The following is a summary of “JAK inhibitor treatment for inborn errors of JAK/STAT signaling: An ESID/EBMT-IEWP retrospective study,” published in the January 2024 issue of Allergy & Immunology by Fischer, et al.
Inborn errors of immunity (IEI) characterized by dysregulated JAK/STAT signaling exhibit diverse manifestations of immune dysregulation and susceptibility to infections. While hematopoietic stem cell transplantation (HSCT) offers a potentially curative approach, initial outcomes were unsatisfactory. JAK inhibitors (JAKi) present a targeted therapeutic option that could serve as an alternative or a bridge to HSCT. However, limited data exist regarding their current use, treatment efficacy, and adverse events. For a study, researchers sought to assess the present off-label utilization of JAKi for JAK/STAT IEI among centers affiliated with the European Society for Immunodeficiencies (ESID) and the European Society for Blood and Marrow Transplantation (EBMT) Inborn Errors Working Party (IEWP).
A multicenter retrospective study was conducted involving patients with genetic disorders characterized by hyperactive JAK/STAT signaling who underwent JAKi treatment for a minimum of 3 months.
They evaluated 69 patients (72% children) comprising various subtypes, including 45 STAT1 gain of function (GOF), 21 STAT3-GOF, and others. Ruxolitinib was the predominantly prescribed JAKi (80%). Overall, JAKi therapy led to clinical symptom improvement (partial or complete remission) in 87% of STAT1-GOF and 90% of STAT3-GOF patients. Dosing and monitoring regimens varied significantly. Response rates and time to response differed among diseases and manifestations. Adverse events, predominantly mild (grade I-II) and transient, were observed in 38% of patients, with infections and weight gain being common. At the last follow-up, 74% of patients were still on JAKi treatment, with 11 patients undergoing HSCT following prior JAKi bridging therapy, resulting in 91% overall survival.
The findings suggested that JAKi may be highly effective in treating symptomatic JAK/STAT IEI patients. Prospective studies were needed to determine optimal JAKi dosing for diverse clinical presentations and age groups.
Reference: jacionline.org/article/S0091-6749(23)01390-8/abstract