Efficacy of oral JAK1 or JAK1/2 inhibitor for treating refractory pruritus in dystrophic epidermolysis bullosa: A retrospective case series

Abstract

Refractory pruritus is the most distressing, disease-related symptom in patients with dystrophic epidermolysis bullosa (DEB), inducing an itch-scratch-blister cycle. Chronic inflammation is a hallmark of DEB, thus upregulation of inflammatory cytokines and Janus kinase (JAK) signaling may play a role in DEB-related pruritus. We retrospectively reviewed the medical records of DEB patients with refractory pruritus who were treated with either baricitinib, a JAK1/2 inhibitor, or upadacitinib, a selective JAK1 inhibitor. Patients received baricitinib (4 mg) or upadacitinib (15 mg) once a day for 2-32 weeks. A total of 12 DEB patients (six recessive DEB and six dominant DEB) were included in this study. The mean +/- SD baseline pruritus visual analog scale (VAS) score was 7.5 +/- 1.7. Upadacitinib or baricitinib treatment resulted in a rapid and sustained decrease in itch. Four out of 12 patients (33.3%) and seven out of 10 patients (70%) showed a decrease of at least 3 points in the pruritus VAS score from baseline at weeks 2 and 4, respectively. The mean percentage changes from baseline in pruritus VAS scores at weeks 2 and 4 were -42.9% and -52.7%, respectively. Subgroup analysis showed greater reductions in the pruritus VAS score in the baricitinib group (n = 5) compared to the upadacitinib group (n = 7), and in patients with epidermolysis bullosa pruriginosa (n = 3) compared to other subtypes of DEB (n = 9); however, these differences did not reach statistical significance. Three out of 10 (33.3%) patients showed at least a 2-point reduction in pain intensity from baseline at week 4. Eight out of 12 patients (66.7%) also showed a reduction in the number of new blisters, which correlated with a reduction in the pruritus score. No patient discontinued treatment because of serious adverse events. Our results suggest that JAK1 or JAK1/2 inhibitors could be a promising treatment option for DEB-related pruritus. Long-term safety should be assessed in future studies.