Translating tissue expression of STAT 1, 3 and 6 in prurigo nodularis to clinical efficacy of oral tofacitinib - A prospective single-arm investigational study.

Abstract

Background Interleukin (IL)-4, IL-13, IL-17, IL-22 and IL-3 are overexpressed in prurigo nodularis (PN). They mediate their action via the Janus Kinase (JAK) Signal transducer and activator of transcription (STAT) pathway. Objectives Our aim was to study the expression of tissue STAT1, STAT3, and STAT6, as well as the efficacy of the JAK-STAT inhibitor, tofacitinib, in PN. Methods A prospective study was conducted in a tertiary care hospital. Patients with PN were recruited after excluding secondary causes. Pruritus was graded using Pruritus Grading System Score (PGSS). All cases underwent histological assessment using immunohistochemical markers for STAT1, STAT3, and STAT6 in both lesional and perilesional skin. Tofacitinib was initiated at a dose of 5 mg twice daily or 11 mg once daily and then tapered to a maintenance dose. The final PGSS at the time of data evaluation, as well as the occurrence of remissions and relapses, was assessed. Results The majority of the 17 patients included in the study had moderate to severe disease. Immunohistochemical analysis revealed marked tissue expression of STAT6 in 13 and STAT3 in 10 patients, while STAT1 expression was seen in only 4 patients [p < 0.05], suggesting a Th2/Th17 tissue response. The mean onset of action of tofacitinib was 11.2 ± 6.44 days and the mean duration of treatment was 5.6 ± 2.2 months. A significant reduction in PGSS was noted after treatment (66.1%, P value 0.0004). Fourteen of the patients maintained remission on low-dose therapy (5 mg OD or A/D) while one patient experienced a relapse. No serious adverse effects were noted. Limitation We could not study the tissue cytokines and the expression of STATs after achieving clinical response on oral tofacitinib. Conclusion The efficacy of tofacitinib in PN is based on its inhibitory effect on Th2 and Th17 cytokines, which is dependent on STAT6 and STAT3.