Guselkumab in the Treatment of Pityriasis Rubra Pilaris (PRP)

15 patients with PRP will be treated with guselkumab for 20 weeks to determine safety and efficacy. Participants are required to travel to Portland, OR only for the first visit, week-4 visit, and week-24 visit. 3 visits in between these times and one follow up visit may be performed by secure videoconferencing.

Pityriasis rubra pilaris (PRP) is a rare and poorly understood severe inflammatory skin disease characterized by widespread (often full-body) redness and flaking of the skin, painful thickening and cracking of the palms and soles, hair loss, crumbling nails, and severe skin itching and burning.

There is no FDA-approved therapy for this rare disease and the commonly used medications do not work for many patients. There is some evidence that interleukin (IL)-23 may be too high in the skin of PRP patients. Ixekizumab is an injectable medication that blocks IL-23 by binding the p19 subunit and is FDA-approved for psoriasis.

Eligibility Criteria:
Inclusion Criteria:

* Diagnosis of PRP by clinical assessment
* Male age 18-99, willing to use a reliable form of birth control if sexually active with a woman who is able to become pregnant.
* Female age 18-99; either of non-childbearing potential or of childbearing potential who test negative for pregnancy and agree to use a reliable method of birth control or remain abstinent during the study and for at least 12 weeks following the last dose of guselkumab.
* Involved body surface area (BSA) ≥ 10% at baseline (moderate-to-severe disease).
* Are a candidate for phototherapy and/or systemic therapy.

Exclusion Criteria:

* Willingness to travel to Oregon Health and Science University (OHSU) for all study visits, or willing/able to participate in remote videoconferencing visits with access to a computer with internet and webcam capabilities.
* Known malignancy or lymphoproliferative disease (except treated basal cell skin cancer, treated squamous cell skin cancer, or treated cervical carcinoma in situ) for at least 5 years.
* Active, untreated, acute or chronic infection, or immunocompromised to an extent that such that participation in the study would pose an unacceptable risk to the subject.
* Positive for human immunodeficiency virus, hepatitis B virus, or hepatitis C virus.
* Have latent or active untreated tuberculosis (TB), a positive QuantiFERON-TB Gold test result, signs or symptoms of active TB on medical history or physical examination, or close contact with a person with active TB who have not undergone evaluation or treatment for TB. Those who are currently • Previous treatment with any agent that targets the interleukin 23 p19 subunit specifically.
* Systemic treatment with prednisone in the last 2 weeks, or other systemic therapies or phototherapy for PRP within the past 4 weeks or 5 half-lives prior to baseline, whichever is longer. For biologic therapies, the specific washout periods used will be: etanercept \<28 days; infliximab, adalimumab, i
* Have a known allergy or hypersensitivity to any biologic therapy that would pose an unacceptable risk to the subject if participating in this study.
* Have or intend to have a live vaccine within 3 months prior to baseline or 12 months prior to baseline in the case of the Bacillus Calmette-Guerin (BCG) vaccine, or any live vaccine during the course of study or within 3 months after the last administration of study drug.
* Had any major surgery within 8 weeks prior to baseline or will require major surgery during the study, that in the opinion of the investigator would pose an unacceptable risk to the subject.
* Presence of significant uncontrolled cerebrovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematologic, neurologic, or neuropsychiatric disorders, or abnormal laboratory screening values that, in the opinion of the investigator, pose an unacceptable risk to the subject if participating • Have clinical laboratory test results at screening that are outside the normal reference range of the population and are considered clinically significant, or have any of the following specific abnormalities: Neutrophil count \<1500 cells/μL, white blood cell count \<3500 cells/μL, platelet count \<100,000
* Women who are lactating or breastfeeding.
* Have any other condition that precludes the subject from following and completing the protocol, in the opinion of the investigator.
* Are investigator site personnel directly affiliated with this study and/or their immediate families (spouse, parent, child, or sibling).
* Are currently enrolled in, or discontinued from a clinical trial involving an investigational product or non-approved use of a drug or device within the last 4 weeks or a period of at least 5 half-lives of the last administration of the drug, whichever is longer, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study.