P045 Tofacitinib Treatment in Refractory Juvenile Dermatomyositis: A Case Series

Abstract

Abstract Background Juvenile Dermatomyositis (JDM) is a systemic, autoimmune disease affecting the skin, blood vessels, and proximal skeletal muscles of juvenile individuals. A subset of JDM patients present with subclinical or resolved muscle involvement but continue to have skin disease. In these cases, first and second line treatments including glucocorticoids are sometimes insufficient for controlling the disease, necessitating escalation of treatment. Several recent studies have investigated the response of Tofacitinib, an oral Janus Kinase inhibitor approved for the treatment of rheumatoid arthritis, in DM patients and patients with inflammatory skin diseases Objectives Due to the reported ability of JAK inhibitors to suppress type 1 interferon (IFN) signalling, which is suspected to be upregulated in JDM, we evaluated the efficacy of treatment with Tofacitinib in four JDM patients. Methods Three patients with juvenile dermatomyositis without evidence of current muscle involvement and one patient with evidence of muscle involvement began treatment with Tofacitinib 5 mg daily after they had failed or had adverse effects to first- and second-line immunosuppressive agents. Their medical records were reviewed with improvement measured using the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) activity score. Throughout their treatment they were additionally monitored for improvement in markers of inflammation and muscle enzymes including CK, LDH, and aldolase. Patients were monitored for adverse effects to Tofacitinib. Results Three of four patients within the case series showed significant improvement of their CDASI scores over the initial first three months and two out of four patients showed continued improvement over the first six months. Patient #2 required use of Intravenous Immunoglobulin (IVIG) therapy in response to a flare despite continued use of Tofacitinib within the first six months. This patient also continues to require concomitant use of Hydroxychloroquine and IVIG however remains in skin remission. This patient has developed calcinosis despite having no active rash or muscle disease. TOF dose was increased to 5 mg bid for this patient. Patient #4 initially presented with mild skin disease. Other outcomes included significant improvement in arthritis with the addition of methotrexate. This patient also recieved a topical skin steroid injection by dermatology. Conclusion Tofacitinib is believed to play a role in the inhibition of IFN signalling pathways that are overactive in dermatomyositis. Three of the four patients within this retrospective study showed significant improvement of cutaneous disease with Tofacitinib use. Further controlled studies will show the utility of JAK inhibition in JDM.