Effectiveness of Upadacitinib in Refractory Skin and Rapidly Progressive Lung Manifestations of Myositis

Background Limited data are available on the use of Upadacitinib in idiopathic inflammatory myositis, as most available studies have focused on tofacitinib as a therapeutic option to target the interferon pathway.[1,2] Here, we report 2 cases demonstrating the use of Upadacitinib in different disease domains of idiopathic inflammatory myositis including severe lung and skin involvement. Case Report The first patient is a 35-year-old man presented with MDA5 positive rapidly progressive interstitial lung disease ILD, mediastinal mass and ulceration of the dorsum of the fingers. He experienced 2 hospital admissions for lung flares prior to full diagnosis. He was treated with mycophenolate mofetil and prednisone but attempts to taper prednisone resulted in worsening pulmonary symptoms. He then developed a spontaneous pneumothorax and ILD flare and was admitted for addition of rituximab (1g on day 0 and day14) along with IVIG. Despite treatment, he remained oxygen-dependent and was placed on the lung-transplant waiting list. Upadacitinib was initiated 3 months later, replacing mycophenolate mofetil. A follow-up CT chest after approximately 1 month of upadacitinib demonstrated resolution of dense inflammatory opacites with residual fibrosis, and he successfully waned off supplemental oxygen. He currently does not require urgent consideration for transplant. The second patient is a 54-year-old with dermatomyositis presented with severe cutaneous manifestations including Gottron’s papules, heliotrope rash, and mechanic’s hands. She had previously received multiple therapies: methotrexate, azathioprine, mycophenolate mofetil, hydroxychloroquine, IVIG (discontinued due to migraines), and abatacept with persistent disease activity and difficulty tapering prednisone. Upadacitinib was initiated, leading to marked improvement of her skin lesions and successful discontinuation of Prednisone. She remained in remission for approximately 3 years before developing mild cutaneous recurrence suggesting a disease flare. Discussion: Conclusion Addition of Upadacitinib may represent a promising therapeutic option for idiopathic inflammatory myositis, demonstrating efficacy in the different disease domains of lung and skin in patient’s refractory to standard therapy, potentially by targeting the interferon pathway. References [1.] Beckett M. RMD Open 2024;10:e003837. [2.] Uzunhan Y. Eur Respir J 2025;66:2500446.