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. 2024 Feb 20;26(1):54.
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 #  1 , Mimi Y Kim #  2 , Philip M Carlucci  3 , Katherine Preisinger  3 , Brooke Z Cohen  3 , Kristina Deonaraine  3 , Devyn Zaminski  3 , Maria Dall'Era  4 , Kenneth Kalunian  5 , Andrea Fava  6 , H Michael Belmont  3 , Ming Wu  3 , Chaim Putterman  7 , Jennifer Anolik  8 , Jennifer L Barnas  8 , Betty Diamond  9 , Anne Davidson  9 , David Wofsy  4 , Diane Kamen  10 , Judith A James  11 , Joel M Guthridge  11 , William Apruzzese  12 , Deepak A Rao  13 , Michael H Weisman  14 ; Accelerating Medicines Partnership in RA/SLE Network; Michelle Petri  6 , Jill Buyon #  3 , Richard Furie #  9
Collaborators, Affiliations

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 et al. Arthritis Res Ther. .

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).

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Conflict of interest statement

The authors would like to disclose the following financial relationships: Izmirly, Peter Consultant: GSK, Momenta/Janssen; Kim, Mimi: None; Carlucci, Philip: none; Preisinger, Katherine: none; Zaminski, Devyn: none; Dall’Era, Maria: Consultant: GSK, Aurinia, AstraZeneca, Lilly, Biogen; Data Monitoring Committee: Janssen, Pfizer, Amgen; Kalunian, Kenneth: Advisor: AstraZeneca, RemeGen, BMS, Amgen, EquilliumBio, KezarBio, Aurinia, GSK, Roche/Genentech, Novarits, Horizon, Idorsia, Artivabio, Cabaletta, Merck, Alpine Immune Sciences, AbbVie, Vera Therapeutics, Aclaris Therapeutics, Gilead, Pfizer; Grants: Amgen, UCB, Acceleron, PreventionBio, Feinstein Institute, Alexion, NIH/MUSC, NIH/Immune Tolerance Network, Cugene, Kyowa Kirin, Daichi Sankyo; Fava, Andrea: none; Belmont, Michael: none; Wu, Ming: none; Putterman, Chaim: none; Anolik, Jennifer: Pending; Barnas, Jennifer: none; Diamond, Betty: Consultant: Nextcure, DBV, Alpine, iCell, Bayer, Magnolia, Kyverna, Nighthawk; Davidson, Anne: none; Wofsy, David: none; Kamen, Diane: Data safety and monitoring committee member: Alpine Immune Sciences; Data And Safety Monitoring Chair: Equillium; James, Judith: Advisor: GSK, Novartis; IP licensing and grant support: Progentec Biosciences; Guthridge, Joel: none; Apruzzese, William: Employment: Pfizer (began after this work concluded); Rao, Deepak: Consultant: GSK, AstraZeneca, Bristol-Myers Squibb, Pfizer; grant support unrelated to this work: Janssen, Bristol-Myers Squibb, Merck; Weisman, Michael: none; Petri, Michelle Consultant: Alexion, Amgen, AnaptysBio, Annexon Bio, Argenx, AstraZeneca, Axdev, Biogen, Boxer Capital, Cabaletto Bio, Caribou Biosciences Inc, CVS Health, Exo Therapeutics, Gilead Biosciences, GSK, Horizon Therapeutics, Idorsia Pharmaceuticals, Janssen, Kira Pharmaceuticals, Eli Lilly, MedShr, Momenta Pharmaceuticals, Nexstone Immunology, Nimbus Lakshmi, Proviant, Sanofi, Sinomab Biosciences, UCB; Invited speaker: Arthros-FocusMedEd, Aurinia; Data safety and monitoring board member: Emergent Biosolutions, IQVIA, Merck EMD Serono; grant support: Eli Lilly, Exagen, AstraZeneca, GSK, Thermofisher, Janssen, Aurinia; Buyon, Jill, Consultant: Bristol-Myers Squibb; GlaxoSmith Kline, Related Sciences, Ventus Therapeutics; Furie, Richard: Consultant: GSK, Genetech, Aurinia, Kezar.

Figures

Fig. 1
Fig. 1
Flow diagram of study enrollment
Fig. 2
Fig. 2
Response rates and graphical heat map displays of responses at each visit
See this image and copyright information in PMC

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