Longitudinal patterns and predictors of response to standard-of-care therapy in lupus nephritis: data from the Accelerating Medicines Partnership Lupus Network

Peter M. Izmirly; Mimi Y. Kim; Philip M. Carlucci; Katherine Preisinger; Brooke Z. Cohen; Kristina Deonaraine; Devyn Zaminski; Maria Dall’Era; Kenneth Kalunian; Andrea Fava; H. Michael Belmont; Ming Wu; Chaim Putterman; Jennifer Anolik; Jennifer L. Barnas; Betty Diamond; Anne Davidson; David Wofsy; Diane Kamen; Judith A. James; Joel M. Guthridge; William Apruzzese; Deepak A. Rao; Michael H. Weisman; Michelle Petri; Jill Buyon; Richard Furie

doi:10.1186/s13075-024-03275-z

Longitudinal patterns and predictors of response to standard-of-care therapy in lupus nephritis: data from the Accelerating Medicines Partnership Lupus Network

Peter M. Izmirly, Mimi Y. Kim, Philip M. Carlucci, Katherine Preisinger, Brooke Z. Cohen, Kristina Deonaraine, Devyn Zaminski, Maria Dall’Era, Kenneth Kalunian, Andrea Fava, H. Michael Belmont, Ming Wu, Chaim Putterman, Jennifer Anolik, Jennifer L. Barnas, Betty Diamond, Anne Davidson, David Wofsy, Diane Kamen, Judith A. JamesJoel M. Guthridge, William Apruzzese, Deepak A. Rao, Michael H. Weisman, Michelle Petri, Jill Buyon, Richard Furie

Bar-Ilan University - Azrieli Faculty of Medicine

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

5 Scopus citations

Abstract

Background: Leveraging the Accelerating Medicines Partnership (AMP) Lupus Nephritis (LN) dataset, we evaluated longitudinal patterns, rates, and predictors of response to standard-of-care therapy in patients with lupus nephritis. Methods: Patients from US academic medical centers with class III, IV, and/or V LN and a baseline urine protein/creatinine (UPCR) ratio ≥ 1.0 (n = 180) were eligible for this analysis. Complete response (CR) required the following: (1) UPCR < 0.5; (2) normal serum creatinine (≤ 1.3 mg/dL) or, if abnormal, ≤ 125% of baseline; and (3) prednisone ≤ 10 mg/day. Partial response (PR) required the following: (1) > 50% reduction in UPCR; (2) normal serum creatinine or, if abnormal, ≤ 125% of baseline; and (3) prednisone dose ≤ 15 mg/day. Results: Response rates to the standard of care at week 52 were CR = 22.2%; PR = 21.7%; non-responder (NR) = 41.7%, and not determined (ND) = 14.4%. Only 8/180 (4.4%) patients had a week 12 CR sustained through week 52. Eighteen (10%) patients attained a week 12 PR or CR and sustained their responses through week 52 and 47 (26.1%) patients achieved sustained PR or CR at weeks 26 and 52. Week 52 CR or PR attainment was associated with baseline UPCR > 3 (OR_adj = 3.71 [95%CI = 1.34–10.24]; p = 0.012), > 25% decrease in UPCR from baseline to week 12 (OR_adj = 2.61 [95%CI = 1.07–6.41]; p = 0.036), lower chronicity index (OR_{adj =} 1.33 per unit decrease [95%CI = 1.10–1.62]; p = 0.003), and positive anti-dsDNA antibody (OR_adj = 2.61 [95%CI = 0.93–7.33]; p = 0.069). Conclusions: CR and PR rates at week 52 were consistent with the standard-of-care response rates observed in prospective registrational LN trials. Low sustained response rates underscore the need for more efficacious therapies and highlight how critically important it is to understand the molecular pathways associated with response and non-response.

Original language	English
Article number	54
Journal	Arthritis Research and Therapy
Volume	26
Issue number	1
DOIs	https://doi.org/10.1186/s13075-024-03275-z
State	Published - 20 Feb 2024

Bibliographical note

Publisher Copyright:
© The Author(s) 2024.

