Author:
Deyà-Martínez Angela,Rivière Jaques G.,Roxo-Junior Pérsio,Ramakers Jan,Bloomfield Markéta,Guisado Hernandez Paloma,Blanco Lobo Pilar,Abu Jamra Soraya Regina,Esteve-Sole Ana,Kanderova Veronika,García-García Ana,Lopez-Corbeto Mireia,Martinez Pomar Natalia,Martín-Nalda Andrea,Alsina Laia,Neth Olaf,Olbrich Peter
Abstract
Abstract
Introduction
Since the first description of gain of function (GOF) mutations in signal transducer and activator of transcription (STAT) 1, more than 300 patients have been described with a broad clinical phenotype including infections and severe immune dysregulation. Whilst Jak inhibitors (JAKinibs) have demonstrated benefits in several reported cases, their indications, dosing, and monitoring remain to be established.
Methods
A retrospective, multicenter study recruiting pediatric patients with STAT1 GOF under JAKinib treatment was performed and, when applicable, compared with the available reports from the literature.
Results
Ten children (median age 8.5 years (3–18), receiving JAKinibs (ruxolitinib (n = 9) and baricitinib (n = 1)) with a median follow-up of 18 months (2–42) from 6 inborn errors of immunity (IEI) reference centers were included. Clinical profile and JAKinib indications in our series were similar to the previously published 14 pediatric patients. 9/10 (our cohort) and 14/14 patients (previous reports) showed partial or complete responses. The median immune deficiency and dysregulation activity scores were 15.99 (5.2–40) pre and 7.55 (3–14.1) under therapy (p = 0.0078). Infection, considered a likely adverse event of JAKinib therapy, was observed in 1/10 patients; JAKinibs were stopped in 3/10 children, due to hepatotoxicity, pre-HSCT, and absence of response.
Conclusions
Our study supports the potentially beneficial use of JAKinibs in patients with STAT1 GOF, in line with previously published data. However, consensus regarding their indications and timing, dosing, treatment duration, and monitoring, as well as defining biomarkers to monitor clinical and immunological responses, remains to be determined, in form of international prospective multicenter studies using established IEI registries.
Funder
Consejería de Salud, Junta de Andalucía
Agencia de Innovación y Desarrollo de Andalucía
Instituto de Salud Carlos III
Ministerstvo Zdravotnictví Ceské Republiky
Departament de Salut, Generalitat de Catalunya
Fundación BBVA
Fundación de la Sociedad Española de Alergología e Inmunología Clínica
Universidad de Sevilla
Publisher
Springer Science and Business Media LLC
Subject
Immunology,Immunology and Allergy
Cited by
31 articles.
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