Background: Methotrexate is a well-known standard therapy for psoriasis. The standard regimen is using six (2.5 mg) tablets/week that might be with many side effects. Objective: Finding a new regimen for oral methotrexate aiming to decrease side effects and increase its effectiveness. Patients and Methods: This therapeutic, comparative study done at the Center of Dermatology, Medical city, from October 2017 to October 2018. Fifty-three patients with moderate to severe psoriasis completed the study. They were divided into: Group (A) (27) patients were treated with the new oral regimen and Group (B) (26) patients were treated with the six tablets/week. Investigations including CBC, LFT and RFT were done. PASI score, BSA and side effects especially gastrointestinal ones were recorded. Results: They were 29 males and 24 females. Age ranged from 18 - 67 years. Disease duration ranged from 1 - 30 years. BSA involved ranged from 20% - 79%. The PASI score ranged from 10.2 - 45.7. After 8 weeks of treatment, there was statistically significant difference (p-value > 0.001) regarding PASI score and gastrointestinal side effects being less in Group (A). Group A patients were more satisfied. Conclusion: The new regimen used in the present study has lower gastrointestinal side effects and more efficacy.
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