The Efficacy and Safety of Deucravacitinib to that of Methotrexate, in Patients with Vulvar Lichen Planus who have Failed Topical Therapy with Potent Corticosteroids: A Randomized Controlled Trial

Vulvar lichen planus (VLP) is a chronic inflammatory dermatosis characterized by erythema, erosions and hyperkeratosis on the vulva with possible vaginal involvement. The condition is particularly difficult to treat and runs a chronic and progressive course, requiring long-term management and follow-up. The first-line treatment for VLP is potent topical corticosteroids. However, approximately 20-40% of patients require second-line treatment with systemic immunosuppression to control their disease. Some of the systemic medications that have been used to treat VLP include prednisolone, methotrexate, mycophenolate mofetil, azathioprine, hydroxychloroquine and cyclosporine, with varying results. The best documented agent appears to be methotrexate, with authors reporting moderate efficacy and safety profile. However, these studies were either retrospective or small case series. Overall, there is a lack of high-quality evidence, such as randomized controlled trials (RCTs), to compare and guide second-line systemic treatments in VLP. The pathogenesis of VLP is not completely understood, but there is evidence of involvement of tyrosine kinase 2 (TYK2) mediated pathway. One drug known to modulate the TYK-2 pathway is Deucravacitinib (BMS-986165), a novel, oral, selective TYK-2 inhibitor. It is being studied in patients with psoriasis, psoriatic arthritis, and systemic lupus erythematosus with promising results. Given the lack of high-quality evidence to guide the use of second-line systemic treatments in VLP, the evidence of involvement of TYK2-mediated pathway, and that the best documented systemic agent in VLP to date is methotrexate, the aim of this study is to conduct a double-blinded RCT comparing the efficacy and safety of Deucravacitinib to that of Methotrexate, in patients with VLP who have failed first-line treatment with potent topical corticosteroids. Hypothesis: Deucravacitinib will be superior to methotrexate in treating VLP patients who have failed topical therapy with potent corticosteroids.