Longitudinal patterns and predictors of response to standard-of-care therapy in lupus nephritis: data from the Accelerating Medicines Partnership Lupus Network
Arthritis Research & Therapy, 2024
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, The Accelerating Medicines Partnership in RA/SLE Network, Darren Tabechian, Ralf Thiele, Jennifer Hossler, Brendan Boyce, Nida Meednu, Javier Rangel-Moreno, Christopher Ritchlin, Vivian Bykerk, Laura Donlin, Susan Goodman, Lionel Ivashkiv, Alessandra Pernis, Ed DiCarlo, Dana Orange, John Carrino, Oganna Nwawka, Endo Yoshimi, Rahul Satija, Lionel Ivashkiv, Robert Darnell, Mark Figgie, Michael McNamara, Larry W. Moreland, Mandy J. McGeachy, Jay Kolls, Aaron Wise, Andrew Cordle, Peter Gregersen, Diane Horowitz, Andrew D. Filer, Jason Turner, Holly Adams, Costantino Pitzalis, Stephen Kelly, Rebecca Hands, Michael Brenner, Derrick Todd, Kevin Wei, Deepak Rao, Fumitaka Mizoguchi, V. Michael Holers, Kevin D. Deane, Jennifer A. Seifert, Nirmal K. Banda, Gary S. Firestein, David Boyle, Ami Ben-Artzi, Lindsy Forbess, Ellen Gravallese, Karen Salomon-Escoto, Harris Perlman, Arthur Mandelin, Emily Bacalao, Deborah Parks, John Atkinson, Joan Bathon, Eric Matteson, Louis Bridges, Laura B. Hughes, David Fox, Robert Ike, Chun-Hao Lee, Derek Fine, Manny Monroy-Trujillo, Jennifer Anolik, Ummara Shah, Michael Weisman, Mariko Ishimori, Jill P. Buyon, Robert M. Clancy, Peter Izmirly, Michael Belmont, Nicole Bornkamp, Evan Der, Beatrice Goilav, Nicole Jordan, Daniel Schwartz, James Pullman, Dawn Smilek, Patti Tosta, Matthias Kretzler, Celine C. Berthier, F. Steve Woodle, Dave Hildeman, Michael Brenner, Deepak Rao, William Robinson, Garry Nolan, Veronica Gonzales, Michael Brenner, Deepak Rao, Kevin Wei, Jim Lederer, Joshua Keegan, Adam Chicoine, Yanyan Liu, Gerald Watts, Nir Hacohen, Arnon Arazi, David Lieb, Thomas Eisenhaure, Thomas Tuschl, P. J. Utz, Mina Rohani-Pichavant, Rohit Gupta, Holden Maecker, Maria Sargent, Soumya Raychaudhuri, Yvonne Lee, Kamil Slowikowski, Chamith 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, Jill Buyon, Richard Furie
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.