Guselkumab in the Treatment of Adults With Pyoderma Gangrenosum (PG)

Inclusion Criteria: * Willingness to comply with study procedures/requirements * Capable of giving informed consent * Diagnosis of at least one PG ulcer by clinical, histological and laboratory assessments with a minimum wound size of 4 cm2. * Undergoing at least once a week standard of care wound care at home or at a wound care facility * Are candidate for systemic therapy. Must be on a stable dose of prednisone of 20 mg/day for at least two weeks prior to first drug administration. * Males ages 18-99 who agree to not father a child or donate sperm while on study and at least 12 weeks following last dose of the study drug. If subject is sexually active male and could cause pregnancy, subject much be sure that female partner(s) are using birth control that works well or not have sex. * Females ages 18-99; either of non-childbearing potential or of childbearing potential who test negative for pregnancy and agree to use at least two reliable methods of birth control or remain abstinent during the study for at least 12 weeks following the last dose of guselkumab. * Willingness to travel to study site for all study visits or living \>30 miles from study site and willing/able to participate in remote videoconferencing visits with access to a computer with internet and webcam capabilities. * Be willing to undergo perilesional and non-lesional skin biopsy at week 0 and week 32 resulting in 4 biopsies during the course of the study. Participants can choose if they are willing to provide 2 additional biopsies at week 16. Refusal to give consent for any of the optional research samples does not exclude participant from participation in the study. Exclusion Criteria: * Has previously received at any time any therapeutic agent directly targeted to IL-23 including, but not limited to, guselkumab, risankizumab, tildrakuzumab, or mirikizumab * Any drug treatment specifically for PG including but not limited to biologics (or biosimilar of), experimental antibodies, small molecules and oral immunosuppressives used within washout periods specified below, prior to first dose of study drug: 1. 12 weeks for ustekinumab, ixekizumab, secukinumab, brodalumab; 2. 8 weeks for infliximab; 3. 6 weeks for adalimumab; 4. 4 weeks for cyclosporine A, etanercept, inhibitors of the JAK/TYK pathway and PD4 inhibitors; 5. 2 weeks for Calcineurin inhibitor topicals (including but not limited to pimecrolimus and tacrolimus) and other advanced topicals (including but not limited to roflumilast and tapinarof). If not specified specifically, a time of 4 weeks or 5 half-lives of the drug (whichever is longer) prior to first drug administration. * Intralesional corticosteroids within 4 weeks of screening. * Active clinically infected ulcers. Individuals will be eligible for enrollment following completed treatment and resolution of infection. Antibiotics for wound superinfection are allowed. * Immunomodulating medications for managing underlying comorbidities associated with PG, but not PG itself (e.g., for irritable bowel disease (IBD) or rheumatoid arthritis), are allowed as combination therapy except for Methotrexate (MTX) and Leflunomide which are allowed individually but not in combination. * Concurrent skin disease that is deemed to interfere with assessment of ulcer. * Have signs or symptoms suggestive of possible lymphoproliferative disease, including lymphadenopathy or splenomegaly or a history of lymphoproliferative disease within 5 years before screening; or currently has a known malignancy or has a history of malignancy within 5 years before screening, with the exception of a nonmelanoma skin cancer that has been adequately treated with no evidence of recurrence for at least 3 months before the first study drug administration or cervical carcinoma in situ that has been treated with no evidence of recurrence for at least 3 months before the first study drug administration. * Recent (within past 6 months) cerebrovascular accident, myocardial infarction, coronary stenting. Uncontrolled hypertension - confirmed systolic blood pressure \>160 mmHg or diastolic blood pressure \>100 mm Hg. * Clinically significant (per investigator's judgement) drug or alcohol abuse within the last 6 months preceding the Baseline Visit. * Has not fully recovered from major surgery (e.g., requiring general anesthesia and hospitalization) within 8 weeks before screening, or has such surgery planned during the time the participant is expected to participate in the study (40 weeks) which in the opinion of the investigator would pose an unacceptable risk to the subject. * Presence of significant uncontrolled respiratory, hepatic, renal, 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 in the study or of interfering with the interpretation of the data. * 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, Lymphocyte count \<500 cells/µL, Platelet count \<100,000 cells/µL, AST or ALT or alkaline phosphatase \> 2 times the upper limit of normal, Hemoglobin \<10 g/dL, Serum creatinine ≥1.5 mg/dL (SI: ≤137 μmol/L), White blood cells \<3500 cells/ µL * Participant has known allergies, hypersensitivity, or intolerance to guselkumab or its excipients. * Individuals who are pregnant, lactating or breastfeeding. * History of chronic or recurrent infections, or active, untreated, acute infection, or immunocompromised to an extent that participation in the study would pose an unacceptable risk to the subject based on the investigator's clinical assessment. * Clinically serious infection or received intravenous antibiotics for an infection, within 8 weeks before first dose. * Have signs or symptoms suggestive of active Tuberculosis (TB) upon medical history and/or physical examination. An exception is made for participants who are currently receiving treatment or will initiate treatment for latent TB prior to first administration of study intervention. For participants with a history of treated latent TB there must be documentation of appropriate treatment prior to the first administration of study intervention. * Positive for human immunodeficiency virus (HIV), active hepatitis B virus, or hepatitis C virus. A positive Hepatitis B surface antibody test with a corresponding negative hepatitis B surface antigen test indicates immunity to the disease and will not be exclusionary. * Symptomatic herpes zoster infection within 12 weeks of screening or recurrent or disseminated (even a single episode) herpes zoster. * Symptomatic herpes simplex or disseminated (even a single episode) herpes simplex at the Week 0 (baseline) visit. * History of disseminated opportunistic infections (e.g., listeriosis and histoplasmosis). * Have received a live vaccine within 12 weeks prior to baseline or intend to have a live vaccine during the course of the study or 4 weeks after last study drug administration or 12 weeks after last study drug administration for Bacillus Calmette-Guérin (BCG) vaccine. * 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.