efficacy of guselkumab in treating hailey hailey disease

Conditions: Hailey Hailey Disease

Summary: hailey-hailey disease (hhd) is a debilitating genetic skin disorder, affecting mainly body folds with erythema and painful erosions and blisters. histopathological findings include epidermal hyperplasia, suprabasilar clefting, dyskeratosis and acantholysis of keratinocytes. a final diagnosis of hhd is usually confirmed based on clinical and histopathological findings in line with genetic testing. several treatment options have been proposed for this chronic and disabling disorder, however, there is no reproducibly effective therapeutic for it. the primary objective is to evaluate the treatment response of guselkumab. single-center, non-randomized, single-arm, open-label, phase ii trial to evaluate the efficacy and safety of guselkumab for the treatment of patients with hhd.

several treatment options have been proposed for hhd as chronic and disabling disorder, however, there is no reproducibly effective therapeutic for it. the primary objective is to evaluate the treatment response of guselkumab. after the participant has been deemed an appropriate candidate for the study and has signed the consent form, they will be enrolled. all participants will be started on guselkumab 100mg at the fda-approved psoriasis dose and will be seen for clinical follow-up 4, 12, 24 weeks after initiation of therapy. a 12-week follow-up period will be conducted post-administration of the final dose of guselkumab to monitor safety. laboratory monitoring including complete blood count, basic metabolic panel, liver function tests, and pregnancy test (if applicable) will also be performed at 1 month, 3 months, and 6 months after starting therapy. at each visit except week 20 a full h\&p, complete review of systems and physical examination will be performed. outcomes will be assessed and full-body photography will be performed at each visit except week 20. research tissue samples (skin biopsies) will be obtained at baseline (prior to therapy) after 24 weeks of treatment in all participants. research blood will be obtained at screening, baseline and after 4, 12, and 24 weeks of guselkumab therapy.

Eligibility criteria:
inclusion criteria: * a documented diagnosis of hailey-hailey disease confirmed with clinical, and histopathologic findings * disease affecting more than one body site with at least moderate severity * if patients are taking other systemic therapies for their hhd (antibiotics, prednisone), they must be taking a stable dose of the other medication(s) for at least 3 months with no plans to change the regimen in the next 6 months. with the exception of antibiotics, methotrexate or low dose prednisone (less than 5 mg daily), use of concomitant immunosuppressants, e.g. azathioprine, etc. and biologics other than tnf-α inhibitors will not be permitted. * patients must be willing to have skin biopsies, blood collection, and total body photography and to comply with clinic visits exclusion criteria: * patients with a history of malignancy (except history of successfully treated basal cell or squamous cell carcinoma of the skin over six months prior to first study drug administration). * patients known to be hiv or hepatitis b or c positive. * patients planning to receive live vaccines during the duration of the study. * patients with a positive tuberculin skin test or positive quantiferon tb test. * patients with significant hepatic impairment (child-pugh class b and c). * patients taking immunosuppressive and biologic medications, except for methotrexate, low-dose prednisone, and tnf-α inhibitors, including but not limited to mycophenolate mofetil, azathioprine, tacrolimus, and cyclosporine. * are pregnant, nursing, or planning a pregnancy while enrolled in the study or for 12 weeks after the study agent injection for women or are planning to father a child while enrolled in the study or for 12 weeks after the last study agent injection. * prior biologic use within the last 3 months. * participant has known allergies, hypersensitivity, or intolerance to guselkumab or its excipients (refer to investigator's brochure) * 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. * 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. * 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. * patients with the potential for keloid formation, e.g. patients with a propensity for keloid formation, defined as a personal history of 3 or more keloids.