baricitinib in the treatment of new-onset juvenile dermatomyositis (myocit)

Conditions: Juvenile Dermatomyositis

Summary: the myocit study aims to evaluate the efficacy and safety of baricitinib in association with corticosteroids in new-onset patients with juvenile dermatomyositis (jdm) in a phase ii trial with the objective to obtain a better efficacy than the conventional combination methotrexate (mtx) and corticosteroids over the 24 week study period. thus, the investigators hypothesize that baricitinib could be used as a first line treatment in all forms of dmj, including the most severe one, with a good safety profile.

juvenile dermatomyositis (jdm) is a rare and severe paediatric-onset idiopathic inflammatory myopathy, associated with significant morbidity and mortality. the combination of corticosteroids and methotrexate (mtx) is recommended in new-onset jdm according to one randomized trial. however, in this trial, treatment failures were reported in 13/46 (28%) patients and severe jdm, (cutaneous or gastrointestinal ulceration, interstitial pulmonary disease, cardiomyopathy) were not taken into account. these data emphasize the need for a more efficient first-line treatment. considering: 1) the strong implication of type ifn-i in the pathophysiology of jdm 2) the report of the efficacy and safety of jak inhibitors (jakis) (baricitinb, tofacitinib) in about 50 refractory dm patients, and 9 jdm, a trial which evaluates the efficacy and safety of baricitinib in combination with corticosteroids in new-onset jdm is warranted.

Eligibility criteria:
inclusion criteria: * patient aged 3-18 years with new-onset juvenile dermatomyositis, according to the enmc 2018 dermatomyositis classification criteria * muscle weakness at mmt and/or cmas (mmt \< 74 and/or cmas \< 45) * seropositivity or vaccination for chickenpox * for patients of childbearing age (following menarche) : negative βhcg and effective method of contraception (sexual abstinence, hormonal contraception, intrauterine device or hormone-releasing system, cap, diaphragm or sponge with spermicide, condom) until the 7 days after administration of the last dose of baricitinib * informed consent form signed by the patient or child' s parents patient affiliated to a social security regime exclusion criteria * amyopathic dermatomyositis (without muscle weakness) * inability to be treated by oral way or to take pills * previous treatment with jak inhibitor * previous treatment of jdm with immunosuppressive drugs or biologics other than corticosteroids. previous treatment with prednisone was allowed for no more than 1 month. * previous history of cancer * live vaccine within the 4 weeks before starting baricitinib therapy * current, or recent (\< 4 weeks prior to baseline) of active infections according to investigator appreciation, but necessarily, including hbv, hcv, hiv, tuberculosis. * positive blood cmv pcr * creatinine clearance \< 40 ml/min * lymphocytes \< 0,5x109 cell/l and neutrophils \< 1x109 cell/l * hemoglobin \< 8 g/dl * symptomatic herpes herpes simplex infection within 12 weeks prior to inclusion * history of thrombosis or considered at high risk of venous thrombosis by the investigator * presence of severe jdm-related involvements: cardiovascular (requiring vasopressive drug and/or intensive care unit), respiratory (requiring oxygen and/or intensive care unit), gastrointestinal (requiring abdominal surgery). * history of severe non-related jdm involvement: cardiovascular, respiratory, hepatic, gastrointestinal, endocrine, hematological, neurological or neuropsychiatric disorders or any other serious and/or instable illness that, in the opinion of the investigator, could constitute an unacceptable risk, when taking baricitinib. * actual or in project of pregrancy and breast-feeding until the 7 days after administration of the last dose of baricitinib * patient on ame (state medical aid) * participation in another interventional study involving human participants or being in the exclusion period at the end of a previous study involving human participants

Keywords: juvenile dermatomyositis baricitinib