Presenter of 1 Presentation
JAK-INHIBITOR TREATMENT OF INBORN ERRORS OF IMMUNITY WITH DYSREGULATED JAK/STAT SIGNALLING, AN ESID AND EBMT INBORN ERRORS WORKING PARTY STUDY
Abstract
Background and Aims
Inborn errors of immunity (IEI) with dysregulated JAK/STAT signalling can present with variable manifestations of severe immune dysregulation. Hematopoietic stem cell transplantation (HSCT) is potentially curative, however the reported treatment related mortality (TRM) of JAK/STAT patients is significant. Targeted therapies with JAK Inhibitors (JAKinib) offer a promising alternative and potentially TRM reducing bridging option. However, data on efficacy and adverse events (AE) of JAKinib treatment for IEI are limited.
Methods
Multicentre retrospective cohort study on patients with pathogenic variants in a JAK/STAT IEI-gene who have received JAKinib treatment for at least 3 months.
Results
66 patients (74% children) were included (41 STAT1-GOF, 21 STAT3-GOF, 1 STAT1-LOF, 1 STAT5B, 1 SOCS1, 1 JAK1-GOF). Ruxolitinib was the predominantly prescribed JAKinib (82%). Improvement of general well-being was observed in 91%. However, therapeutic responses varied among underlying diseases and disease manifestations. In 41% of patients, AE were observed (i.e. infections and weight gain). AE could generally be well controlled, leading to discontinuation of treatment in only 15% among patients who suffered AE. Currently, 76% patients are maintained on JAKinib (mean treatment observation 20 months) while 17% patients have received HSCT. Drug dosing and monitoring varies considerably between individual patients and centres.
Conclusions
Our study affirms that JAKinib are an effective and generally well tolerated therapy for patients with JAK/STAT-IEI. While there was variable efficacy for different disease manifestations, severe adverse events were rare. Our data will provide the basis for a consensus process to generate treatment recommendations and for the implementation of a prospective Jakinib treatment registry.