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Record W4391967782 · 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

2024· article· en· W4391967782 on OpenAlexfundno aff
Peter Izmirly, Mimi Kim, Philip M. Carlucci, Katherine Preisinger, Brooke Cohen, Kristina Deonaraine, Devyn Zaminski, Maria Dall’Era, Kenneth Kalunian, Andrea Fava, H. Michael Belmont, Ming Wu, Chaim Putterman, Jennifer H. Anolik, Jennifer L. Barnas, Betty Diamond, Anne Davidson, David Wofsy, Diane L. Kamen, Judith A. James, Joel M. Guthridge, William Apruzzese, Deepak A. Rao, Michael H. Weisman, Darren Tabechian, Ralf Thiele, Jennifer Hossler, Brendan F. Boyce, Nida Meednu, Javier Rangel‐Moreno, Christopher T. Ritchlin, Vivian P. Bykerk, Laura T. Donlin, Susan M. Goodman, Lionel B. Ivashkiv, Alessandra B. Pernis, Ed DiCarlo, Dana E. Orange, John A. Carrino, O. Nwawka, Endo Yoshimi, Rahul Satija, Robert B. Darnell, Mark P. Figgie, Michael McNamara, Larry W. Moreland, Mandy J. McGeachy, Jay Kolls, Aaron Wise, Andrew Cordle, Peter K. Gregersen, Diane Horowitz, Andrew Filer, Jason D. Turner, H. Adams, Costantino Pitzalis, Stephen Kelly, Rebecca Hands, Derrick J. Todd, Kevin Wei, Fumitaka Mizoguchi, V. Michael Holers, Kevin D. Deane, Jennifer Seifert, Nirmal K. Banda, Gary S. Firestein, David Boyle, Ami Ben‐Artzi, Lindsy Forbess, Ellen M. Gravallese, Karen Salomon-Escoto, Harris Perlman, Arthur M. Mandelin, Emily Bacalao, Deborah Parks, John Atkinson, Joan M. Bathon, Eric L. Matteson, Louis Bridges, Laura B. Hughes, David A. Fox, Robert W. Ike, Chun-Hao Lee, Derek M. Fine, Manny Monroy-Trujillo, Ummara Shah, Mariko Ishimori, Jill P. Buyon, Robert M. Clancy, Nicole Bornkamp, Evan Der, Béatrice Goilav, Nicole Jordan, Daniel Schwartz, James Pullman, Dawn E. Smilek, Patti Tosta, Matthias Kretzler, Céline C. Berthier, F. Steve Woodle, Dave Hildeman, Michael B. Brenner, William H. Robinson, Garry P. Nolan, Veronica Gonzales, Jim Lederer, Joshua Keegan, Adam Chicoine, Yanyan Liu, Gerald F. Watts, Nir Hacohen, Arnon Arazi, David Lieb, Thomas Eisenhaure, Thomas Tuschl, Paul J. Utz, Mina Rohani‐Pichavant, Rohit Gupta, Holden T. Maecker, Maria Sargent, Soumya Raychaudhuri, Yvonne Lee, Kamil Slowikowski, Chamith Y. Fonseka, Fan Zhang, Maria Guitierrez-Arcelus, Justine Buschman, Jennifer Chi, Su-Yau Mao, Susana Serrate-Sztein, Yan Wang, Quan Chen, John Peyman, Ellen Goldmuntz, Patrick Dunn, Michelle Petri, Richard Furie

Bibliographic record

VenueArthritis Research & Therapy · 2024
Typearticle
Languageen
FieldMedicine
TopicSystemic Lupus Erythematosus Research
Canadian institutionsnot available
FundersNational Institute of Arthritis and Musculoskeletal and Skin DiseasesUniversity of California, San DiegoYork UniversityNorthwestern UniversityOklahoma Medical Research FoundationUniversity of CincinnatiNational Institute of Allergy and Infectious DiseasesJohns Hopkins UniversityNational Institutes of HealthNorthwell Health
KeywordsMedicineLupus nephritisCreatininePrednisoneInternal medicineRheumatologyProteinuriaUrologySystemic lupus erythematosusGastroenterologyKidneyDisease

Abstract

fetched live from OpenAlex

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.008
metaresearch head score (Gemma)0.002
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.272
Threshold uncertainty score0.872

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0080.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.001
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0010.001
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.131
GPT teacher head0.403
Teacher spread0.271 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations25
Published2024
Admission routes1
Has abstractyes

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