Therapeutic outcomes across Janus kinase inhibitors in prurigo nodularis

Background Prurigo nodularis (PN) is a debilitating skin condition. When inadequate disease control is achieved or other systemic therapies are contraindicated, Janus kinase inhibitors (JAKis) may be considered, although real-world evidence remains limited.Objectives To investigate clinical findings and treatment outcomes among patients diagnosed with PN and treated with JAKis in a real-world setting.Methods Retrospective cohort study across 23 Italian tertiary referral hospitals. Patients with PN were eligible if aged >= 18 years and had received a JAKi with a minimum follow-up of 12 weeks. The primary outcome was defined as the proportion of patients achieving a reduction of >= 4 points from baseline in the Peak Pruritus Numerical Rating Scale score. Key secondary outcomes included the rates of patients reaching a significant reduction in Investigator Global Assessment of Prurigo Nodularis Stage (IGA PN-S) and Investigator Global Assessment of Prurigo Nodularis Activity (IGA PN-A) scores.Results Of the total, 71 patients met the inclusion criteria. At week 16, the proportion of patients achieving the primary outcome was 94% for upadacitinib [n = 52/55; 95% confidence interval (CI) 87-100%], 83% for abrocitinib (n = 10/12; 95% CI 52-98%) and 100% for baricitinib (n = 4/4; 95% CI 40-100%), with results sustained at week 24. An IGA PN-A score of 0/1 was achieved in 90% of patients treated with upadacitinib and abrocitinib and in 50% of those on baricitinib by week 24. Improvements were observed across all other secondary outcomes assessed, with no safety concerns reported.Conclusions This study suggests that JAKis can achieve clinically meaningful outcomes in PN irrespective of atopic background, supporting their use across diverse patient profiles. Further research is warranted to validate these observations and explore their long-term effects.Prurigo nodularis (PN) is a debilitating condition marked by raised, intensely itchy, often painful nodules on the skin. When inadequate disease control is achieved or other systemic therapies are contraindicated, Janus kinase inhibitors (JAKi) may be considered in its management, although evidence supporting their therapeutic potential remains limited. This retrospective cohort study shows that upadacitinib, abrocitinib and baricitinib achieved clinically meaningful outcomes in treating PN without raising any safety concerns. Our findings indicate that JAKi may be considered for treating PN, regardless of atopic background, supporting their use across diverse patient profiles in clinical practice. Further research is warranted to validate these observations and explore their long-term effects.