The Power of Two: Effective Management of Severe Refractory Psoriasis Through Combined TYK2 and IL-23 Inhibition

This case report highlights the clinical course of a 76-year-old male with severe, treatment-refractory psoriasis that was unresponsive to many topical and systemic therapies over many years. Prior treatments included topical corticosteroids, oral prednisone, and systemic immunosuppressants such as methotrexate, cyclosporine, and mycophenolate, all of which provided minimal or transient benefit. Biologic therapies including dupilumab, ixekizumab, and apremilast similarly did not achieve sustained disease control. Narrowband UVB phototherapy offered some temporary resolution, however symptoms promptly returned upon cessation. The patient eventually achieved significant clinical improvement with a novel combination therapy of risankizumab, an IL-23 inhibitor, and deucravacitinib, a selective TYK2 inhibitor. Initiation of risankizumab monotherapy resulted in partial improvement, reducing body surface area (BSA) involvement from 65% to 20%. Given the incomplete response and history of refractory disease, deucravacitinib was then added, leading to further improvement and BSA involvement decreasing to 4% over this time period. The combination was well tolerated, with no adverse effects reported. This case underscores the complexity of managing psoriasis in patients with recalcitrant disease. It also suggests the potential efficacy and safety of combining targeted biologic and oral therapies in patients who fail to respond adequately to monotherapy. The success of this dual approach may reflect complementary mechanisms of action and highlights the need for individualized, flexible treatment strategies in difficult-to-treat psoriasis cases. Further studies are warranted to evaluate the long-term efficacy and safety of this combination in broader patient populations.