Development of Predictive Psoriasis Response Endotypes Using Single Cell Transcriptomics

Psoriasis is a chronic systemic skin disease in which pro-inflammatory molecules contribute to the development of scaled inflamed skin and other disease-associated comorbidities such as increased risk of depression, heart attack, stroke, and metabolic syndrome. Some lesion-derived cytokines/chemokines are released into systemic circulation and increase lesional severity. Given their importance in the pathogenesis of psoriasis, the interleukins 12 (IL-12) and 23 (IL-23) are significant targets of biologic therapies.

Importantly, psoriasis patients exhibit variable responses to treatments targeting interleukins; one size does not fit all for these therapeutics. Our preliminary data demonstrates individual skin improvement (Responders) as well as lack of skin improvement (Non-Responders) in patients treated with monoclonal antibody therapy specifically targeting the shared (p40) subunit common to IL-12 and IL-23 (ustekinumab/Stelara). Interestingly, some Non-Responders to ustekinumab respond well to inhibition of the IL-23 pathway via the unique p19 subunit. We hypothesize that the pattern of differentially expressed genes (DEGs) among Responders and Non-Responders following anti-IL-12 and anti-IL-23 therapy may enable us to predict the likelihood of patient response to p40 antagonism as well as antagonism of the p19 subunit of IL-23. Single cell transcriptome analysis will be used to generate gene expression patterns that identify variable patient response patterns (endotypes).

Inclusion criteria

• Diagnosed with plaque-type psoriasis defined by either:

• A board-certified dermatologist, OR
• Dermatology Nurse Practitioner, OR
• Skin punch biopsy
• Insurance that includes an anti-p40 biologic (ustekinumab/.Stelara) and at least one anti-p19 biologic (guselkumab/Tremfya or risankizumab/Skyrizi)
• Must be naive to ustekinumab, guselkumab, and risankizumab.
• Involvement of body surface area (BSA) of at least 10% at screening and baseline visit.
• Able to give informed consent under IRB approval procedures

Exclusion criteria

• Pregnant, breastfeeding, or planning to get pregnant 8 weeks before, during, and 8 weeks after the study.
• Inability to provide informed consent
• Inability to secure ustekinumab and either gusekumab or risankizumab for use while on trial
• Use of tanning booths for at least 4 weeks prior to baseline visit
• Current or recent use of topical steroid, tar, phototherapy, Vitamin D, or retinoid therapy to target lesions for at least 2 weeks prior to baseline visit and for duration of trial
• Current or recent use of systemic or biologic therapy for at least 8 weeks prior to baseline visit
• Patients with psoriatic arthritis or other rheumatologic diseases (e.g., Crohn's disease).