Efficacy of rituximab and plasma exchange in antineutrophil cytoplasmic antibody-associated vasculitis with severe kidney disease

Marta Casal Moura; Maria V. Irazabal; Alfonso Eirin; Ladan Zand; Sanjeev Sethi; Bijan J. Borah; Jeffrey L. Winters; James P. Moriarty; Rodrigo Cartin-Ceba; Alvise Berti; Misbah Baqir; Gwen E. Thompson; Ashima Makol; Kenneth J. Warrington; Viengneesee Thao; Ulrich Specks; Fernando C. Fervenza

doi:10.1681/ASN.2019111197

Efficacy of rituximab and plasma exchange in antineutrophil cytoplasmic antibody-associated vasculitis with severe kidney disease

Marta Casal Moura, Maria V. Irazabal, Alfonso Eirin, Ladan Zand, Sanjeev Sethi, Bijan J. Borah, Jeffrey L. Winters, James P. Moriarty, Rodrigo Cartin-Ceba, Alvise Berti, Misbah Baqir, Gwen E. Thompson, Ashima Makol, Kenneth J. Warrington, Viengneesee Thao, Ulrich Specks, Fernando C. Fervenza

Medicine - Renal and Hypertension Division

Research output: Contribution to journal › Article › peer-review

51 Scopus citations

Abstract

BACKGROUND: Treatment of patients with ANCA-associated vasculitis (AAV) and severe renal involvement is not established. We describe outcomes in response to rituximab (RTX) versus cyclophosphamide (CYC) and plasma exchange (PLEX).

METHODS: A retrospective cohort study of MPO- or PR3-ANCA-positive patients with AAV (MPA and GPA) and severe kidney disease (eGFR <30 ml/min per 1.73 m 2). Remission, relapse, ESKD and death after remission-induction with CYC or RTX, with or without the use of PLEX, were compared.

RESULTS: Of 467 patients with active renal involvement, 251 had severe kidney disease. Patients received CYC ( n=161) or RTX ( n=64) for remission-induction, and 51 were also treated with PLEX. Predictors for ESKD and/or death at 18 months were eGFR <15 ml/min per 1.73 m 2 at diagnosis (IRR 3.09 [95% CI 1.49 to 6.40], P=0.002), renal recovery (IRR 0.27 [95% CI 0.12 to 0.64], P=0.003) and renal remission at 6 months (IRR 0.40 [95% CI 0.18 to 0.90], P=0.027). RTX was comparable to CYC in remission-induction (BVAS/WG=0) at 6 months (IRR 1.37 [95% CI 0.91 to 2.08], P=0.132). Addition of PLEX showed no benefit on remission-induction at 6 months (IRR 0.73 [95% CI 0.44 to 1.22], P=0.230), the rate of ESKD and/or death at 18 months (IRR 1.05 [95% CI 0.51 to 2.18], P=0.891), progression to ESKD (IRR 1.06 [95% CI 0.50 to 2.25], P=0.887), and survival at 24 months (IRR 0.54 [95% CI 0.16 to 1.85], P=0.330).

CONCLUSIONS: The apparent benefits and risks of using CYC or RTX for the treatment of patients with AAV and severe kidney disease are balanced. The addition of PLEX to standard remission-induction therapy showed no benefit in our cohort. A randomized controlled trial is the only satisfactory means to evaluate efficacy of remission-induction treatments in AAV with severe renal involvement.

Original language	English (US)
Pages (from-to)	2688-2704
Number of pages	17
Journal	Journal of the American Society of Nephrology
Volume	31
Issue number	11
DOIs	https://doi.org/10.1681/ASN.2019111197
State	Published - Nov 2020

Bibliographical note

Funding Information:
Dr. Marta Casal Moura, Dr. Ulrich Specks, and Dr. Fernando C. Fervenza designed the study. Dr. Marta Casal Moura, Dr. Maria V. Irazabal, and Dr. Alfonso Eirin abstracted the data. Dr. Marta Casal Moura, Dr. Sanjeev Sethi, Dr. Ulrich Specks, and Dr. Fernando C. Fervenza analyzed the data. Dr. Marta Casal Moura, Dr. Bijan J. Borah, Mr. James P. Moriarty, and Miss Viengneesee Thao performed the statistical analysis. Dr. Marta Casal Moura, Dr. Ladan Zand, Dr. Ulrich Specks, and Dr. Fernando C. Fervenza drafted and revised the paper. All authors provided input for the final version of the manuscript. Dr. Fernando C. Fervenza received unrestricted grants from Genentech Inc., South San Francisco, CA, outside the submitted work. Dr. Ulrich Specks reports grants from Genentech, grants from Bristol Myer Squibb, grants and personal fees from ChemoCentryx, grants from GSK, grants and other from AstraZeneca, and other from InsMed, outside the submitted work. Dr. Kenneth Warrington reports grants from Eli Lilly, grants from Roche/Genentech, grants from GlaxoSmithKline, grants from Kiniksa, personal fees from Roche/ Genentech, and personal fees from Sanofi, outside the submitted work.

