ACR Meeting Abstracts

ACR Meeting Abstracts

  • Meetings
    • ACR Convergence 2024
    • ACR Convergence 2023
    • 2023 ACR/ARP PRSYM
    • ACR Convergence 2022
    • ACR Convergence 2021
    • ACR Convergence 2020
    • 2020 ACR/ARP PRSYM
    • 2019 ACR/ARP Annual Meeting
    • 2018-2009 Meetings
    • Download Abstracts
  • Keyword Index
  • Advanced Search
  • Your Favorites
    • Favorites
    • Login
    • View and print all favorites
    • Clear all your favorites
  • ACR Meetings

Abstract Number: 1002

Investigation of Pharmacodynamic Biomarkers in a Phase 2b Study in Patients with Moderate to Severe SLE Treated with the S1P1 Receptor Modulator Cenerimod

Daniel Strasser1, clélia Cahuzac2, peter Cornelisse2, Ouali Berkani2, Peter Groenen2 and Mark Murphy2, 1Idorsia Pharmaceuticals Ltd., Allschwil, Switzerland, 2Idorsia Pharmaceuticals Ltd, Allschwil, Switzerland

Meeting: ACR Convergence 2022

Keywords: Biomarkers, clinical trial, Systemic lupus erythematosus (SLE)

  • Tweet
  • Email
  • Print
Session Information

Date: Sunday, November 13, 2022

Title: SLE – Treatment Poster II

Session Type: Poster Session B

Session Time: 9:00AM-10:30AM

Background/Purpose: Sphingosine-1-phosphate (S1P) regulates lymphocyte egress from lymphoid organs into circulation. In a SLE proof-of-concept study, cenerimod—a potent, selective S1P1 receptor modulator—reduced circulating antibody-secreting cells and plasma IFN-associated biomarkers vs placebo (Strasser et al. rmdopen-2020-001261). Here, exploratory biomarkers associated with inflammation were evaluated in the phase 2b study (CARE) of cenerimod in moderate to severe SLE (NCT03742037).

Methods: Peripheral blood samples from patients with SLE participating in the phase 2b study (CARE) were collected at baseline and after 6 months of treatment with the S1P1 receptor modulator cenerimod. Samples were collected in PAXgene tubes for gene expression analysis and EDTA plasma tubes for plasma protein expression. Gene expression was analyzed using the modular immune profile test (MIP) from DxTerity®. A high IFN-1 gene expression signature status (IFN-1 high) was identified using a 4-gene expression signature (IFIT1, HERC5, IFI27, RSAD2). Plasma proteins were measured using fit-for-purpose validated antibody-based assays.

Results: At baseline, patients with SLE were identified as either IFN-1 high or IFN-1 low. The distribution was well balanced in the placebo (n=86) and cenerimod 4 mg group (n=85) with approximately 50% IFN-1 high in both treatment arms. At baseline, the IFN-1 gene expression signature (GES) showed a bimodal distribution, and correlated with the IFN beta, IFN gamma, plasmablasts, and inflammation GES. The IFN-1 GES did not correlate with other adaptive and innate immune cell GES. None of the GES correlated with the mSLEDAI-2K at baseline. At 6 months, cenerimod treatment modulated GES and proteins linked to several of those molecular pathways associated with SLE pathogenesis.

Conclusion: At baseline, patients with SLE presented systemic molecular heterogeneity with clear separation of patients into IFN-1 high and IFN-1 low phenotypes. Of note, the IFN-1 phenotypes correlated with other inflammatory pathways, revealing a complex inflammatory pathogenesis in SLE. Cenerimod showed the potential to modify several of these inflammatory pathways demonstrating its broad immune-modulatory pharmacodynamics.


Disclosures: D. Strasser, Idorsia Pharmaceuticals Ltd; c. Cahuzac, Idorsia Pharmaceuticals Ltd; p. Cornelisse, Idorsia Pharmaceuticals Ltd; O. Berkani, Idorsia Pharmaceuticals Ltd; P. Groenen, Idorsia Pharmaceuticals Ltd; M. Murphy, Idorsia Pharmaceuticals Ltd.

To cite this abstract in AMA style:

Strasser D, Cahuzac c, Cornelisse p, Berkani O, Groenen P, Murphy M. Investigation of Pharmacodynamic Biomarkers in a Phase 2b Study in Patients with Moderate to Severe SLE Treated with the S1P1 Receptor Modulator Cenerimod [abstract]. Arthritis Rheumatol. 2022; 74 (suppl 9). https://acrabstracts.org/abstract/investigation-of-pharmacodynamic-biomarkers-in-a-phase-2b-study-in-patients-with-moderate-to-severe-sle-treated-with-the-s1p1-receptor-modulator-cenerimod/. Accessed .
  • Tweet
  • Email
  • Print

« Back to ACR Convergence 2022

ACR Meeting Abstracts - https://acrabstracts.org/abstract/investigation-of-pharmacodynamic-biomarkers-in-a-phase-2b-study-in-patients-with-moderate-to-severe-sle-treated-with-the-s1p1-receptor-modulator-cenerimod/

Advanced Search

Your Favorites

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

All abstracts accepted to ACR Convergence are under media embargo once the ACR has notified presenters of their abstract’s acceptance. They may be presented at other meetings or published as manuscripts after this time but should not be discussed in non-scholarly venues or outlets. The following embargo policies are strictly enforced by the ACR.

Accepted abstracts are made available to the public online in advance of the meeting and are published in a special online supplement of our scientific journal, Arthritis & Rheumatology. Information contained in those abstracts may not be released until the abstracts appear online. In an exception to the media embargo, academic institutions, private organizations, and companies with products whose value may be influenced by information contained in an abstract may issue a press release to coincide with the availability of an ACR abstract on the ACR website. However, the ACR continues to require that information that goes beyond that contained in the abstract (e.g., discussion of the abstract done as part of editorial news coverage) is under media embargo until 10:00 AM ET on November 14, 2024. Journalists with access to embargoed information cannot release articles or editorial news coverage before this time. Editorial news coverage is considered original articles/videos developed by employed journalists to report facts, commentary, and subject matter expert quotes in a narrative form using a variety of sources (e.g., research, announcements, press releases, events, etc.).

Violation of this policy may result in the abstract being withdrawn from the meeting and other measures deemed appropriate. Authors are responsible for notifying colleagues, institutions, communications firms, and all other stakeholders related to the development or promotion of the abstract about this policy. If you have questions about the ACR abstract embargo policy, please contact ACR abstracts staff at [email protected].

Wiley

  • Online Journal
  • Privacy Policy
  • Permissions Policies
  • Cookie Preferences

© Copyright 2025 American College of Rheumatology