Longitudinal patterns and predictors of response to standard-of-care therapy in lupus nephritis: data from the Accelerating Medicines Partnership Lupus Network
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, The Accelerating Medicines Partnership in RA/SLE Network, 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, Lionel B. Ivashkiv, 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, Michael Brenner, Derrick J. Todd, Kevin Wei, Deepak Rao, 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, Jennifer H. Anolik, Ummara Shah, Michael H. Weisman, Mariko Ishimori, Jill P. Buyon, Robert M. Clancy, Peter Izmirly, H. Michael Belmont, Nicole Bornkamp, Evan Der, Béatrice Goilav
Abstract
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.