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Juvenile dermatomyositis (JDM) is a systemic vasculopathy with weakness and rash, frequently exhibiting a chronic/polycyclic course, and treated with broad immunosuppression. An interferon (IFN) signature correlates with disease activity.1 Interferonopathies have been successfully targeted by janus kinase (JAK) inhibitors.2 3 We report the first comprehensive prospective evaluation of JAK inhibition (baricitinib) in JDM.
Four patients (5.8–20.7 years old), with chronically active JDM (≥3/6 core set measures)4 who had failed three to six immunomodulatory medications, were enroled on compassionate use study NCT01724580 (online supplementary methods, online supplementary table 1). Biologics other than intravenous immunoglobulin were washed out and other medications continued.
Subjects were assessed before and 4, 8, 12 and 24 weeks after starting baricitinib (4–8 mg/day divided two times per day) dosed by weight and renal function.3 Significant improvement was noted by week 4 in Physician Global Activity, Patient/Parent Global Activity, and Extramuscular Global Activity, and Cutaneous Dermatomyositis Disease Area and Severity Index (figure 1, online supplementary table 2). Two patients with baseline weakness improved by week 4 (ACR/EULAR Myositis Response Criteria) and showed clinically relevant improvement in Manual Muscle Testing-8 by week 8, confirmed by blinded MRI assessment (online supplementary figures 1 and 2). There was no significant change in muscle enzymes (online supplementary table 3), though some had variable elevations with stable/improved strength. Daily corticosteroids were decreased (0.28 to 0.18 mg/kg/day); other immunosuppressive medications were decreased/discontinued (online supplementary table 1). There were no flares/worsening requiring increased immunosuppression. There was no notable change in calcinosis (n=2).
Handling editor Josef S Smolen
Correction notice This article has been corrected since it published Online First. A symbol in the figure 1 legend has been corrected to †† and figure 1 replaced and the dosage information has been changed within the content.
Contributors HK acquired data, oversaw the clinical aspects of the study, reviewed and analysed data and wrote the first draft of the manuscript. HK, LGR and RAC designed the study and provided clinical expertise. RAC and HK oversaw regulatory aspects of the study. HK, SD, MOB, MM, MJ, MP, AAG, MS, BMF, DCP, EWC, LY, MM and AB acquired and interpreted clinical data. SJ, WLT, YS, LV and MG conducted experiments, acquired and analysed data. LA and JG analysed pharmacokinetic data. XL conducted and oversaw statistical analyses of study data. All authors reviewed and approved the final version of the manuscript.
Funding This research was supported by the Intramural Research Program of the NIH, NIAMS including the Translational Immunology Section, NIEHS (ZIAES101081), and CC. Eli Lilly and Company provided baricitinib, pharmacokinetic and BK virus testing, and support through a Cooperative Research and Development Agreement. Eli Lilly and Company is the sponsor of this expanded access program.
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting or dissemination plans of this research.
Patient consent for publication Parental/guardian consent obtained.
Ethics approval All subjects were enroled in expanded access program and natural history study approved by the National Institutes of Health Institutional Review Board, and all patients/parents provided informed consent as well as photography consent.
Provenance and peer review Not commissioned; externally peer reviewed.