Rituximab therapy in idiopathic membranous nephropathy: A 2-year study

Fernando Custodio Fervenza, Roshini S. Abraham, Stephen B. Erickson, Maria Irazabal Mira, Alfonso Eirin, Ulrich Specks, Patrick H. Nachman, Eric J. Bergstralh, Nelson Leung, Fernando G Cosio, Marie C Hogan, John J. Dillon, LaTonya Hickson, Xujian Li, Daniel C. Cattran

Research output: Contribution to journalArticle

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Abstract

Background and objectives: It was postulated that in patients with membranous nephropathy (MN), four weekly doses of Rituximab (RTX) would result in more effective B cell depletion, a higher remission rate, and maintaining the same safety profile compared with patients treated with RTX dosed at 1 g every 2 weeks. This hypothesis was supported by previous pharmacokinetic (PK) analysis showing that RTX levels in the two-dose regimen were 50% lower compared with nonproteinuric patients, which could potentially result in undertreatment. Design, setting, participants, & measurements: Twenty patients with MN and proteinuria >5 g/24 h received RTX (375 mg/m2 x 4), with re-treatment at 6 months regardless of proteinuria response. PK analysis was conducted simultaneously with immunological analyses of T and B cells to ascertain the effect of RTX on lymphocyte subpopulations. Results: Baseline proteinuria of 11.9 g/24 h decreased to 4.2 and 2.0 g/24 h at 12 and 24 months, respectively, whereas creatinine clearance increased from 72.4 ml/min per 1.73 m2 at baseline to 88.4 ml/min per 1.73 m2 at 24 months. Of 18 patients who completed 24-month follow-up, 4 are in complete remission, 12 are in partial remission, 1 has a limited response, and 1 patient relapsed. Serum RTX levels were similar to those obtained with two doses of RTX. Conclusions: Four doses of RTX resulted in more effective B cell depletion, but proteinuria reduction was similar to RTX at 1 g every 2 weeks. Baseline quantification of lymphocyte subpopulations did not predict response to RTX therapy.

Original languageEnglish (US)
Pages (from-to)2188-2198
Number of pages11
JournalClinical Journal of the American Society of Nephrology
Volume5
Issue number12
DOIs
StatePublished - Dec 1 2010

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Membranous Glomerulonephritis
varespladib methyl
Proteinuria
Therapeutics
B-Lymphocytes
Lymphocyte Subsets
Pharmacokinetics
Rituximab
Creatinine
T-Lymphocytes
Safety

ASJC Scopus subject areas

  • Nephrology
  • Transplantation
  • Epidemiology
  • Critical Care and Intensive Care Medicine

Cite this

Rituximab therapy in idiopathic membranous nephropathy : A 2-year study. / Fervenza, Fernando Custodio; Abraham, Roshini S.; Erickson, Stephen B.; Irazabal Mira, Maria; Eirin, Alfonso; Specks, Ulrich; Nachman, Patrick H.; Bergstralh, Eric J.; Leung, Nelson; Cosio, Fernando G; Hogan, Marie C; Dillon, John J.; Hickson, LaTonya; Li, Xujian; Cattran, Daniel C.

In: Clinical Journal of the American Society of Nephrology, Vol. 5, No. 12, 01.12.2010, p. 2188-2198.

Research output: Contribution to journalArticle

Fervenza, Fernando Custodio ; Abraham, Roshini S. ; Erickson, Stephen B. ; Irazabal Mira, Maria ; Eirin, Alfonso ; Specks, Ulrich ; Nachman, Patrick H. ; Bergstralh, Eric J. ; Leung, Nelson ; Cosio, Fernando G ; Hogan, Marie C ; Dillon, John J. ; Hickson, LaTonya ; Li, Xujian ; Cattran, Daniel C. / Rituximab therapy in idiopathic membranous nephropathy : A 2-year study. In: Clinical Journal of the American Society of Nephrology. 2010 ; Vol. 5, No. 12. pp. 2188-2198.
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T1 - Rituximab therapy in idiopathic membranous nephropathy

T2 - A 2-year study

AU - Fervenza, Fernando Custodio

AU - Abraham, Roshini S.

AU - Erickson, Stephen B.

AU - Irazabal Mira, Maria

AU - Eirin, Alfonso

AU - Specks, Ulrich

AU - Nachman, Patrick H.

AU - Bergstralh, Eric J.

AU - Leung, Nelson

AU - Cosio, Fernando G

AU - Hogan, Marie C

AU - Dillon, John J.

AU - Hickson, LaTonya

AU - Li, Xujian

AU - Cattran, Daniel C.

PY - 2010/12/1

Y1 - 2010/12/1

N2 - Background and objectives: It was postulated that in patients with membranous nephropathy (MN), four weekly doses of Rituximab (RTX) would result in more effective B cell depletion, a higher remission rate, and maintaining the same safety profile compared with patients treated with RTX dosed at 1 g every 2 weeks. This hypothesis was supported by previous pharmacokinetic (PK) analysis showing that RTX levels in the two-dose regimen were 50% lower compared with nonproteinuric patients, which could potentially result in undertreatment. Design, setting, participants, & measurements: Twenty patients with MN and proteinuria >5 g/24 h received RTX (375 mg/m2 x 4), with re-treatment at 6 months regardless of proteinuria response. PK analysis was conducted simultaneously with immunological analyses of T and B cells to ascertain the effect of RTX on lymphocyte subpopulations. Results: Baseline proteinuria of 11.9 g/24 h decreased to 4.2 and 2.0 g/24 h at 12 and 24 months, respectively, whereas creatinine clearance increased from 72.4 ml/min per 1.73 m2 at baseline to 88.4 ml/min per 1.73 m2 at 24 months. Of 18 patients who completed 24-month follow-up, 4 are in complete remission, 12 are in partial remission, 1 has a limited response, and 1 patient relapsed. Serum RTX levels were similar to those obtained with two doses of RTX. Conclusions: Four doses of RTX resulted in more effective B cell depletion, but proteinuria reduction was similar to RTX at 1 g every 2 weeks. Baseline quantification of lymphocyte subpopulations did not predict response to RTX therapy.

AB - Background and objectives: It was postulated that in patients with membranous nephropathy (MN), four weekly doses of Rituximab (RTX) would result in more effective B cell depletion, a higher remission rate, and maintaining the same safety profile compared with patients treated with RTX dosed at 1 g every 2 weeks. This hypothesis was supported by previous pharmacokinetic (PK) analysis showing that RTX levels in the two-dose regimen were 50% lower compared with nonproteinuric patients, which could potentially result in undertreatment. Design, setting, participants, & measurements: Twenty patients with MN and proteinuria >5 g/24 h received RTX (375 mg/m2 x 4), with re-treatment at 6 months regardless of proteinuria response. PK analysis was conducted simultaneously with immunological analyses of T and B cells to ascertain the effect of RTX on lymphocyte subpopulations. Results: Baseline proteinuria of 11.9 g/24 h decreased to 4.2 and 2.0 g/24 h at 12 and 24 months, respectively, whereas creatinine clearance increased from 72.4 ml/min per 1.73 m2 at baseline to 88.4 ml/min per 1.73 m2 at 24 months. Of 18 patients who completed 24-month follow-up, 4 are in complete remission, 12 are in partial remission, 1 has a limited response, and 1 patient relapsed. Serum RTX levels were similar to those obtained with two doses of RTX. Conclusions: Four doses of RTX resulted in more effective B cell depletion, but proteinuria reduction was similar to RTX at 1 g every 2 weeks. Baseline quantification of lymphocyte subpopulations did not predict response to RTX therapy.

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