Funding

The authors would like to thank Benjamin Wainwright for assistance in preparing this manuscript. Some data were previously presented in preliminary form as an abstract at the 2021 annual meeting of the American College of Rheumatology. The funding source had no role in the drafting of this manuscript or the analyses presented therein. The Accelerating Medicines Partnership in RA/SLE Network AMP RA Network Rochester Jennifer Anolik Darren Tabechian Ralf Thiele Jennifer Hossler Brendan Boyce Nida Meednu Javier Rangel-Moreno Christopher Ritchlin Hospital for Special Surgery (HSS) Vivian Bykerk Laura Donlin Susan Goodman Lionel Ivashkiv Alessandra Pernis Ed DiCarlo Dana Orange John Carrino Oganna (Kenny) Nwawka Endo Yoshimi Rahul Satija Lionel Ivashkiv Robert Darnell Mark Figgie Michael McNamara University of Pittsburgh Larry W. Moreland Mandy J. McGeachy Jay Kolls Aaron Wise Andrew Cordle Feinstein/Northwell Peter Gregersen Diane Horowitz UK Birmingham (under Feinstein/Northwell) Andrew D. Filer Jason Turner Holly Adams UK London (under Feinstein/Northwell) Costantino Pitzalis Stephen Kelly Rebecca Hands Brigham and Women’s Hospital Michael Brenner Derrick Todd Kevin Wei Deepak Rao Fumitaka Mizoguchi University of Colorado (EMORA) V. Michael Holers Kevin D. Deane Jennifer A. Seifert Nirmal K. Banda University of California San Diego (EMORA) Gary S. Firestein David Boyle Cedars Sinai (EMORA) Michael H. Weisman Ami Ben-Artzi Lindsy Forbess University of Massachusetts (EMORA) Ellen Gravallese Karen Salomon-Escoto Northwestern University (REASON under EMORA Network) Harris Perlman Arthur Mandelin Emily Bacalao Washington University (REASON) Deborah Parks John Atkinson Columbia University (REASON) Joan Bathon Mayo Clinic (REASON) Eric Matteson University of Alabama (REASON) Louis Bridges Laura B. Hughes Michigan (REASON) David Fox Robert Ike AMP SLE Network Johns Hopkins Michelle Petri Chun-Hao Lee Derek Fine Manny Monroy-Trujillo Rochester Jennifer Anolik Ummara Shah Cedars Michael Weisman Mariko Ishimori New York University (NYU) (METRO) Jill P. Buyon Robert M. Clancy Peter Izmirly Michael Belmont Amit Saxena Ming Wu Nicole Bornkamp Albert Einstein College of Medicine (METRO) Chaim Putterman Evan Der Beatrice Goilav Nicole Jordan Daniel Schwartz James Pullman University of California San Francisco (PEARL) David Wofsy Dawn Smilek Patti Tosta Feinstein/Northwell (PEARL) Betty Diamond Michigan (PEARL) Matthias Kretzler Celine C. Berthier University of Cincinnati (PEARL) F. Steve Woodle Dave Hildeman Brigham and Women’s Hospital (PEARL) Michael Brenner Deepak Rao Technology sites STAMP (Stanford) William Robinson Garry Nolan Veronica Gonzales Brigham and Women’s Hospital Michael Brenner Deepak Rao Kevin Wei Jim Lederer Joshua Keegan Adam Chicoine Yanyan Liu Gerald Watts Broad Institute Nir Hacohen Arnon Arazi David Lieb Thomas Eisenhaure Rockefeller (METRO) Thomas Tuschl AMP Operations Network William Apruzzese (NIAMS) Leadership Center (Stanford) PJ Utz Mina Rohani-Pichavant DCMG Rohit Gupta Holden Maecker TRG (at Oklahoma Medical Research Foundation) Judith A. James Joel M. Guthridge Wade DeJager Susan Macwana SBG Soumya Raychaudhuri Yvonne Lee Kamil Slowikowski Chamith Fonseka Fan Zhang Maria Guitierrez-Arcelus NIH/NIAMS Justine Buschman Jennifer Chi Su-Yau Mao Susana Serrate-Sztein Yan Wang NIH/NIAID Quan Chen John Peyman Ellen Goldmuntz ImmPort Patrick Dunn

