Methotrexate treatment 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

This trial will try methotrexate to reduce symptoms and prevent further scarring in women with severe vulvar lichen sclerosus who have not improved with high‑potency topical steroids.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 12 (estimated)
• Ages: 18 Years and up
• Sex: Female
• Sponsor: Clinica Dermatologica Arbache ltda (Academic / other)
• Drugs / interventions: Methotrexate
• Locations: 1 site (São José dos Campos, São Paulo)
• Trial ID: NCT07352917 on ClinicalTrials.gov

What this trial studies

This is a prospective, open‑label Phase 2 interventional study testing methotrexate in patients with severe vulvar lichen sclerosus. Eligible participants must have histopathological confirmation, a Vulvar Quality of Life Index (VQLI) score above 24, and persistent disease after at least three months of high‑potency topical corticosteroids. Baseline labs (CBC, liver and kidney function, and viral serologies) must be normal and women of childbearing potential require a negative pregnancy test. Clinical response will be tracked over time using a standardized clinical scoring system for vulvar lichen sclerosus.

Who should consider this trial

Good fit: Women with histologically confirmed genital lichen sclerosus, a VQLI score >24, persistent symptoms or progressive deformity after ≥3 months of high‑potency topical corticosteroids, normal baseline labs, and (if applicable) a negative pregnancy test.

Not a fit: Patients with mild disease controlled by topical steroids, contraindications to methotrexate (for example significant liver or kidney disease, active infections, or pregnancy), or inability to comply with clinic visits and monitoring are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, methotrexate could reduce symptoms, slow or prevent further vulvar scarring, and improve sexual function and overall quality of life.

How similar studies have performed: Small case series and retrospective reports have suggested benefit of methotrexate for refractory vulvar lichen sclerosus, but prospective controlled data are scarce.

Eligibility criteria

Inclusion Criteria:

* 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 Criteria (assessed before signing the Informed Consent Form):

* 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.

Exclusion Criteria (assessed after signing the Informed Consent Form):

* 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.

Where this trial is running

São José dos Campos, São Paulo

• DermoCentro — São José dos Campos, São Paulo, Brazil (Recruiting)

Study contacts

• Study coordinator: Samir Arbache, Phd

Conditions Vulvar Lichen Sclerosus; Vulvar lichen sclerosus; Quality of life; methotrexate