Treatment of Non Severe Hemophagocytosis Lymphohistiocytosis With ITACITINIB

This project aims to test the effectiveness of ITACITINIB in sporadic Hemophagocytosis Lymphohistiocytosis (HLHs). The existence of an IFN-γ signature, in HLHs, is a strong rational for testing the use of a JAK1 inhibitor in the treatment of HLHs. We hypothesize that ITACITINIB, an inhibitor of JAK-1, may be a therapeutic of interest in the treatment of non-severe HLHs in replacement of corticosteroids by inhibiting the production and effects of IFN-γ but also those of other pro-inflammatory cytokines. The use JAK-1 inhibitor instead of corticosteroids in patients with HLHs without any sign of severity is justified by its probable lesser toxicity and higher efficiency.

In this proof of concept study, because of the vital risk associated with severe HLH and the efficacy of Etoposide in this setting, we will first include only patients with moderate HLHs

Inclusion criteria

• Patients age > 18 years,
• Patient is willing to provide written informed consent prior to enrolment and agrees to follow the protocol
• Patient known to have systemic juvenile idiopathic arthritis are classified as having HLH
• Negative pregnancy test for woman of childbearing potential, woman of childbearing potential should have reliable contraception for the duration of the study
• Be either affiliated to, or a beneficiary of, a social security category

Exclusion criteria

• Organ failure: confusion, organic kidney failure KDIGO 2 criteria, liver failure (Factor V < 50%), heart failure, respiratory failure.
• Fibrinogen < 0.50 g/l, platelets <20G/L
• Indication to intensive care unit transfer on an organ failure requiring assistance (dialysis, Ventilation (assisted or VNI), shock regardless of the origin.
• Breastfeeding women
• Patient participating in another investigational therapeutic study
• Women with a positive pregnancy test or not willing to take contraceptive measures
• Known allergies, hypersensitivity, or intolerance to any of the ITACITINIB or excipients, or similar compounds
• Current or history of recurrent infections, including HBV, HCV
• Participants with active HBV or HCV infection that requires treatment or who are at risk for HBV reactivation (ie Positive HBs Ag serology)
• Candidates positive for HCV antibody and positive PCR RNA HCV
• HIV infection with positive viral charge
• Protected adults (including individual under guardianship by court order)
• Vulnerable adults, under a safeguard of justice measure
• Adults deprived of their liberty by judicial or administrative decision
• Persons under psychiatric care without their consent
• Persons admitted to social institution for purposes other this research
• Adults under legal protection (guardianship or curatorship)
• Persons unable to express their consent