Funders	Funder number
Andrew D. Filer Jason Turner Holly Adams UK London
Berthier University of Cincinnati
Deborah Parks John Atkinson Columbia University
EMORA
Eric Matteson University of Alabama
Joan Bathon Mayo Clinic
METRO
Michael H. Weisman Ami Ben-Artzi Lindsy Forbess University of Massachusetts
Michael Holers Kevin D. Deane Jennifer A. Seifert Nirmal K. Banda University of California San Diego
NIAID Quan Chen John Peyman Ellen Goldmuntz ImmPort Patrick Dunn
Nicole Bornkamp Albert Einstein College of Medicine
Nwawka Endo Yoshimi Rahul Satija Lionel Ivashkiv Robert Darnell Mark Figgie Michael McNamara University of Pittsburgh Larry W. Moreland Mandy J. McGeachy Jay Kolls Aaron Wise Andrew Cordle Feinstein/Northwell Peter Gregersen Diane Horowitz UK Birmingham
REASON
SLE Network Johns Hopkins Michelle Petri Chun-Hao Lee Derek Fine Manny Monroy-Trujillo Rochester Jennifer Anolik Ummara Shah Cedars Michael Weisman Mariko Ishimori New York University
Thomas Tuschl AMP Operations Network William Apruzzese
Yanyan Liu Gerald Watts Broad Institute Nir Hacohen Arnon Arazi David Lieb Thomas Eisenhaure Rockefeller
National Institutes of Health
National Institute of Arthritis and Musculoskeletal and Skin Diseases
New York University
Oklahoma Medical Research Foundation
Pearl Therapeutics

Keywords

Lupus nephritis
Outcome
Renal biopsy
Systemic lupus erythematosus (SLE)

Access to Document

10.1186/s13075-024-03275-z

Cite this

Izmirly, P. M., Kim, M. Y., Carlucci, P. M., Preisinger, K., Cohen, B. Z., Deonaraine, K., Zaminski, D., Dall’Era, M., Kalunian, K., Fava, A., Belmont, H. M., Wu, M., Putterman, C., Anolik, J., Barnas, J. L., Diamond, B., Davidson, A., Wofsy, D., Kamen, D., ... Furie, R. (2024). Longitudinal patterns and predictors of response to standard-of-care therapy in lupus nephritis: data from the Accelerating Medicines Partnership Lupus Network. Arthritis Research and Therapy, 26(1), Article 54. https://doi.org/10.1186/s13075-024-03275-z

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title = "Longitudinal patterns and predictors of response to standard-of-care therapy in lupus nephritis: data from the Accelerating Medicines Partnership Lupus Network",

abstract = "Background: Leveraging the Accelerating Medicines Partnership (AMP) Lupus Nephritis (LN) dataset, we evaluated longitudinal patterns, rates, and predictors of response to standard-of-care therapy in patients with lupus nephritis. Methods: Patients from US academic medical centers with class III, IV, and/or V LN and a baseline urine protein/creatinine (UPCR) ratio ≥ 1.0 (n = 180) were eligible for this analysis. Complete response (CR) required the following: (1) UPCR < 0.5; (2) normal serum creatinine (≤ 1.3 mg/dL) or, if abnormal, ≤ 125% of baseline; and (3) prednisone ≤ 10 mg/day. Partial response (PR) required the following: (1) > 50% reduction in UPCR; (2) normal serum creatinine or, if abnormal, ≤ 125% of baseline; and (3) prednisone dose ≤ 15 mg/day. Results: Response rates to the standard of care at week 52 were CR = 22.2%; PR = 21.7%; non-responder (NR) = 41.7%, and not determined (ND) = 14.4%. Only 8/180 (4.4%) patients had a week 12 CR sustained through week 52. Eighteen (10%) patients attained a week 12 PR or CR and sustained their responses through week 52 and 47 (26.1%) patients achieved sustained PR or CR at weeks 26 and 52. Week 52 CR or PR attainment was associated with baseline UPCR > 3 (ORadj = 3.71 [95%CI = 1.34–10.24]; p = 0.012), > 25% decrease in UPCR from baseline to week 12 (ORadj = 2.61 [95%CI = 1.07–6.41]; p = 0.036), lower chronicity index (ORadj = 1.33 per unit decrease [95%CI = 1.10–1.62]; p = 0.003), and positive anti-dsDNA antibody (ORadj = 2.61 [95%CI = 0.93–7.33]; p = 0.069). Conclusions: CR and PR rates at week 52 were consistent with the standard-of-care response rates observed in prospective registrational LN trials. Low sustained response rates underscore the need for more efficacious therapies and highlight how critically important it is to understand the molecular pathways associated with response and non-response.",

