PN is a chronic inflammatory skin disease characterised by intensely itchy lesions resulting from chronic scratching. The condition has been linked to inflammatory pathways involving the JAK/STAT signalling axis, specifically JAK1. This was the rationale for Dr Shawn Kwatra (Johns Hopkins University School of Medicine, MD, USA) and colleagues to test the selective JAK1 inhibitor povorcitinib in a 40-week phase 2 study (NCT05061693) to assess its long-term efficacy and safety in patients with PN.
The randomised, double-blind trial included 146 participants with moderate-to-severe PN who were treated with once-daily povorcitinib at 3 different doses (i.e. 15 mg, 45 mg, or 75 mg) for 16 weeks, followed by a 24-week extension phase. The primary endpoint was a ≥4-point reduction in the Itch Numerical Rating Scale (itch NRS4) at week 16, which is considered clinically relevant. Moreover, secondary endpoints included the time to itch NRS4 and the percentage of participants achieving Investigator Global Assessment (IGA)-Treatment Success (TS) of PN lesions .
At week 16, the itch NRS4 endpoint was met in 36% of participants on 15 mg povorcitinib, 44% on 45 mg, and 57% on 75 mg, compared with 8% in the placebo group (all P<0.01). In the subsequent single-blind extension period, composite responders (itch NRS4 and IGA-TS) were treated with 45 mg povorcitinib for another 24 weeks, whereas partial or non-responders received a 75 mg dose until week 40. Most responders retained the itch NRS4 response, including those that went from 75 mg in the double-blind phase to 45 mg in the extension period, and 88% of responders at week 16 achieved both endpoints (i.e. itch NRS4 response and IGA-TS) at week 40.
The study also showed that participants in the composite non-responder group improved during the extension period: 34% did show a NRS4 response at week 16, whereas 70% showed a response by week 40 when switched to 75 mg povorcitinib, highlighting the importance of longer-term treatment. This is particularly true for nodule improvement. Regarding this endpoint, only 11% in the composite non-responder group achieved an IGA-TS in week 16, compared with 51% in week 40. “Itch improvement happens faster, and many of these skin lesions can take a little longer to improve,” Dr Kwatra commented.
Safety was generally good, with few serious adverse events reported. Therefore, povorcitinib is a promising novel oral treatment for patients with PN, with the potential for early and long-term disease control.
Medical writing support was provided by Dr Susanne Kammerer