dependent nephrotic syndrome after rituximab therapy. Pediatr Nephrol. 2004; 19(7):794-7. DOI: 10.1007/s00467-004-1434-z. View