Comparison of Efficacy and Safety of Deucravacitinib Versus Methotrexate in the Treatment of Moderate-to-Severe Plaque Psoriasis .

Background: Psoriasis is a chronic , immune-mediated inflammatory skin disorder affecting millions globally, the disease presents a major challenge to the physicians. When choosing a systemic therapy for moderate to severe plaque psoriasis, methotrexate is very good option, though its use is limited by its adverse effects. Several new treatments for psoriasis have appeared to be effective though they are not adequately investigated. Among them JAK inhibitors are leading clinical trials and can be a breakthrough in the treatment of psoriasis. Moreover, Very few studies have been performed to compare efficacy and safety of Deucravacitinib with Methotrexate therapy in the treatment of psoriasis. Objective: To assess Efficacy and Safety after commencement of therapy with Deucravacitinib and Methotrexate therapy in two different groups of patients with psoriasis. Materials and Methods: The study will be done on patients aged more than 18 years attending outpatient Department of Dermatology and Venereology department of Bangladesh Medical University. This will be a longitudinal study. It will be conducted in the Department of Dermatology and Venereology of Bangladesh Medical University for 12 months from the acceptance of the protocol. Patients of psoriasis with PASI (Psoriasis Area and Severity Index) score 12 or more will be the study population. A total number 106 patients with psoriasis of both sexes will be enrolled. They will be divided in group A (53 patients) and group B (53 patients) according to inclusion and exclusion criteria In group A, patients will be treated with Deucravacitinib 6mg once daily for 6 months and efficacy will be assessed by PASI (Psoriasis Area and Severity Index) score periodically. In Group B, patients will be treated with Methotrexate 10 mg once weekly at night after meal, with folic acid 5mg tablet the day after taking methotrexate and efficacy will be assessed using PASI scoring tool. Finally efficacy and safety of two treatment modalities will be compared. Statistical analysis will be done with Chi square test, Fisher's exact test and multivariate linear regression for intergroup comparison safety assessment will be done on the basis of clinical history, examination and laboratory finding at each follow up. Adverse events will be explained to the patients. Ethical clearance will be obtained from Institutional Review Board of Bangladesh Medical University. Ethical Consideration: The nature and purpose of the study will be informed in details to all the participants. Before obtaining the consent, patients will be explained about the purpose and duration of the study, detailed study procedure, the benefits and potential risks (if any) involved with the study. Relevant investigations and therapeutic treatment will be given free of cost. Informed written consent will be taken from every patient before enrolment. Each and every patient will enjoy their rights to participate, refuse or withdraw from the study at any point of the study. Patients not willing to be a part of the study or not fulfilling the inclusion criteria will not be included. Patients who will deny to continue taking part in study will be treated as before. The investigator will also have the right to collect information about health condition, treatment and laboratory reports. Expected Outcome: This study can help to compare efficacy and safety of Deucravacitinib with Methotrexate in treatment of moderate to severe plaque psoriasis. If Deucravacitinib proves to be superior to methotrexate therapy, patients will be benefited and treatment related adverse effects will be reduced.

Inclusion Criteria: * Adults ≥18 years of age with moderate-to-severe plaque psoriasis PASI score of at least 6 . * Patients with a history of prior therapy, including biologics were eligible for inclusion provided they completed the specified washout period (e.g., at least 12 weeks after the last dose of adalimumab) before randomization. (Bruce Strober, January 2023) Exclusion Criteria: For Deucravacitinib group (Group A) criteria: * Known hypersensitivity to Deucravacitinib. * Patients with active infection including HIV. * Clinically suspected or known case of tuberculosis. * Taking immunosuppressive drugs like Corticosteroids, Cyclosporine, Mycophenolate Mofetil. * Previous treatment with TYK2 inhibitors. * Presence of non-plaque forms of psoriasis (e.g., Guttate, Erythrodermic, Pustular). * Significant hepatic, renal, or hematologic abnormalities. * Pregnant or breastfeeding women(Chaplin 2023) For Methotrexate group (Group B) criteria: * Pregnant women and lactating mother. * Patients with active infection including HIV. * Impaired hepatic and renal functions. * Patients with Hb% \