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: 1415

Emapalumab, an Anti-Interferon Gamma Monoclonal Antibody in Two Patients with NLRC4-Related Disease and Severe Hemophagocytic Lymphohistiocytosis (HLH)

Claudia Bracaglia1, Giusi Prencipe1, Antonella Insalaco1, Ivan Caiello2, Giulia Marucci1, Raffaele Pecoraro3, Manuela Pardeo1, Pavla Dolezalova4, Sarka Fingerhutova4, Maria Ballabio5, Cristina de Min5 and Fabrizio De Benedetti6, 1Division of Rheumatology, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy, 2Division of Rheumatology, IRCCS Ospedale Pediatrico Bambino Gesù, Roma, Italy, 3Pediatric Department, La Sapienza University of Rome, Rome, Italy, 4Paediatric Rheumatology Unit, General University Hospital in Prague and 1st Faculty of Medicine, Charles University, General University Hospital in Prague and 1st Faculty of Medicine, Prague, Czech Republic, 5NovImmune S.A., Geneva, Switzerland, 6IRCCS Ospedale Pediatrico Bambino Gesù, Roma, Italy

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: Autoinflammatory Disease, interferons and macrophage activation syndrome

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

Date: Monday, October 22, 2018

Title: Pediatric Rheumatology – Clinical Poster II: Autoinflammatory Disorders, Scleroderma, and Miscellaneous

Session Type: ACR Poster Session B

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

Background/Purpose: Interferon gamma (IFNγ) plays a pathogenic role in primary and secondary HLH. An ongoing phase 2/3 trial with emapalumab in primary HLH provides encouraging preliminary data and a pilot trial in MAS in the context of sJIA has just been initiated. Gain-of-function mutations in NLRC4 are associated with a distinct autoinflammatory syndrome, with recurrent HLH.

Methods: We report safety and efficacy of emapalumab treatment in 2 patients carrying de novo missense mutations in NLRC4, with severe early onset HLH. Cytokine levels were measured by multiplex assay and by specific ELISAs and expression of IFNγin freshly isolated PBMCs by cytometry.

Results: Pt 1. Caucasian male, presented, at age 20 days, fever and rash and progressively developed clinical and laboratory features of HLH leading to multi-organ failure. A de novo missense mutation in NLRC4 (T337N) was found. High-dose glucocorticoids and cyclosporine-A (CyA) led only to partial improvement. A sepsis triggered HLH reactivation. Emapalumab was started on background of dexamethasone (13.6mg/m2) and CyA. After 3 months, the child was discharged in excellent conditions. Infections resolved during treatment with emapalumab. After 7 months of emapalumab treatment, all therapies, including emapalumab, were discontinued, without signs of HLH reactivation. Pt 2. This is 16 months old Caucasian boy with recurrent HLH and vasculitic skin lesions, since 1 month of life, secondary to a de novo missense mutation in NLRC4 (I343N). His disease was not controlled despite treatment with repeated methylprednisolone pulses and chronic daily glucocorticoid therapy, CyA and anakinra (ranging from 5 to 25 mg/kg/day). When anakinra was withdrawn prior to start emapalumab he immediately developed high-grade fever, skin rash with vasculitic lesions and diarrhea with laboratory features of HLH. Emapalumab was started on background of methylprednisolone and CyA with rapid resolution of fever and improvement in biochemical parameters. During emapalumab treatment the patient resolved his initial HLH flare and presented two HLH episodes of mild intensity controlled with moderate intensification of glucocorticoid therapy. These episodes were triggered by systemic infections caused by pathogens translocated from the gut. His diarrhea persisted with low grade inflammation; emapalumab was eventually withdrawn after 3 months. His subsequent course was characterized by additional mildepisodes of HLH. In both patients increased production of IFNγwas demonstrated by high levels of CXCL9 (pt.1: 5670 pg/ml, pt.2: 3310 pg/ml), a chemokine induced specifically by IFNγ, by increased IFNγ expression in NK cells and CD8T cells, and by presence of high levels of total IFNγ bound to circulating emapalumab.

Conclusion: In both patients, treatment with emapalumab was well tolerated, no safety concerned emerged, normalization of all HLH clinical and laboratory abnormalities was achieved. Pt. 1 showed no disease reactivation even in the absence of treatments In pt. 2 IFNγ neutralization has provided control of HLH, while his underlying disease and, in particular, gut inflammation and gut colonization by MDR pathogens remained unchanged.


Disclosure: C. Bracaglia, None; G. Prencipe, None; A. Insalaco, None; I. Caiello, None; G. Marucci, None; R. Pecoraro, None; M. Pardeo, None; P. Dolezalova, None; S. Fingerhutova, None; M. Ballabio, Novimmune SA, 3; C. de Min, Novimmune SA, 3; F. De Benedetti, Abbvie, Sobi, Novimmune, Roche, Novartis, Sanofi, UCB, Pzifer, 2.

To cite this abstract in AMA style:

Bracaglia C, Prencipe G, Insalaco A, Caiello I, Marucci G, Pecoraro R, Pardeo M, Dolezalova P, Fingerhutova S, Ballabio M, de Min C, De Benedetti F. Emapalumab, an Anti-Interferon Gamma Monoclonal Antibody in Two Patients with NLRC4-Related Disease and Severe Hemophagocytic Lymphohistiocytosis (HLH) [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/emapalumab-an-anti-interferon-gamma-monoclonal-antibody-in-two-patients-with-nlrc4-related-disease-and-severe-hemophagocytic-lymphohistiocytosis-hlh/. 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 2018 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/emapalumab-an-anti-interferon-gamma-monoclonal-antibody-in-two-patients-with-nlrc4-related-disease-and-severe-hemophagocytic-lymphohistiocytosis-hlh/

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