Janus Kinase (Jak) Inhibition With Baricitinib In Refractory Juvenile Dermatomyositis

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.\n\nFour 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.### Supplementary data\n\n[annrheumdis-2020-218690supp001.pdf]\n\nSubjects 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).\n\n\n\nFigure 1 \nChange in disease activity and pharmacodynamic markers on baricitinib treatment. (A–D) Multiple clinical assessments are shown at …