Funding Information:
The study was supported by an internal grant from the Mayo Nephrology Collaborative Group, Mayo Foundation.

Publisher Copyright:
Copyright © 2020 by the American Society of Nephrology

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Moura, M. C., Irazabal, M. V., Eirin, A., Zand, L., Sethi, S., Borah, B. J., Winters, J. L., Moriarty, J. P., Cartin-Ceba, R., Berti, A., Baqir, M., Thompson, G. E., Makol, A., Warrington, K. J., Thao, V., Specks, U., & Fervenza, F. C. (2020). Efficacy of rituximab and plasma exchange in antineutrophil cytoplasmic antibody-associated vasculitis with severe kidney disease. Journal of the American Society of Nephrology, 31(11), 2688-2704. https://doi.org/10.1681/ASN.2019111197

Moura, MC, Irazabal, MV, Eirin, A, Zand, L, Sethi, S, Borah, BJ, Winters, JL, Moriarty, JP, Cartin-Ceba, R, Berti, A, Baqir, M, Thompson, GE, Makol, A, Warrington, KJ, Thao, V, Specks, U & Fervenza, FC 2020, 'Efficacy of rituximab and plasma exchange in antineutrophil cytoplasmic antibody-associated vasculitis with severe kidney disease', Journal of the American Society of Nephrology, vol. 31, no. 11, pp. 2688-2704. https://doi.org/10.1681/ASN.2019111197

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title = "Efficacy of rituximab and plasma exchange in antineutrophil cytoplasmic antibody-associated vasculitis with severe kidney disease",

abstract = "BACKGROUND: Treatment of patients with ANCA-associated vasculitis (AAV) and severe renal involvement is not established. We describe outcomes in response to rituximab (RTX) versus cyclophosphamide (CYC) and plasma exchange (PLEX).METHODS: A retrospective cohort study of MPO- or PR3-ANCA-positive patients with AAV (MPA and GPA) and severe kidney disease (eGFR <30 ml/min per 1.73 m 2). Remission, relapse, ESKD and death after remission-induction with CYC or RTX, with or without the use of PLEX, were compared. RESULTS: Of 467 patients with active renal involvement, 251 had severe kidney disease. Patients received CYC ( n=161) or RTX ( n=64) for remission-induction, and 51 were also treated with PLEX. Predictors for ESKD and/or death at 18 months were eGFR <15 ml/min per 1.73 m 2 at diagnosis (IRR 3.09 [95% CI 1.49 to 6.40], P=0.002), renal recovery (IRR 0.27 [95% CI 0.12 to 0.64], P=0.003) and renal remission at 6 months (IRR 0.40 [95% CI 0.18 to 0.90], P=0.027). RTX was comparable to CYC in remission-induction (BVAS/WG=0) at 6 months (IRR 1.37 [95% CI 0.91 to 2.08], P=0.132). Addition of PLEX showed no benefit on remission-induction at 6 months (IRR 0.73 [95% CI 0.44 to 1.22], P=0.230), the rate of ESKD and/or death at 18 months (IRR 1.05 [95% CI 0.51 to 2.18], P=0.891), progression to ESKD (IRR 1.06 [95% CI 0.50 to 2.25], P=0.887), and survival at 24 months (IRR 0.54 [95% CI 0.16 to 1.85], P=0.330). CONCLUSIONS: The apparent benefits and risks of using CYC or RTX for the treatment of patients with AAV and severe kidney disease are balanced. The addition of PLEX to standard remission-induction therapy showed no benefit in our cohort. A randomized controlled trial is the only satisfactory means to evaluate efficacy of remission-induction treatments in AAV with severe renal involvement.",

