Comparative Efficacy and Safety of Topical Clobetasol Propionate 0.05% Ointment Versus Topical Methotrexate 1% Gel in Limited Plaque Psoriasis: A Prospective Open-Label Study

Background Psoriasis is a chronic, inflammatory, immune-mediated skin disorder characterized by abnormal keratinocyte proliferation and systemic inflammation. Limited plaque psoriasis, defined as involving less than a specified portion of the body surface area (BSA), presents as localized, erythematous, and scaly plaques. Though milder in extent, it significantly impairs quality of life due to physical discomfort and psychological distress. Topical therapies remain the primary treatment approach for this subtype. Potent topical corticosteroids, such as clobetasol propionate 0.05% ointment, offer rapid relief but pose long-term risks, like skin atrophy. In contrast, topical methotrexate 1% gel is emerging as a safer, sustained alternative. Objective The primary objective of this study was to compare the efficacy and safety of topical methotrexate 1% gel versus clobetasol propionate 0.05% ointment in patients with limited plaque psoriasis. Secondary objectives included the assessment of disease severity scores and adverse effects. Methods This prospective comparative, open-label study involved a per-protocol cohort of 70 patients. Patients were divided into two groups: clobetasol, 35 (50%) patients, and methotrexate, 35 (50%) patients, and were followed for 12 weeks. Results Clobetasol demonstrated faster initial clinical improvement by Week 4, but methotrexate yielded significantly better sustained results. By Week 12, 13 (37.1%) patients in the methotrexate group achieved Psoriasis Area and Severity Index (PASI)-75, compared to five (14.3%) in the clobetasol group (p = 0.026). Endline Physician's Global Assessment (PGA) scores showed seven (20%) methotrexate patients achieved clear skin, and 19 (54.3%) were almost clear, contrasting favorably against clobetasol (two (5.71%) clear; nine (25.7%) almost clear). Methotrexate significantly improved Beer Sheva Psoriasis Severity Score (BSPSS) values without serious adverse events. The clobetasol group reported atrophy in eight (22.9%) patients and tachyphylaxis in one (2.9%) patient at Week 10. Conclusion Topical methotrexate 1% gel is significantly superior to clobetasol propionate for sustained treatment. It provides high clinical efficacy and avoids steroid-associated adverse effects, making it a highly recommended, safer, long-term option for limited plaque psoriasis.