TY - JOUR
T1 - Biological and clinical changes in a pediatric series treated with off-label jak inhibitors
AU - Pin, Alessia
AU - Tesser, Alessandra
AU - Pastore, Serena
AU - Moressa, Valentina
AU - Valencic, Erica
AU - Arbo, Anna
AU - Maestro, Alessandra
AU - Tommasini, Alberto
AU - Taddio, Andrea
N1 - Funding Information:
Funding: This work was supported by the Institute for Maternal and Child Health-IRCCS “Burlo Garofolo” in Trieste (Italy) RC #24/2017.
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/10/2
Y1 - 2020/10/2
N2 - Off-label use of medications is still a common practice in pediatric rheumatology. JAK inhibitors are authorized in adults in the treatment of rheumatoid arthritis, psoriatic arthritis and ulcerative colitis. Although their use is not authorized yet in children, JAK inhibitors, based on their mechanism of action and on clinical experiences in small series, have been suggested to be useful in the treatment of pediatric interferon-mediated inflammation. Accordingly, an increased interferon score may help to identify those patients who might benefit of JAK inhibitors. We describe the clinical experience with JAK inhibitors in seven children affected with severe inflammatory conditions and we discuss the correlation between clinical features and transcriptomic data. Clinical improvements were recorded in all cases. A reduction of interferon signaling was recorded in three out of seven subjects at last follow-up, irrespectively from clinical improvements. Other signal pathways with significant differences between patients and controls included upregulation of DNA repair pathway and downregulation of extracellular collagen homeostasis. Two patients developed drug-related adverse events, which were considered serious in one case. In conclusion, JAK inhibitors may offer a valuable option for children with severe interferon-mediated inflammatory disorders reducing the interferon score as well as influencing other signal pathways that deserve future studies.
AB - Off-label use of medications is still a common practice in pediatric rheumatology. JAK inhibitors are authorized in adults in the treatment of rheumatoid arthritis, psoriatic arthritis and ulcerative colitis. Although their use is not authorized yet in children, JAK inhibitors, based on their mechanism of action and on clinical experiences in small series, have been suggested to be useful in the treatment of pediatric interferon-mediated inflammation. Accordingly, an increased interferon score may help to identify those patients who might benefit of JAK inhibitors. We describe the clinical experience with JAK inhibitors in seven children affected with severe inflammatory conditions and we discuss the correlation between clinical features and transcriptomic data. Clinical improvements were recorded in all cases. A reduction of interferon signaling was recorded in three out of seven subjects at last follow-up, irrespectively from clinical improvements. Other signal pathways with significant differences between patients and controls included upregulation of DNA repair pathway and downregulation of extracellular collagen homeostasis. Two patients developed drug-related adverse events, which were considered serious in one case. In conclusion, JAK inhibitors may offer a valuable option for children with severe interferon-mediated inflammatory disorders reducing the interferon score as well as influencing other signal pathways that deserve future studies.
KW - Interferon signature
KW - Janus kinase inhibitors
KW - Juvenile idiopathic arthritis
KW - Juvenile systemic erythematosus lupus
KW - Juvenile systemic sclerosis
KW - Monogenic interferonopathies
KW - Off-label medications
KW - Pediatric rheumatology
KW - Transcriptomics
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U2 - 10.3390/ijms21207767
DO - 10.3390/ijms21207767
M3 - Article
C2 - 33092242
AN - SCOPUS:85093683316
VL - 21
SP - 1
EP - 29
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 20
M1 - 7767
ER -