author = "Moura, {Marta Casal} and Irazabal, {Maria V.} and Alfonso Eirin and Ladan Zand and Sanjeev Sethi and Borah, {Bijan J.} and Winters, {Jeffrey L.} and Moriarty, {James P.} and Rodrigo Cartin-Ceba and Alvise Berti and Misbah Baqir and Thompson, {Gwen E.} and Ashima Makol and Warrington, {Kenneth J.} and Viengneesee Thao and Ulrich Specks and Fervenza, {Fernando C.}",

note = "Funding Information: Dr. Marta Casal Moura, Dr. Ulrich Specks, and Dr. Fernando C. Fervenza designed the study. Dr. Marta Casal Moura, Dr. Maria V. Irazabal, and Dr. Alfonso Eirin abstracted the data. Dr. Marta Casal Moura, Dr. Sanjeev Sethi, Dr. Ulrich Specks, and Dr. Fernando C. Fervenza analyzed the data. Dr. Marta Casal Moura, Dr. Bijan J. Borah, Mr. James P. Moriarty, and Miss Viengneesee Thao performed the statistical analysis. Dr. Marta Casal Moura, Dr. Ladan Zand, Dr. Ulrich Specks, and Dr. Fernando C. Fervenza drafted and revised the paper. All authors provided input for the final version of the manuscript. Dr. Fernando C. Fervenza received unrestricted grants from Genentech Inc., South San Francisco, CA, outside the submitted work. Dr. Ulrich Specks reports grants from Genentech, grants from Bristol Myer Squibb, grants and personal fees from ChemoCentryx, grants from GSK, grants and other from AstraZeneca, and other from InsMed, outside the submitted work. Dr. Kenneth Warrington reports grants from Eli Lilly, grants from Roche/Genentech, grants from GlaxoSmithKline, grants from Kiniksa, personal fees from Roche/ Genentech, and personal fees from Sanofi, outside the submitted work. Funding Information: The study was supported by an internal grant from the Mayo Nephrology Collaborative Group, Mayo Foundation. Publisher Copyright: Copyright {\textcopyright} 2020 by the American Society of Nephrology",

year = "2020",

month = nov,

doi = "10.1681/ASN.2019111197",

language = "English (US)",

volume = "31",

pages = "2688--2704",

journal = "Journal of the American Society of Nephrology",

issn = "1046-6673",

publisher = "American Society of Nephrology",

number = "11",

}

TY - JOUR

T1 - Efficacy of rituximab and plasma exchange in antineutrophil cytoplasmic antibody-associated vasculitis with severe kidney disease

AU - Moura, Marta Casal

AU - Irazabal, Maria V.

AU - Eirin, Alfonso

AU - Zand, Ladan

AU - Sethi, Sanjeev

AU - Borah, Bijan J.

AU - Winters, Jeffrey L.

AU - Moriarty, James P.

AU - Cartin-Ceba, Rodrigo

AU - Berti, Alvise

AU - Baqir, Misbah

AU - Thompson, Gwen E.

AU - Makol, Ashima

AU - Warrington, Kenneth J.

AU - Thao, Viengneesee

AU - Specks, Ulrich

AU - Fervenza, Fernando C.

N1 - Funding Information: Dr. Marta Casal Moura, Dr. Ulrich Specks, and Dr. Fernando C. Fervenza designed the study. Dr. Marta Casal Moura, Dr. Maria V. Irazabal, and Dr. Alfonso Eirin abstracted the data. Dr. Marta Casal Moura, Dr. Sanjeev Sethi, Dr. Ulrich Specks, and Dr. Fernando C. Fervenza analyzed the data. Dr. Marta Casal Moura, Dr. Bijan J. Borah, Mr. James P. Moriarty, and Miss Viengneesee Thao performed the statistical analysis. Dr. Marta Casal Moura, Dr. Ladan Zand, Dr. Ulrich Specks, and Dr. Fernando C. Fervenza drafted and revised the paper. All authors provided input for the final version of the manuscript. Dr. Fernando C. Fervenza received unrestricted grants from Genentech Inc., South San Francisco, CA, outside the submitted work. Dr. Ulrich Specks reports grants from Genentech, grants from Bristol Myer Squibb, grants and personal fees from ChemoCentryx, grants from GSK, grants and other from AstraZeneca, and other from InsMed, outside the submitted work. Dr. Kenneth Warrington reports grants from Eli Lilly, grants from Roche/Genentech, grants from GlaxoSmithKline, grants from Kiniksa, personal fees from Roche/ Genentech, and personal fees from Sanofi, outside the submitted work. Funding Information: The study was supported by an internal grant from the Mayo Nephrology Collaborative Group, Mayo Foundation. Publisher Copyright: Copyright © 2020 by the American Society of Nephrology

