ACR Meeting Abstracts

ACR Meeting Abstracts

  • Home
  • Meetings Archive
    • ACR Convergence 2020
    • 2020 ACR/ARP PRSYM
    • 2019 ACR/ARP Annual Meeting
    • 2018 ACR/ARHP Annual Meeting
    • 2017 ACR/ARHP Annual Meeting
    • 2017 ACR/ARHP PRSYM
    • 2016-2009 Meetings
    • Download Abstracts
  • Keyword Index
  • Advanced Search
  • Your Favorites
    • Favorites
    • Login
    • Register
    • View and print all favorites
    • Clear all your favorites
  • Meeting Resource Center

Abstract Number: 2566

Nilotinib Treatment Effect In The Skin As Measured By DNA Microarray In Patients With Diffuse Systemic Sclerosis

Jessica K. Gordon1, Tammara A. Wood2, Robert F. Spiera1 and Michael L. Whitfield2, 1Rheumatology, Hospital for Special Surgery, New York, NY, 2Department of Genetics, Geisel School of Medicine at Dartmouth, Hanover, NH

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: Biomarkers, Gene Expression, Systemic sclerosis, treatment and tyrosine kinase inhibition

  • Tweet
  • Email
  • Print
Save to PDF
Session Information

Session Title: Systemic Sclerosis, Fibrosing Syndromes, and Raynaud's II

Session Type: Abstract Submissions (ACR)

Background/Purpose:

Gene expression profiling by DNA microarray is used to identify potential biomarkers in Systemic Sclerosis (SSc).  Discrete gene expression signatures have been observed to subset patients and correlate with clinical parameters.  We tested the hypothesis that treatment modulates gene expression in SSc skin in the context of an open label study of nilotinib to treat early diffuse cutaneous (dc)SSc. 

Methods:

Ten adult patients with early progressive dcSSc of <3 yrs since the initial SSc symptom were treated with nilotinib 400 mg PO twice daily.  Three mm punch biopsies of lesional forearm skin were performed at baseline and after 6 and 12 mos of treatment, and the Modified Rodnan Skin Score (MRSS) was recorded.  Clinical improvement was defined as improvement in MRSS by 20% from baseline.  Using this criterion, we classified 4 patients as improvers and 4 patients as non-improvers.  RNA was extracted from the whole skin, converted to cRNA, and hybridized to Agilent 8x60K whole human genome microarrays.  Significance Analysis of Microarrays (SAM) was used to identify genes differentially expressed between pre- and post-treatment skin biopsies for both improvers and non-improvers separately and together. Patients before and after 6 and 12 months of treatment were assigned to intrinsic subsets using a gene expression classifier algorithm. 

Results:

Eight out of 10 patients from the nilotinib trial had at least baseline and 6 month biopsies that were included in the gene expression analysis.  Patient characteristics (n=8) were: 75% female; median age 48.5 (IQR 41,53); median disease duration from the first non-Raynaud’s symptom of SSc: 0.67 (IQR 0.42, 0.71); baseline Modified Rodnan Skin Score (MRSS): 27.5 (IQR 22, 32); 62.5% RNA Pol3 positive; 25% Scl70 positive.  SAM identified 185 genes with significantly decreased expression post treatment in improvers.  These genes were significantly enriched for inflammatory response, hematopoiesis and cell-cell adhesion. In contrast, we did not find significant changes in gene expression post-treatment in non-improvers. Analysis of patient intrinsic subsets showed that 3 out of 4 non-improvers showed stable or increasing inflammatory signatures.  Improvers showed either rapid decrease in the inflammatory signature or absence of the inflammatory signature with concomitant stable or increasing fibroproliferative signatures. 

Conclusion:

We observed modulation of gene expression in skin as measured by DNA microarray in improvers but not in non-improvers during the course of the nilotinib trial.  Patients that did not show improvement had an inflammatory signature that was stable or increasing, whereas patients that improved show decreasing inflammatory and increasing fibroproliferative gene signatures. Whether these changes in gene-expression signify biological effect of nilotinib or natural history of scleroderma will require an untreated control group to determine.


Disclosure:

J. K. Gordon,
None;

T. A. Wood,
None;

R. F. Spiera,

Roche Pharmaceuticals,

2,

Novartis Pharmaceutical Corporation,

2,

GlaxoSmithKline,

2;

M. L. Whitfield,
None.

  • Tweet
  • Email
  • Print
Save to PDF

« Back to 2013 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/nilotinib-treatment-effect-in-the-skin-as-measured-by-dna-microarray-in-patients-with-diffuse-systemic-sclerosis/

Advanced Search

Your Favorites

You can save and print a list of your favorite abstracts by clicking the “Favorite” button at the bottom of any abstract. View your favorites »

ACR Convergence: Where Rheumatology Meets. All Virtual. November 5-9.

ACR Pediatric Rheumatology Symposium 2020

© COPYRIGHT 2021 AMERICAN COLLEGE OF RHEUMATOLOGY

Wiley

  • Home
  • Meetings Archive
  • Advanced Search
  • Meeting Resource Center
  • Online Journal
  • Privacy Policy
  • Permissions Policies
loading Cancel
Post was not sent - check your email addresses!
Email check failed, please try again
Sorry, your blog cannot share posts by email.
This site uses cookies: Find out more.