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This combination therapy involves the systemic administration of etanercept, a recombinant human TNF-receptor fusion protein, alongside the topical application of tacrolimus, a small molecule calcineurin inhibitor. Developed as an investigator-initiated study by the University of Medicine and Dentistry of New Jersey (now Rutgers University), the regimen was evaluated for the treatment of moderate to severe psoriasis. Etanercept works by binding to and neutralizing tumor necrosis factor-alpha (TNF-α), a key pro-inflammatory cytokine in psoriasis pathogenesis. Tacrolimus, applied topically as a 0.1% ointment, inhibits T-lymphocyte activation by binding to the intracellular protein FKBP-12 and subsequently inhibiting calcineurin, thereby reducing local inflammation. The combination was studied in a Phase 2 split-body trial to determine if adjunctive topical therapy could enhance the efficacy of systemic biologic treatment in patients who are candidates for or poor responders to etanercept monotherapy.
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