keywords = "Lupus nephritis, Outcome, Renal biopsy, Systemic lupus erythematosus (SLE)",

author = "Izmirly, {Peter M.} and Kim, {Mimi Y.} and Carlucci, {Philip M.} and Katherine Preisinger and Cohen, {Brooke Z.} and Kristina Deonaraine and Devyn Zaminski and Maria Dall{\textquoteright}Era and Kenneth Kalunian and Andrea Fava and Belmont, {H. Michael} and Ming Wu and Chaim Putterman and Jennifer Anolik and Barnas, {Jennifer L.} and Betty Diamond and Anne Davidson and David Wofsy and Diane Kamen and James, {Judith A.} and Guthridge, {Joel M.} and William Apruzzese and Rao, {Deepak A.} and Weisman, {Michael H.} and Michelle Petri and Jill Buyon and Richard Furie",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2024.",

year = "2024",

month = feb,

day = "20",

doi = "10.1186/s13075-024-03275-z",

language = "אנגלית",

volume = "26",

journal = "Arthritis Research and Therapy",

issn = "1478-6354",

publisher = "BioMed Central Ltd.",

number = "1",

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Izmirly, PM, Kim, MY, Carlucci, PM, Preisinger, K, Cohen, BZ, Deonaraine, K, Zaminski, D, Dall’Era, M, Kalunian, K, Fava, A, Belmont, HM, Wu, M, Putterman, C, Anolik, J, Barnas, JL, Diamond, B, Davidson, A, Wofsy, D, Kamen, D, James, JA, Guthridge, JM, Apruzzese, W, Rao, DA, Weisman, MH, Petri, M, Buyon, J & Furie, R 2024, 'Longitudinal patterns and predictors of response to standard-of-care therapy in lupus nephritis: data from the Accelerating Medicines Partnership Lupus Network', Arthritis Research and Therapy, vol. 26, no. 1, 54. https://doi.org/10.1186/s13075-024-03275-z

TY - JOUR

T1 - Longitudinal patterns and predictors of response to standard-of-care therapy in lupus nephritis

T2 - data from the Accelerating Medicines Partnership Lupus Network

AU - Izmirly, Peter M.

AU - Kim, Mimi Y.

AU - Carlucci, Philip M.

AU - Preisinger, Katherine

AU - Cohen, Brooke Z.

AU - Deonaraine, Kristina

AU - Zaminski, Devyn

AU - Dall’Era, Maria

AU - Kalunian, Kenneth

AU - Fava, Andrea

AU - Belmont, H. Michael

AU - Wu, Ming

AU - Putterman, Chaim

AU - Anolik, Jennifer

AU - Barnas, Jennifer L.

AU - Diamond, Betty

AU - Davidson, Anne

AU - Wofsy, David

AU - Kamen, Diane

AU - James, Judith A.

AU - Guthridge, Joel M.

AU - Apruzzese, William

AU - Rao, Deepak A.

AU - Weisman, Michael H.

