Abstract
JAK-inhibitors are small molecules blocking the JAK-STAT pathway that have proven effective in the treatment of different immune-mediated diseases in adults and juvenile idiopathic arthritis (JIA).Aim of StudyTo evaluate the safety and efficacy of tofacitinib in children with different rheumatic diseases.Material and MethodsWe extracted information from 24 children with the following diagnosis: JIA (n = 15), undifferentiated systemic autoinflammatory diseases (SAIDs) (n = 7), and juvenile dermatomyositis (JDM) (n = 2) who have been treated with tofacitinib for a period of longer than 6 months. The treatment outcomes were classified according to the opinion of the attending physicians as having a complete response (CR), i.e., the absence of disease activity, or a partial response (PR)—a significant improvement of symptoms and disease activity, or no response (NR)—no changes in disease activity.ResultsCR was achieved in 10/24 patients; 7/15 among JIA patients, 1/2 among JDM patients, 4/7 among SAID patients, and PR in 5/15 of JIA, 1/2 of JDM, and 3/7 of SAID patients. Three non-responders with JIA discontinued tofacitinib. Corticosteroids were successfully tapered off in 11/14 patients and discontinued in 2/14 patients. Four patients had side effects not requiring treatment discontinuation: liver enzyme elevation (n = 2), hypercholesterolemia (n = 1), lymphadenitis (n = 1).ConclusionJAK-inhibitors are effective new therapies for the treatment of multiple immune-mediated diseases. Our experience has shown the best results in patients with JIA and JIA-associated alopecia, and type I interferonopathies. More data from randomized controlled clinical trials are needed to use JAK-inhibitors safely in pediatric rheumatic diseases.
Highlights
A JAK-STAT signaling pathway is involved in the regulation of cell proliferation and differentiation, apoptosis, and immune signaling [1]
The clinical and laboratory data from 24 children, who had been treated with tofacitinib for longer than 6 months were included in this retrospective case series study
Patients were divided into three groups: juvenile idiopathic arthritis (JIA), juvenile dermatomyositis (JDM), and undifferentiated systemic autoinflammatory diseases (SAIDs)
Summary
A JAK-STAT signaling pathway is involved in the regulation of cell proliferation and differentiation, apoptosis, and immune signaling [1]. Dysregulation in the JAK-STAT pathway has been implicated in the pathogenesis of a number of diseases: infections and sepsis, chronic arthritis, inflammatory bowel disease, multiple sclerosis, tumors, and others [2, 3]. Therapies targeting the JAK-STAT pathway have been promising in the treatment of various immunological and inflammatory conditions [3]. The success of the use of kinases-blockers in oncology [4] has paved the way for the use of JAK-inhibitors in rheumatic diseases, especially in rheumatoid arthritis: ruxolitinib [5], tofacitinib [6] and baricitinib [7]. The indications of JAK-inhibitors for pediatric rheumatic diseases other than juvenile idiopathic arthritis, the optimal dosage, and safety have not been fully evaluated and recommendations are still pending
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
