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: 080

Therapeutic Interferon Gamma Neutralization with Emapalumab in Patients with NRLC4- and CDC42-Associated Diseases Characterized by Recurrent and Severe Hemophagocytic Lymphohistiocytosis

Claudia Bracaglia1, Antonella Insalaco 1, Giulia Marucci 1, Manuela Pardeo 1, Emanuela Sacco 1, Virginia Messia 1, Giusi Prencipe 1, Ivan Caiello 1, Sarka Fingerhutova 2, Pavla Dolezalova 2, Veronica Asnaghi 3, Maria Ballabio 3, Cristina de Min 3 and Fabrizio De Benedetti 1, 1Division of Rheumatology, IRCCS Ospedale Pediatrico Bambino Gesu', Rome, Italy, 2Paediatric Rheumatology and Autoinflammatory Diseases Unit, General University Hospital, Prague, Czech Republic, 3Swedish Orphan Biovitrum AG (Sobi), Basel, Switzerland

Meeting: 2020 Pediatric Rheumatology Symposium

Keywords: Autoinflammatory Disease, interferons, macrophage activation syndrome, treatment

  • Tweet
  • Click to email a link to a friend (Opens in new window) Email
  • Click to print (Opens in new window) Print
Session Information

The 2020 Pediatric Rheumatology Symposium, originally scheduled for April 29 – May 2, was postponed due to COVID-19; therefore, abstracts were not presented as scheduled.

Date: Friday, May 1, 2020

Title: Poster Session 2

Session Type: ACR Abstract Session

Session Time: 5:00PM-6:00PM

Background/Purpose: Interferon gamma (IFNγ) is a pivotal mediator of HLH. Emapalumab (a fully human anti-IFNγ monoclonal antibody) is efficacious in patients with primary HLH. In autoinflammatory diseases (AID), elevated IL-18 is considered a predisposing factor for secondary HLH, being a costimulus for IFNγ production. IL-18-transgenic or IL18BP-deficient mice, when triggered with toll-like receptor ligands, develop severe HLH; and neutralization of IFNγ leads to reversal of disease, supporting the role of IFNγ as the final downstream mediator.

Methods: We report the results of treatment with emapalumab (Table 1) in compassionate use in 2 patients with NLRC4- and in 1 patient with CDC42-associated AID. Cytokine levels, IFNγ expression, and HLH clinical and laboratory parameters were assessed.

Results: Levels of IL-18 were markedly increased ( >100,000 pg/mL) in all 3 patients, regardless of whether HLH was present at the time of sampling (Table 1). During HLH flares, increased IFNγ production was demonstrated by high CXCL9 levels (Table 1), which were strictly related to ferritin levels, and by increased IFNγ expression in NK cells and CD8T cells. Patient 1 (NLRC4 de novo pT337N) and patient 2 (NLRC4 de novo pI343N) presented with neonatal onset of autoinflammation and severe recurrent HLH. At 4 months of age, patient 1 experienced an HLH reactivation, with multiple organ failure requiring intensive care unit admission. Emapalumab (1 mg/Kg every 3 days), added to ongoing dexamethasone and cyclosporin A, led to HLH resolution (Figure 1). After 7 months, all therapies, including emapalumab, were discontinued, without HLH reactivation during a 4-year follow-up. In patient 2, emapalumab (1 mg/kg every 3 days for 5 doses and then 3 mg/Kg every 3 days for 3 months) was added to ongoing glucocorticoid and cyclosporin A during full-blown HLH, with prompt resolution (Figure 1). During emapalumab treatment, two mild HLH episodes occurred that were controlled with moderate intensification of glucocorticoids. Patient 3 (de novo pR186C) presented with neonatal onset of cytopenia, autoinflammation, rash, and recurrent HLH. A severe HLH flare, occurring while on anakinra and glucocorticoids, and requiring ICU admission because of multiple organ failure, was successfully treated with the addition of emapalumab (1 mg/kg for the first dose and then increased to 3 mg/kg every 3 days for 15 days) (Figure 1). She underwent successful hematopoietic stem cell transplantation.

Conclusion: In these 3 patients with monogenic AID associated with high IL-18 levels, HLH flares unresponsive to high-dose glucocorticoids were successfully controlled with emapalumab. Treatment was well tolerated, with no safety concerns.

Table 1: Levels of total IL_18, of the IFNγ_related chemokine CXCL9, and of ferritin before, during, and after administration of emapalumab.

Figure 1: Ferritin levels following treatment with emapalumab. Shaded are reflects the normal range.


Disclosure: C. Bracaglia, None; A. Insalaco, None; G. Marucci, None; M. Pardeo, None; E. Sacco, None; V. Messia, None; G. Prencipe, None; I. Caiello, None; S. Fingerhutova, None; P. Dolezalova, None; V. Asnaghi, SOBI, 1; M. Ballabio, SOBI, 1; C. de Min, SOBI, 1; F. De Benedetti, Novartis, 1, 2, Novimmune, 1, Sobi, 1, 2, Roche, 1, 2, Pfizer, 1, Sanofi, 1, AbbVie, 1, Novimmune/Sobi, 1.

To cite this abstract in AMA style:

Bracaglia C, Insalaco A, Marucci G, Pardeo M, Sacco E, Messia V, Prencipe G, Caiello I, Fingerhutova S, Dolezalova P, Asnaghi V, Ballabio M, de Min C, De Benedetti F. Therapeutic Interferon Gamma Neutralization with Emapalumab in Patients with NRLC4- and CDC42-Associated Diseases Characterized by Recurrent and Severe Hemophagocytic Lymphohistiocytosis [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 4). https://acrabstracts.org/abstract/therapeutic-interferon-gamma-neutralization-with-emapalumab-in-patients-with-nrlc4-and-cdc42-associated-diseases-characterized-by-recurrent-and-severe-hemophagocytic-lymphohistiocytosis/. Accessed .
  • Tweet
  • Click to email a link to a friend (Opens in new window) Email
  • Click to print (Opens in new window) Print

« Back to 2020 Pediatric Rheumatology Symposium

ACR Meeting Abstracts - https://acrabstracts.org/abstract/therapeutic-interferon-gamma-neutralization-with-emapalumab-in-patients-with-nrlc4-and-cdc42-associated-diseases-characterized-by-recurrent-and-severe-hemophagocytic-lymphohistiocytosis/

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