PY - 2020/11

Y1 - 2020/11

N2 - BACKGROUND: Treatment of patients with ANCA-associated vasculitis (AAV) and severe renal involvement is not established. We describe outcomes in response to rituximab (RTX) versus cyclophosphamide (CYC) and plasma exchange (PLEX).METHODS: A retrospective cohort study of MPO- or PR3-ANCA-positive patients with AAV (MPA and GPA) and severe kidney disease (eGFR <30 ml/min per 1.73 m 2). Remission, relapse, ESKD and death after remission-induction with CYC or RTX, with or without the use of PLEX, were compared. RESULTS: Of 467 patients with active renal involvement, 251 had severe kidney disease. Patients received CYC ( n=161) or RTX ( n=64) for remission-induction, and 51 were also treated with PLEX. Predictors for ESKD and/or death at 18 months were eGFR <15 ml/min per 1.73 m 2 at diagnosis (IRR 3.09 [95% CI 1.49 to 6.40], P=0.002), renal recovery (IRR 0.27 [95% CI 0.12 to 0.64], P=0.003) and renal remission at 6 months (IRR 0.40 [95% CI 0.18 to 0.90], P=0.027). RTX was comparable to CYC in remission-induction (BVAS/WG=0) at 6 months (IRR 1.37 [95% CI 0.91 to 2.08], P=0.132). Addition of PLEX showed no benefit on remission-induction at 6 months (IRR 0.73 [95% CI 0.44 to 1.22], P=0.230), the rate of ESKD and/or death at 18 months (IRR 1.05 [95% CI 0.51 to 2.18], P=0.891), progression to ESKD (IRR 1.06 [95% CI 0.50 to 2.25], P=0.887), and survival at 24 months (IRR 0.54 [95% CI 0.16 to 1.85], P=0.330). CONCLUSIONS: The apparent benefits and risks of using CYC or RTX for the treatment of patients with AAV and severe kidney disease are balanced. The addition of PLEX to standard remission-induction therapy showed no benefit in our cohort. A randomized controlled trial is the only satisfactory means to evaluate efficacy of remission-induction treatments in AAV with severe renal involvement.

AB - BACKGROUND: Treatment of patients with ANCA-associated vasculitis (AAV) and severe renal involvement is not established. We describe outcomes in response to rituximab (RTX) versus cyclophosphamide (CYC) and plasma exchange (PLEX).METHODS: A retrospective cohort study of MPO- or PR3-ANCA-positive patients with AAV (MPA and GPA) and severe kidney disease (eGFR <30 ml/min per 1.73 m 2). Remission, relapse, ESKD and death after remission-induction with CYC or RTX, with or without the use of PLEX, were compared. RESULTS: Of 467 patients with active renal involvement, 251 had severe kidney disease. Patients received CYC ( n=161) or RTX ( n=64) for remission-induction, and 51 were also treated with PLEX. Predictors for ESKD and/or death at 18 months were eGFR <15 ml/min per 1.73 m 2 at diagnosis (IRR 3.09 [95% CI 1.49 to 6.40], P=0.002), renal recovery (IRR 0.27 [95% CI 0.12 to 0.64], P=0.003) and renal remission at 6 months (IRR 0.40 [95% CI 0.18 to 0.90], P=0.027). RTX was comparable to CYC in remission-induction (BVAS/WG=0) at 6 months (IRR 1.37 [95% CI 0.91 to 2.08], P=0.132). Addition of PLEX showed no benefit on remission-induction at 6 months (IRR 0.73 [95% CI 0.44 to 1.22], P=0.230), the rate of ESKD and/or death at 18 months (IRR 1.05 [95% CI 0.51 to 2.18], P=0.891), progression to ESKD (IRR 1.06 [95% CI 0.50 to 2.25], P=0.887), and survival at 24 months (IRR 0.54 [95% CI 0.16 to 1.85], P=0.330). CONCLUSIONS: The apparent benefits and risks of using CYC or RTX for the treatment of patients with AAV and severe kidney disease are balanced. The addition of PLEX to standard remission-induction therapy showed no benefit in our cohort. A randomized controlled trial is the only satisfactory means to evaluate efficacy of remission-induction treatments in AAV with severe renal involvement.

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JF - Journal of the American Society of Nephrology

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Efficacy of rituximab and plasma exchange in antineutrophil cytoplasmic antibody-associated vasculitis with severe kidney disease

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