Date: Sunday, November 5, 2017
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose: Lupus nephritis (LN) remains one of the most serious complications of SLE, occurring in up to 50% of patients. Current LN treatments are not sufficiently efficacious, are accompanied by significant off-target toxicities and result in a high percent of patients progressing to end stage renal disease. Thus, additional efforts are needed to understand LN at the molecular level, and to identify clinical responsiveness with specific molecular pathways.
Methods: SLE patients with proteinuria and suspected LN (n=105) were enrolled over 15 months by 12 US-based lupus centers to the RA/Lupus Accelerated Medicines Partnership Phase I program. Demographic, clinical, and therapeutic information was gathered using standard case report forms and entered into a study-specific database. ACR and SLICC SLE classification criteria, biopsy information, modified SELENA-SLEDAI, laboratory values and patient reported outcomes (PROMIS29) were collected. Serum, plasma, PBMCs, total blood leukocytes, urine, urine cells, and renal biopsy tissue were collected, with non-lesional, non-sun exposed skin biopsies in 25%. Complete renal response was considered improvement of urine protein to <500mg (or UPCR <0.5) and normal serum creatinine (or up to 125% of baseline) with prednisone taper, while partial response required improvement of urine protein by ≥50%.
Results: Of the 105 SLE patients recruited, 93 (89%) were female and most were non-Caucasian (n=84; 80%), including 28% Hispanic, 39% African-American, 11% Asian, 2% mixed ethnicity/not reported. Of the SLE renal biopsies (n=105), 75% were ISN Class III, IV, V or mixed. LN patients were on average 33.7 years of age (range: 14-58) with a baseline urine protein:creatinine ratio of 3.3 (with 34% > 3; n=21), 70% anti-dsDNA positive (n=48), 84% with low complement levels (n=59) and 39% with Hg < 10 g/dL (n=28). The average SLEDAI was 12.3, with 56% of this group presenting with global disease activity (e.g. 2 organ systems active in addition to renal, e.g. arthritis, skin, serositis). Analysis of 30 LN patients with longitudinal information revealed that 33% achieved complete response and 17% partial response to standard of care (SOC) therapy at 6 months. LN patients with extra renal disease activity were twice as likely to be renal non-responders to SOC (n=10 NR; n=5 CR/PR) than those LN patients whose disease activity was limited to renal and immunologic features only (n=6 NR; n=9 CR/PR).
Conclusion: These preliminary findings suggest that renal response to current SOC may occur more often in patients without other active manifestations of lupus. Significant clinical heterogeneity exists between LN patients emphasizing a need for deeper molecular phenotyping.
To cite this abstract in AMA style:James JA, Petri M, Putterman C, Diamond B, Wofsy D, Lee CH, Fine D, Broder AR, Clancy RM, Izmirly PM, Belmont M, Bornkamp N, Davidson A, Tosta P, Kalunian KC, Park M, Dall'Era M, Furie R, Massarotti E, Hernandez GT, Payan-Schober F, Connery SM, Kamen DL, Lee I, Pendergraft W III, Anolik JH, Shah U, Raychaudhuri S, Lee YC, Guthridge JM, Holers VM, Utz PJ, Pichavant M, Gupta R, Maecker HT, Weisman M, Buyon JP. Lupus Nephritis in Isolation or Accompanied By Extra-Renal Manifestations: Early Lessons from the Accelerating Medicines Partnership [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/lupus-nephritis-in-isolation-or-accompanied-by-extra-renal-manifestations-early-lessons-from-the-accelerating-medicines-partnership/. Accessed September 25, 2021.
« Back to 2017 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/lupus-nephritis-in-isolation-or-accompanied-by-extra-renal-manifestations-early-lessons-from-the-accelerating-medicines-partnership/