Baricitinib in Patients With Relapsing or naïve Dermatomyositis: a Multicenter Randomized Controlled Trial (BIRD)
Dermatomyositis (DM) is a rare and disabling condition with an important impairment of quality of life and possible life-threatening complications. Treatment is based on high doses of corticosteroids but this exposes patients to adverse events (cardiovascular mortality, glucocorticoids-induced muscle and skin damages). Corticosteroids taper is associated with disease relapses. Although there is no evidence from the literature, clinical practice guidelines recommends the use of DMARDs such as methotrexate. However, response is not complete and these DMARDS take time to act. The interferon type I (IFN-I) pathway is involved in the pathophysiology of DM. Janus kinase 1 and 2 transduces IFN-I signals. In addition, JAK2 inhibition enhances muscle repair and force generation. JAK 1/2 inhibitors permitted to dramatically and rapidly improve relapsing DM patients (n=4, case series). Our hypothesis is that Janus kinase 1 and 2 (JAK1/2) inhibitors (baricitinib) will permit to obtain dermatomyositis (DM) improvement with a steroid sparing effect as compared to usual care. Our primary objective is to evaluate the efficacy of baricitinib (JAK1/2 inhibitor) to obtain prednisone-free moderate improvement (ACR/EULAR ≥ 40) of DM as compared to placebo in addition to usual care. BIRD is a multicenter phase III double blind randomized placebo-controlled trial with two parallel arms (1:1). This is an add-on trial to usual care with rapid corticoid taper. This is a multicenter trial in different medical departments in hospitals across France in different regions. Out- and in patients will be recruited in hospital departments involved in management and diagnosis of DM: departments of dermatology, rheumatology and internal medicine.
• Adult subjects (≥ 18 years old) \< 65 years old
• Dermatomyositis defined according to the 239th ENMC criteria either naïve or non-naïve DM
• Active disease (ACR/EULAR criteria) defined as :
‣ Manual Muscle Testing (MMT-8) \<145/150 and at least two additional abnormal corset measurements (CSM): \>3/10 cm on Visual Analogue Scale (VAS) of patient global, physician global and extra-muscular disease activity, Health Assessment Questionnaire Disability Index \>0.25, or elevated muscle enzymes.
⁃ Or cutaneous CDASI \> 20 and at least two additional abnormal corset measurements (CSM): \>3/10 cm on Visual Analogue Scale (VAS) of patient global, physician global and extra-muscular disease activity, Health Assessment Questionnaire Disability Index \>0.25, or elevated muscle enzymes
• for relapsing/non naïve DM patients :
‣ in case of corticosteroid exposure patient must receive a stable dose \< 30 mg/d prednisone with or without additional immunosuppressive therapy for at least 4 weeks before the baseline visit.
⁃ Stable dose of immunosuppressive therapy for at least 3 months before
• Affiliation to a social security regime
• Written informed consent