Lupus Nephritis in Isolation or Accompanied By Extra-Renal Manifestations: Early Lessons from the Accelerating Medicines Partnership

Judith A. James¹, Michelle Petri², Chaim Putterman³, Betty Diamond⁴, David Wofsy⁵, Chun Hao Lee⁶, Derek Fine⁶, Anna R. Broder⁷, Robert M. Clancy⁸, Peter M. Izmirly⁹, Michael Belmont¹⁰, Nicole Bornkamp¹¹, Anne Davidson¹², Patti Tosta¹³, Kenneth C. Kalunian¹⁴, Meyeon Park¹⁵, Maria Dall'Era¹⁶, Richard Furie¹⁷, Elena Massarotti¹⁸, German T. Hernandez¹⁹, Fernanda Payan-Schober²⁰, Sean M. Connery¹⁹, Diane L. Kamen²¹, Iris Lee²², William Pendergraft III²³, Jennifer H. Anolik²⁴, Ummara Shah²⁵, Soumya Raychaudhuri²⁶, Yvonne C. Lee²⁷, Joel M. Guthridge²⁸, V. Michael Holers²⁹, Paul J. Utz³⁰, Mina Pichavant³¹, Rohit Gupta³¹, Holden T. Maecker³², Michael Weisman³³ and Jill P. Buyon³⁴, ¹Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, ²Medicine (Rheumatology), Division of Rheumatology, Johns Hopkins University School of Medicine, MD, USA, Baltimore, MD, ³Division of Rheumatology, Albert Einstein College of Medicine, Bronx, NY, USA, Bronx, NY, ⁴Autoimmune and Musculoskeletal Diseases, The Feinstein Institute for Medical Research, Manhasset, NY, ⁵Rheumatology, UCSF, San Francisco, CA, ⁶Johns Hopkins University, Baltimore, MD, ⁷Albert Einstein College of Medicine, Bronx, NY, ⁸NYU School of Medicine, New York, NY, ⁹New York University School of Medicine, New York, NY, ¹⁰New York University, NYC, NY, ¹¹Medicine, New York University School of Medicine, New York, NY, ¹²Autoimmunity and Musculoskeletal Diseases, Feinstein Institute for Medical Research, Manhasset, NY, ¹³Immune Tolerance Network, San Francisco, CA, ¹⁴Division of Rheumatology, Allergy & Immunology, UCSD School of Medicine Center for Innovative Therapy, La Jolla, CA, ¹⁵University of California San Francisco, San Francisco, CA, ¹⁶Medicine/Rheumatology, University of California, San Francisco, San Francisco, CA, ¹⁷Hofstra Northwell, Manhasset, NY, ¹⁸Brigham and Women's Hospital, Boston, MA, ¹⁹Texas Tech University HSC El Paso, El Paso, TX, ²⁰Texas Tech University HSC El Paso, El Paso, TX, ²¹Medicine/Rheumatology & Immunology, Medical University of South Carolina, Charleston, SC, ²²Temple University Hospital, Philadelphia, PA, ²³Kidney Center, University of North Carolina, Chapel Hill, NC, ²⁴Medicine- Allergy, Immunology and Rheumatology, University of Rochester Medical Center, Rochester, NY, ²⁵Division of Rheumatology, New York University School of Medicine, NYC, NY, ²⁶Divisions of Genetics and Rheumatology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, ²⁷Rheumatology Immunology & Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, ²⁸Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, OKC, OK, ²⁹Rheumatology Division, University of Colorado School of Medicine, Aurora, CO, ³⁰Medicine, Stanford University School of Medicine, Stanford, CA, ³¹Stanford University, Stanford, CA, ³²Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA, ³³Cedars-Sinai Medical Center Division of Rheumatology, Los Angeles, CA, ³⁴Rheumatology, New York University School of Medicine, New York, NY

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: Nephritis and treatment

Session Information

Date: Sunday, November 5, 2017

Title: Systemic Lupus Erythematosus – Clinical Aspects and Treatment Poster I: Biomarkers and Outcomes

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.

Disclosure: J. A. James, None; M. Petri, Anthera Inc, 5,GlaxoSmithKline, 5,EMD Serono, 5,Eli Lilly and Company, 5,Bristol Meyer Squibb, 5,Amgen, 5,United Rheumatology, 5,Global Academy, 5,Exagen, 2; C. Putterman, None; B. Diamond, None; D. Wofsy, None; C. H. Lee, None; D. Fine, None; A. R. Broder, None; R. M. Clancy, None; P. M. Izmirly, None; M. Belmont, None; N. Bornkamp, None; A. Davidson, None; P. Tosta, None; K. C. Kalunian, Pfizer Inc, Gilead, UCB, Amgen, 2; M. Park, None; M. Dall'Era, None; R. Furie, None; E. Massarotti, Exagen, 5,BMS, 2,Springer Publishing, 7; G. T. Hernandez, None; F. Payan-Schober, None; S. M. Connery, None; D. L. Kamen, None; I. Lee, None; W. Pendergraft III, None; J. H. Anolik, None; U. Shah, None; S. Raychaudhuri, Pfizer Inc, 2,Roche Pharmaceuticals, 2; Y. C. Lee, Express Scripts, 1,Pfizer Inc, 2; J. M. Guthridge, None; V. M. Holers, None; P. J. Utz, None; M. Pichavant, None; R. Gupta, None; H. T. Maecker, None; M. Weisman, None; J. P. Buyon, None.

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 .

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