695 Pityriasis rubra pilaris treated with guselkumab: Interim analysis of a single-arm trial

Abstract

Pityriasis rubra pilaris (PRP) is a rare inflammatory skin disorder characterized by generalized pruritic erythematous scaly plaques and waxy palmoplantar keratoderma with painful fissuring. PRP is a life-altering condition with severe detriment to patients’ quality of life, but as of yet there is no FDA-approved medication for the treatment of PRP. The exact pathogenesis of PRP is unclear, but previous studies have demonstrated the role of the IL-23/Th17 axis in the development of this condition. We are conducting an ongoing investigator-initiated single-arm trial to investigate the use of guselkumab, a monoclonal antibody against IL-23, in the treatment of PRP (clinicaltrials.gov identifier NCT03975153). The study cohort includes patients 18-99 years of age with moderate-to-severe PRP (body surface area ≥ 10%) and no major comorbidities. Subjects received guselkumab 100 mg subcutaneous injection according to the FDA-approved dosing schedule for psoriasis (weeks 0, 4, 12, and 20) and progress was tracked via both investigator- and patient- reported outcomes. The primary endpoint of the study was at week-24; to date, six subjects have completed 24 weeks of treatment. Results from this cohort were analyzed using two-tailed paired t tests. An intention-to-treat analysis was conducted. The study cohort is composed of 4 males and 2 females with a median age of 59.5 years. Mean clinician-assessed severity as measured by PASI decreased significantly from week-0 (31.4, SD=13.5) to week-24 (10.8, SD=10.5) (p=0.0159). Five of six patients experienced a greater than 50% improvement in PASI score, and one patient did not complete the trial due to lack of improvement. Patient-reported quality of life as measured by the Dermatology Life Quality Index (DLQI) was also significantly improved from week-0 (21.3, SD=5.7) to week-24 (9.5, SD=9.4) (p=0.0074). Interim results demonstrate the disease burden of untreated PRP and the dramatic improvement in PRP symptomology following a course of guselkumab therapy.