Anifrolumab for adult patients with refractory juvenile dermatomyositis

Summary: Abstract Body: Juvenile dermatomyositis (JDM) is an autoimmune connective tissue disorder with a chronic, relapsing course that can persist into adulthood. Current therapies exhibit widely variable efficacy. While JDM pathogenesis remains incompletely understood, continuous activation of type-I interferon (IFN) signaling is thought to play a key role, leading to changes including activation and infiltration of CD4+ and CD8+ T-cells, mitochondrial dysfunction, microvascular remodeling, and reduced muscle stem-cell repair and proliferation. IFN activity has been shown to correlate with histological and clinical measures of disease activity. Anifrolumab, a monoclonal antibody that blocks the type I IFN receptor IFNAR1, has been approved for treatment of SLE and is currently undergoing a phase III trial in adult DM, with some case reports and series showing encouraging prospects. We report three female patients, ages 22, 24, and 48, who had failed to obtain durable control of cutaneous JDM through combinations of methotrexate, mycophenolate, hydroxychloroquine, intravenous/subcutaneous immune globulin, or prednisone. Two had also failed systemic janus kinase inhibitors (JAKi), two had failed rituximab, one had failed quinacrine, one had failed azathioprine, one had failed cyclophosphamide, and one had failed cyclosporine. After initiation of anifrolumab at 300 mg per month alongside existing therapies, each patient saw remarkable improvement in cutaneous disease. Each patient was able to reduce systemic glucocorticoids and taper other therapies, including cessation of prior intravenous or subcutaneous immune globulin in two cases and JAKi in one case. These encouraging results illustrate the relationship between type-I IFN modulation and JDM as well as the promise of anifrolumab as a rescue medication for refractory cases. As there are no current FDA-approved therapies for refractory cutaneous JDM, these cases also highlight the need for further systematic investigation into type-I IFN modulation in JDM therapy. Connor Buechler^{1, 2}, David Pearson¹ 1. Dermatology, University of Minnesota Medical School, Minneapolis, MN, United States. 2. Internal Medicine, University of Minnesota Medical School, Minneapolis, MN, United States. Adaptive and Auto-Immunity