Methotrexate for Severe Vulvar Lichen Sclerosus
A Prospective Phase II Open-Label Pilot Study Evaluating the Efficacy and Safety of Methotrexate in the Treatment of Severe Vulvar Lichen Sclerosus
Clinica Dermatologica Arbache ltda
12 participants
Jan 21, 2026
INTERVENTIONAL
Summary
Vulvar lichen sclerosus is a chronic inflammatory skin disease affecting the vulva and genital region, which may cause intense pruritus, pain, burning sensations, and progressive scarring. In severe cases, the disease may lead to significant anatomical changes, sexual dysfunction, and a reduction in quality of life. First-line treatment for vulvar lichen sclerosus consists of high-potency topical corticosteroids. Although many patients experience symptom relief, a considerable number of women continue to have persistent symptoms or progressive anatomical damage. For these patients, therapeutic options are limited. MTX is an immunomodulatory medication that has been used for several decades in the treatment of inflammatory and autoimmune diseases. Previous clinical observations suggest that MTX may be beneficial for patients with severe or treatment-resistant vulvar lichen sclerosus; however, prospective clinical studies in this population remain scarce. This prospective, open-label, phase II pilot study aims to evaluate the efficacy and safety of subcutaneous injectable MTX, administered once weekly at a standardized initial dose of 12.5 mg, in women with severe vulvar lichen sclerosus who have not responded adequately to standard topical therapy. Participants will receive treatment for 12 months, with regular clinical and laboratory monitoring. The primary objective of the study is to assess whether treatment with MTX leads to improvement in symptoms and stabilization of vulvar skin changes, using patient-reported outcome measures and standardized clinical assessments. Secondary objectives include evaluation of treatment tolerability, adherence, and the occurrence of adverse events. As a pilot study, this research is designed to generate preliminary data on feasibility, safety, and potential clinical benefit, which may guide future larger controlled studies and contribute to the development of evidence-based therapeutic strategies for women with severe vulvar lichen sclerosus.
Eligibility
Inclusion Criteria6
- Clinical diagnosis of genital lichen sclerosus et atrophicus (vulvar, perineal, or perianal);
- Histopathological diagnosis of genital lichen sclerosus et atrophicus;
- Disease severity defined according with a score above 24 on the Vulvar Quality of Life Index (VQLI);
- Failure of symptom regression or progressive genital deformity after at least 3 months of treatment with a high-potency topical corticosteroid;
- Normal baseline laboratory evaluation, including complete blood count, liver and kidney function tests, and negative serologies for HIV and hepatitis B and C;
- For women of childbearing potential, a negative pregnancy test at screening.
Exclusion Criteria16
- Lack of full mental or psychiatric capacity;
- Need for assistance from a third party (legal guardian) to participate in the study;
- Significant difficulty in understanding or expressing oneself in Portuguese;
- Unavailability or inability to complete Likert-scale questionnaires;
- Inability to comply with study requirements, including adherence to the treatment schedule and attendance at follow-up visits;
- Unrealistic expectations regarding treatment benefits or the possibility of adverse effects;
- Intention to become pregnant during the study period;
- Refusal to adopt at least one adequate contraceptive method (hormonal or barrier) in women of childbearing potential;
- Poor adherence to the commitment to abstain from alcoholic beverages;
- Uncontrolled autoimmune comorbidities;
- Refusal to sign the Informed Consent Form after adequate explanation and clarification of doubts;
- Any indication of inability to comply with the conditions established in the research protocol. Decisions will be made to ensure participant safety and study integrity, with appropriate communication regarding the reasons for exclusion.
- Elevation of liver enzymes above normal limits or impaired renal function during laboratory monitoring. Exclusion refers to discontinuation of the experimental intervention; however, the participant will continue to receive comprehensive medical follow-up as needed;
- Pregnancy. The participant will be withdrawn from the study intervention and referred for obstetric care, while continuing to receive medical follow-up;
- Lack of cooperation, failure to attend scheduled follow-up visits, or failure to undergo required laboratory monitoring;
- Any other condition that limits the participant's ability to comply with study procedures, as determined by the responsible investigator.
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Interventions
Subcutaneous injectable methotrexate administered once weekly, starting at a standardized initial dose of 12.5 mg per administration. Dose adjustments may be performed according to clinical response and safety monitoring, based on predefined protocol criteria. Folic acid supplementation will be administered on the day following the weekly methotrexate injection.
Locations(1)
View Full Details on ClinicalTrials.gov
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NCT07352917