| Title: |
Myositis-specific autoantibody subtypes are associated with response to Janus kinase inhibitors in patients with juvenile dermatomyositis |
| Authors: |
Bader-Meunier, Brigitte; Moreau, Thomas; Aeschlimann, Florence; Authier, François-Jérome; Charuel, Jean Luc; Jouen, Fabienne; Boyer, Olivier; Bodemer, Christine; Welfringer-Morin, Anne; Bondet, Vincent; Fournier, Benjamin; Quartier, Pierre; Frémond, Marie-Louise; Foray, Anne-Perrine; Sanchez, Carlos; Duffy, Darragh; Gitiaux, Cyril; Rodero, Mathieu, P |
| Contributors: |
Hôpital Necker - Enfants Malades AP-HP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP); Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163); Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité); Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601); Institut de Chimie - CNRS Chimie (INC-CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité); Immunologie Translationnelle - Translational Immunology lab; Institut Pasteur Paris (IP)-Université Paris Cité (UPCité); University Children's Hospital Basel, Switzerland; Hôpital Henri Mondor; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Henri Mondor Créteil; Groupe Henri Mondor-Albert Chenevier-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Henri Mondor-Albert Chenevier-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12); CHU Pitié-Salpêtrière AP-HP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU); Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices (PANTHER); Université de Rouen Normandie (UNIROUEN); Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM); Neurogénétique et neuroinflammation = Neurogenetics and neuroinflammation (Equipe Inserm U1163); Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité); Centre Hospitalier Lyon Sud CHU - HCL (CHLS); Hospices Civils de Lyon (HCL); This work was supported by a research grant from Agence Nationale de la Recherche (ANR) via project JDMINF2 (ANR-21-CE17-0025).; ANR-21-CE17-0025,JDMINF2,Dérégulation de la voie de l'interféron de type I dans la dermatomyosite juvénile: mieux comprendre la physiopathologie pour mieux identifier de nouveaux biomarqueurs pronostiques(2021) |
| Source: |
ISSN: 1462-0324. |
| Publisher Information: |
CCSD; Oxford University Press (OUP) |
| Publication Year: |
2025 |
| Collection: |
Inserm: HAL (Institut national de la santé et de la recherche médicale) |
| Subject Terms: |
type 1 interferon; Janus kinase inhibitors; myositis specific Abs; juvenile dermatomyositis; [SDV]Life Sciences [q-bio] |
| Description: |
International audience ; Objectives To evaluate the efficacy and safety of Janus kinase inhibitors (JAKi) in a monocentric series of patients with JDM and to identify factors associated with the achievement of clinically inactive disease (CID). Methods Single-centre retrospective study of 39 JDM patients treated with JAKi for at least 6 months. The proportion of patients achieving CID within 6 months after initiation of JAKi was assessed using the PRINTO criteria and the Skin Disease Activity Score. Type 1 IFN gene signature, serum IFN-α and IFN-β protein titres were measured as potential response biomarkers. Results Thirty-nine patients with JDM were included. Partial or complete CID was achieved in 32/39 (82%) patients after 6 months of treatment. In responders, the mean steroid dose decreased from 1 to 0 mg/kg/day (P = 0.001) and all other medications were withdrawn. In multivariable analysis, the presence of anti–transcriptional intermediary factor 1 gamma (anti-TIF1γ) Abs was the only factor at JDM onset associated with the absence of CID (P < 0.001). A significant decrease in the median Type 1 IFN score and serum IFN-α from the diagnosis of JDM to the 6-month follow-up was observed only in patients with CID. JAKi-related adverse events consisted of infections in nine patients (including five herpes zoster infections) and weight gain in three patients. Conclusions JAKi induced CID in the majority of new-onset and refractory JDM patients, except in a subset of patients with refractory TIF1γ-positive JDM. Overall tolerance was acceptable. These results need to be validated in a larger prospective international cohort study. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
https://pasteur.hal.science/pasteur-05120578; info:eu-repo/semantics/altIdentifier/pmid/40411753; PUBMED: 40411753 |
| DOI: |
10.1093/rheumatology/keaf214 |
| Availability: |
https://pasteur.hal.science/pasteur-05120578; https://pasteur.hal.science/pasteur-05120578v1/document; https://pasteur.hal.science/pasteur-05120578v1/file/Manuscrit%20auteur%20accepte-pasteur-05120578.pdf; https://doi.org/10.1093/rheumatology/keaf214 |
| Rights: |
https://creativecommons.org/licenses/by-nc/4.0/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.F1B123B0 |
| Database: |
BASE |