Longitudinal patterns and predictors of response to standard-of-care therapy in lupus nephritis: data from the Accelerating Medicines Partnership Lupus Network
Authors: Izmirly Peter M. , Kim Mimi Y. , Carlucci Philip M. , Preisinger Katherine , Cohen Brooke Z. , Deonaraine Kristina , Zaminski Devyn , Dall’Era Maria , Kalunian Kenneth , Fava Andrea , Belmont H. Michael , Wu Ming , Putterman Chaim , Anolik Jennifer , Barnas Jennifer L. , Diamond Betty , Davidson Anne , Wofsy David , Kamen Diane , James Judith A. , Guthridge Joel M. , Apruzzese William , Rao Deepak A. , Weisman Michael H. ,   The Accelerating Medicines Partnership in RA/SLE Network, Tabechian Darren , Thiele Ralf , Hossler Jennifer , Boyce Brendan , Meednu Nida , Rangel-Moreno Javier , Ritchlin Christopher , Bykerk Vivian , Donlin Laura , Goodman Susan , Ivashkiv Lionel , Pernis Alessandra , DiCarlo Ed , Orange Dana , Carrino John , Nwawka Oganna , Yoshimi Endo , Satija Rahul , Ivashkiv Lionel , Darnell Robert , Figgie Mark , McNamara Michael , Moreland Larry W. , McGeachy Mandy J. , Kolls Jay , Wise Aaron , Cordle Andrew , Gregersen Peter , Horowitz Diane , Filer Andrew D. , Turner Jason , Adams Holly , Pitzalis Costantino , Kelly Stephen , Hands Rebecca , Brenner Michael , Todd Derrick , Wei Kevin , Rao Deepak , Mizoguchi Fumitaka , Holers V. Michael , Deane Kevin D. , Seifert Jennifer A. , Banda Nirmal K. , Firestein Gary S. , Boyle David , Ben-Artzi Ami , Forbess Lindsy , Gravallese Ellen , Salomon-Escoto Karen , Perlman Harris , Mandelin Arthur , Bacalao Emily , Parks Deborah , Atkinson John , Bathon Joan , Matteson Eric , Bridges Louis , Hughes Laura B. , Fox David , Ike Robert , Lee Chun-Hao , Fine Derek , Monroy-Trujillo Manny , Anolik Jennifer , Shah Ummara , Weisman Michael , Ishimori Mariko , Buyon Jill P. , Clancy Robert M. , Izmirly Peter , Belmont Michael , Bornkamp Nicole , Der Evan , Goilav Beatrice , Jordan Nicole , Schwartz Daniel , Pullman James , Smilek Dawn , Tosta Patti , Kretzler Matthias , Berthier Celine C. , Woodle F. Steve , Hildeman Dave , Brenner Michael , Rao Deepak , Robinson William , Nolan Garry , Gonzales Veronica , Brenner Michael , Rao Deepak , Wei Kevin , Lederer Jim , Keegan Joshua , Chicoine Adam , Liu Yanyan , Watts Gerald , Hacohen Nir , Arazi Arnon , Lieb David , Eisenhaure Thomas , Tuschl Thomas , Utz P. J. , Rohani-Pichavant Mina , Gupta Rohit , Maecker Holden , Sargent Maria , Raychaudhuri Soumya , Lee Yvonne , Slowikowski Kamil , Fonseka Chamith , Zhang Fan , Guitierrez-Arcelus Maria , Buschman Justine , Chi Jennifer , Mao Su-Yau , Serrate-Sztein Susana , Wang Yan , Chen Quan , Peyman John , Goldmuntz Ellen , Dunn Patrick , Petri Michelle , Buyon Jill , Furie Richard 
Published: February 2024

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.