AU - Petri, Michelle

AU - Buyon, Jill

AU - Furie, Richard

PY - 2024/2/20

Y1 - 2024/2/20

N2 - Background: Leveraging the Accelerating Medicines Partnership (AMP) Lupus Nephritis (LN) dataset, we evaluated longitudinal patterns, rates, and predictors of response to standard-of-care therapy in patients with lupus nephritis. Methods: Patients from US academic medical centers with class III, IV, and/or V LN and a baseline urine protein/creatinine (UPCR) ratio ≥ 1.0 (n = 180) were eligible for this analysis. Complete response (CR) required the following: (1) UPCR < 0.5; (2) normal serum creatinine (≤ 1.3 mg/dL) or, if abnormal, ≤ 125% of baseline; and (3) prednisone ≤ 10 mg/day. Partial response (PR) required the following: (1) > 50% reduction in UPCR; (2) normal serum creatinine or, if abnormal, ≤ 125% of baseline; and (3) prednisone dose ≤ 15 mg/day. Results: Response rates to the standard of care at week 52 were CR = 22.2%; PR = 21.7%; non-responder (NR) = 41.7%, and not determined (ND) = 14.4%. Only 8/180 (4.4%) patients had a week 12 CR sustained through week 52. Eighteen (10%) patients attained a week 12 PR or CR and sustained their responses through week 52 and 47 (26.1%) patients achieved sustained PR or CR at weeks 26 and 52. Week 52 CR or PR attainment was associated with baseline UPCR > 3 (ORadj = 3.71 [95%CI = 1.34–10.24]; p = 0.012), > 25% decrease in UPCR from baseline to week 12 (ORadj = 2.61 [95%CI = 1.07–6.41]; p = 0.036), lower chronicity index (ORadj = 1.33 per unit decrease [95%CI = 1.10–1.62]; p = 0.003), and positive anti-dsDNA antibody (ORadj = 2.61 [95%CI = 0.93–7.33]; p = 0.069). Conclusions: CR and PR rates at week 52 were consistent with the standard-of-care response rates observed in prospective registrational LN trials. Low sustained response rates underscore the need for more efficacious therapies and highlight how critically important it is to understand the molecular pathways associated with response and non-response.

AB - Background: Leveraging the Accelerating Medicines Partnership (AMP) Lupus Nephritis (LN) dataset, we evaluated longitudinal patterns, rates, and predictors of response to standard-of-care therapy in patients with lupus nephritis. Methods: Patients from US academic medical centers with class III, IV, and/or V LN and a baseline urine protein/creatinine (UPCR) ratio ≥ 1.0 (n = 180) were eligible for this analysis. Complete response (CR) required the following: (1) UPCR < 0.5; (2) normal serum creatinine (≤ 1.3 mg/dL) or, if abnormal, ≤ 125% of baseline; and (3) prednisone ≤ 10 mg/day. Partial response (PR) required the following: (1) > 50% reduction in UPCR; (2) normal serum creatinine or, if abnormal, ≤ 125% of baseline; and (3) prednisone dose ≤ 15 mg/day. Results: Response rates to the standard of care at week 52 were CR = 22.2%; PR = 21.7%; non-responder (NR) = 41.7%, and not determined (ND) = 14.4%. Only 8/180 (4.4%) patients had a week 12 CR sustained through week 52. Eighteen (10%) patients attained a week 12 PR or CR and sustained their responses through week 52 and 47 (26.1%) patients achieved sustained PR or CR at weeks 26 and 52. Week 52 CR or PR attainment was associated with baseline UPCR > 3 (ORadj = 3.71 [95%CI = 1.34–10.24]; p = 0.012), > 25% decrease in UPCR from baseline to week 12 (ORadj = 2.61 [95%CI = 1.07–6.41]; p = 0.036), lower chronicity index (ORadj = 1.33 per unit decrease [95%CI = 1.10–1.62]; p = 0.003), and positive anti-dsDNA antibody (ORadj = 2.61 [95%CI = 0.93–7.33]; p = 0.069). Conclusions: CR and PR rates at week 52 were consistent with the standard-of-care response rates observed in prospective registrational LN trials. Low sustained response rates underscore the need for more efficacious therapies and highlight how critically important it is to understand the molecular pathways associated with response and non-response.

KW - Lupus nephritis

KW - Outcome

KW - Renal biopsy

KW - Systemic lupus erythematosus (SLE)

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AN - SCOPUS:85185485075

SN - 1478-6354

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JO - Arthritis Research and Therapy

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Longitudinal patterns and predictors of response to standard-of-care therapy in lupus nephritis: data from the Accelerating Medicines Partnership Lupus Network

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Keywords

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