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: 1237

Treatment with OLT1177™, an Oral NLRP3 Inflammasome Inhibitor, Reduces Systemic Inflammation During Gout Flares in Humans

Viola Kluck1, Tim Jansen 2, Matthijs Janssen 3, Isak Tengensdal 4, Kiki Schraa 5, Maartje Cleophas 5, Damaris Skouras 6, Carlo Marchetti 4, Charles Dinarello 7 and Leo Joosten 8, 1Radboudumc, Nijmegen, Netherlands, 2Viecuri MC, Venlo, Netherlands, 3VieCuri Medical Center, Venlo, Netherlands, 4University of Colorado Denver, Denver, CO, 5Radboudumc, Nijmegen, 6Olatec Therapeutics LLC, New York, NY, 7University of Colorado Denver, Aurora, CO, 8Department of Internal Medicine and Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University Medical Center, Nijmegen, Netherlands

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: gout flares, NLRP3 inflammasome and New Therapeutics

  • Tweet
  • Email
  • Print
Session Information

Date: Monday, November 11, 2019

Title: Metabolic & Crystal Arthropathies Poster II: Clinical Trials & Basic Science

Session Type: Poster Session (Monday)

Session Time: 9:00AM-11:00AM

Background/Purpose: Gout flares are characteristically mediated by the pro-inflammatory cytokine interleukin (IL)-1β. Uptake of monosodium urate (MSU) crystals by macrophages activates the nucleotide-binding domain and leucine-rich repeat containing family, pyrin domain containing 3 (NLRP3) inflammasome, which converts intracellular pro-interleukin-1β (pro-IL-1β) to mature bioactive IL-1β by proteolytic cleavage. In the presence of concomitant pro-inflammatory stimuli, i.e., Toll-Like Receptor (TLR) agonists, transcription of IL-1β gene is induced and pro-IL-1β is rapidly converted into its active form. IL-1β binds to its receptor (IL-1R1) and induces a cascade of secondary inflammatory mediators including prostaglandins, cytokines and chemokines, resulting in a fulminant joint inflammation. Recently, OLT1177™, a β-sulfonyl nitrile compound, safe in humans, was shown to inhibit the NLRP3 inflammasome and inhibit joint inflammation in murine models of acute arthritis. This study explores the mechanisms by which oral OLT1177™ inhibits joint inflammation in humans with gout flares.

Methods: 29 patients with a gout flare were treated according to protocol with four different doses of OLT1177™ for 8 days (EudraCT: 2016-000943-14). Blood was drawn at baseline, days 3, 7 and 14 (7 days after finishing treatment). Haematology was evaluated as a marker of systemic inflammation. Plasma was collected for assessment of circulating cytokines. Peripheral blood mononuclear cells (PBMCs) were isolated and cultured under unstimulated or stimulated conditions with a TLR ligand in combination with MSU crystals after which intra- and extracellular cytokine production were assessed.

Results: Treatment of acute gout flares in humans with oral OLT1177™ demonstrates a reduction in white blood cell counts, mainly neutrophils, in all cohorts. In cohorts receiving 2000mg, 1000mg or 300mg, both circulating IL-1β and IL-6 and ex vivo IL-1β and IL-6 production by stimulated PBMCs were reduced during treatment with the strongest effect in the cohort with the highest dose OLT1177™. In unstimulated PBMCs on day 3, ratio of intracellular pro-IL-1β and IL-1β revealed inhibition of the NLRP3 inflammasome by oral OLT1177™ treatment. All these markers of inflammation are relevant parameters that correlate with target joint pain.

Conclusion: Oral OLT1177™, safe in humans, is a potential drug for the treatment of gout flares and other NLRP3 mediated diseases.


Disclosure: V. Kluck, None; T. Jansen, AbbVie, Celgene Corporation, 5, Grunenthal, Sobi, 8, Olatec, Grunenthal, 2; M. Janssen, None; I. Tengensdal, None; K. Schraa, None; M. Cleophas, None; D. Skouras, Olatec Therapeutics LLC; C. Marchetti, None; C. Dinarello, Olatec Therapeutics LLC; L. Joosten, Olatec Therapeutics LLC.

To cite this abstract in AMA style:

Kluck V, Jansen T, Janssen M, Tengensdal I, Schraa K, Cleophas M, Skouras D, Marchetti C, Dinarello C, Joosten L. Treatment with OLT1177™, an Oral NLRP3 Inflammasome Inhibitor, Reduces Systemic Inflammation During Gout Flares in Humans [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/treatment-with-olt1177-an-oral-nlrp3-inflammasome-inhibitor-reduces-systemic-inflammation-during-gout-flares-in-humans/. Accessed .
  • Tweet
  • Email
  • Print

« Back to 2019 ACR/ARP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/treatment-with-olt1177-an-oral-nlrp3-inflammasome-inhibitor-reduces-systemic-inflammation-during-gout-flares-in-humans/

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