JAK inhibitors are effective in a subset of patients with juvenile dermatomyositis: a monocentric retrospective study.

Abstract

OBJECTIVE:

To evaluate the efficacy and safety of Janus kinase inhibitors (JAKis) in JDM.

METHODS:

We conducted a single-centre retrospective study of patients with JDM treated by JAKi with a follow-up of at least 6 months. Proportion of clinically inactive disease (CID) within 6 months of JAKi initiation was evaluated using PRINTO criteria and skin Disease Activity Score. Serum IFN-α concentration was measured by Simoa assay.

RESULTS:

Nine refractory and one new-onset patients with JDM treated with ruxolitinib (n = 7) or baricitinib (n = 3) were included. The main indications for treatment were refractory muscle involvement (n = 8) and ulcerative skin disease (n = 2). CID was achieved in 5/10 patients (two/two anti-MDA5, three/four anti-NXP2, zero/three anti-TIF1γ-positive patients) within 6 months of JAKi introduction. All responders could withdraw plasmatic exchange, immunoadsorption and other immunosuppressive drugs. The mean daily steroid dose decreased from 1.1 mg/kg (range 0.35-2 mg/kg/d) to 0.1 (range, 0-0.3, P = 0.008) in patients achieving CID, and was stopped in two. Serum IFN-α concentrations were elevated in all patients at the time of treatment initiation and normalized in both responder and non-responder. A muscle biopsy repeated in one patient 26 months after the initiation of JAKi, showed a complete restoration of muscle endomysial microvascular bed. Herpes zoster and skin abscesses developed in three and two patients, respectively.

CONCLUSION:

JAKis resulted in a CID in a subset of new-onset or refractory patients with JDM and may dramatically reverse severe muscle vasculopathy. Overall tolerance was good except for a high rate of herpes zoster infection.

• Authors: Tom Le Voyer, Cyril Gitiaux, François-Jérôme Authier, Christine Bodemer, Isabelle Melki, Pierre Quartier, Florence Aeschlimann, Arnaud Isapof, Jean Philippe Herbeuval, Vincent Bondet, Jean-Luc Charuel, Marie-Louise Frémond, Darragh Duffy, Mathieu P Rodero, Brigitte Bader-Meunier
• Journal: Rheumatology (Oxford, England) (Rheumatology (Oxford)) Vol. 60 Issue 12 Pg. 5801-5808 (12 01 2021) ISSN: 1462-0332 [Electronic] England
• PMID: 33576769 (Publication Type: Journal Article)
• Copyright: © The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: [email protected].

Chemical References

• Autoantibodies
• Azetidines
• Biomarkers
• Interferon-alpha
• Janus Kinase Inhibitors
• Nitriles
• Purines
• Pyrazoles
• Pyrimidines
• Sulfonamides
• ruxolitinib
• Janus Kinases
• baricitinib

Topics

• Adolescent
• Autoantibodies (blood, immunology)
• Azetidines (therapeutic use)
• Biomarkers (blood)
• Child
• Child, Preschool
• Dermatomyositis (blood, drug therapy, immunology)
• Female
• Humans
• Interferon-alpha (blood)
• Janus Kinase Inhibitors (therapeutic use)
• Janus Kinases
• Male
• Nitriles (therapeutic use)
• Purines (therapeutic use)
• Pyrazoles (therapeutic use)
• Pyrimidines (therapeutic use)
• Retrospective Studies
• Sulfonamides (therapeutic use)
• Treatment Outcome