Upadacitinib monotherapy for treatment of pyoderma gangrenosum: A case series

Summary: Abstract Body: Pyoderma gangrenosum (PG) is a rare inflammatory disorder characterized by sterile neutrophilic infiltration of the epidermis or dermis, leading to painful and often debilitating skin lesions. Rates of disease vary widely, likely due to challenges in diagnosis, but it is estimated to affect approximately 58 people per million in the United States, with a median age of onset at 50 years and a higher prevalence among middle-aged individuals. Diagnosis is challenging due to its variable presentation and lack of definitive diagnostic criteria, while treatment typically relies on off-label drug use and is frequently complicated by relapses. Dysregulation of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway has been implicated in the pathogenesis of PG, and emerging evidence from limited case studies suggests potential efficacy of JAK inhibitors in its management. These medications have been approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of inflammatory disorders such as atopic dermatitis, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and Crohn’s disease. In this case series, we report the successful treatment of PG lesions using upadacitinib monotherapy, a second-generation selective JAK1 inhibitor with an improved safety profile compared to conventional therapies. Patients achieved complete reepithelialization of lesions and complete resolution of reported pain, demonstrating the great potential of upadacitinib for the safe and effective management of resistant and recurring PG lesions. These findings underscore the promise of JAK1 inhibitors as a targeted therapeutic option for PG, warranting further investigation in larger clinical trials. Deepika Narayanan¹, Mohamad R. Taha², Harrison P. Nguyen¹, Stephen K. Tyring^{1, 3} 1. Center for Clinical Studies, Texas, Webster, TX, United States. 2. College of Medicine, Texas A&M University System, College Station, TX, United States. 3. Department of Dermatology, The University of Texas Health Science Center at Houston John P and Katherine G McGovern Medical School, Houston, TX, United States. Clinical Research: Interventional Research