Laser vs Clobetasol for Lichen Sclerosus

Study Overview
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Brief Summary
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Lichen sclerosus (LS) is a common autoimmune disease of the genital skin. It affects 1/900 women with an age peak in the sixth decade of life and is manifested by chronic inflammation of the genital, perineal, and perianal areas associated with itching, burning, pain, and soreness. In addition, LS is associated with an increased risk of vulvar cancer. Treatment options for LS include topical steroids such as clobetasol, immunomodulators such as tacrolimus, and non-ablative laser treatment. Although both treatments are well documented and used in clinical practice, direct comparative studies of the efficacy of topical corticosteroids versus laser treatment in women with LS are rare. For example, a PubMed literature search (search date 2021-03-14; search terms: lichen sclerosus, laser, corticosteroids, steroids, clobetasol, randomized) identified only a single randomized trial with limited power. Given the available evidence, further high-quality studies are needed to define the superiority/inferiority of the different available treatment options such as nonablative lasers and topical corticosteroids. Therefore, in this prospective, randomized, open-label, comparative study, treatment success after 3 courses of non-ablative treatment with CO2 laser every 14 days will be compared with treatment success after topical application of clobetasol 0.05% over 3 months (daily in the first month, every other day in month 2, and 3 times/week during month 3) at the time point 3 months after treatment initiation.

Detailed Description
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Lichen sclerosus (LS) is a common autoimmune disorder of the genital skin. It affects 1/900 women with an age peak in the sixth decade of life. LS is a chronic inflammatory condition affecting the genital, perineal, and perianal areas and causes itching, burning, pain, and soreness. Histologically, LS is characterized by epidermal atrophy, hyperkeratosis, follicular plugging, degeneration of the basal layer, and subepidermal hyalinization of collagen in the papillary dermis with a lymphocytic infiltrate. Affected women typically suffer significant long-term genital damage including scarring, fusion of the vulval labia, narrowing of the vaginal opening, dyspareunia, and burying of the clitoris. In addition, LS is associated with an increased risk of vulvar cancer. Treatment options of LS include topical steroids such as clobetasol, topical immunomodulators such as tacrolimus, and non-ablative laser treatment. In a systematic review of the literature with 7 studies and 249 participants, clobetasol achieved improvement rates and remission rates of 70% to 89% and 20% to 35%, respectively. In comparison, non-ablative laser treatment leads to significant improvements in vulvar itching, dryness, pain, and dyspareunia in 50% to 85% of women with remission rates of up to 80% after 14 years of follow-up. Although both treatments are well documented and used in clinical practice, direct comparative studies assessing the efficacy of topical corticosteroids versus laser treatment in women with LS are rare. For example, in a PubMed literature search (search date 2021-03-14; search terms: lichen sclerosus, laser, corticosteroids, steroids, clobetasol, randomized) only one randomized trial was identified. In this study, the authors included 40 women with LS and compared 3 applications of non-ablative laser 2 weeks apart with 4 weeks of twice daily (2 weeks), once daily (1 week), and every other day (1 week) of topical clobetasol 0.05% cream. After 3 months of treatment laser-treated women had a significantly higher sum score (including burning, itching, and pain) measured on an 11-step visual analogue scale (VAS). Both treatments demonstrated histological improvement with reductions of inflammatory hallmarks in skin biopsies. Given this body of evidence, more high-quality studies are needed to define the superiority/inferiority of the different available treatment options such as non-ablative laser and topical corticosteroids. Therefore, a prospective, randomized trial comparing non-ablative CO2 laser treatment and topical clobetasol 0.05% will be conducted. The aim of this prospective, randomized, open-label, comparative trial is to establish or refute the superiority of 3 courses of non-ablative treatment by CO2 laser every 14 days compared to topical clobetasol 0.05% (daily in month 1, every other day in month 2, and 3 times/week in month 3) for 3 months. The primary endpoint of this study is a sum score including the pathognomonic symptoms of LS, namely vulvar burning, itching, and pain, each measured on an 11-step VAS. Secondary endpoints will include the physician-scored rate of visual improvement (measured on an 11-item VAS), side effects, and patient-reported outcomes such as subjective overall improvement, general satisfaction, and quality of life (measured by a validated questionnaire for vulval disorders; i.e. the VDQI (Vulval Disease Quality of Life Index).

Official Title
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CO2 Non-ablative Laser Versus Topical Clobetasol for Lichen Sclerosus: a Prospective, Open-label, Randomized Trial

Conditions
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Lichen Sclerosus

Intervention / Treatment
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* Drug: Clobetasol 0.05% Emollient Top Cream
* Device: Non-ablative CO2 Laser


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women, age ≥ 18 years Established diagnosis of LS (vulva and/or perineum and/or perianal region) Willingness to comply with study requirements No significant language barrier Exclusion Criteria: Concurrent immunosuppressive treatment A history of vulvar cancer and/or vulvar dysplasia A history of vulvar surgery A contraindication against clobetasol treatment A known sun light allergy A known skin condition interfering with local ablative treatment such as neurodermatitis or bullous pemphigoid

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Prospective randomized open single center study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Clobetasol Group<br>Treatment with clobetasol-0,05% over 3 months (month 1: daily, month 2: every other day, month 3: 3x per week) | Drug: Clobetasol 0.05% Emollient Top Cream<br>* Topical corticosteroid treatment of affected vulvar skin areas.<br>* Other names: Dermoxin (Germany), Temovate, Clobex, Dermovate, Impoyz;|
| Experimental: Laser Group<br>3 applications every 14 days of a non-ablative CO2 laser treatment | Device: Non-ablative CO2 Laser<br>* Superficial non-ablative laser treatment of affected vulvar skin areas.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vulvar burning, itching, and pain | Summary score of three symptoms of LS, i.e. vulvar burning, itching, and pain (11-item VAS each). Higher values mean worse outcome. | from date of randomization until 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy - Physician-scored rate of visual improvement (0-10) | 11-item VAS; higher values mean better outcome. | 3 months after treatment start | 
| Safety - Number and severity of side effects | Side effects (perioperative and postoperative complications up to 7 days) including but not limited to bleeding, infection, wound breakdown, unscheduled re-admission, and local pain necessitating systemic analgesia. | 0-7 days after laser treatment (laser group); as well as throughout study duration (3 months; both groups) | 
| Subjective overall improvement (0-10) | The patient's subjective judgement of improvement (11-item VAS); higher values mean better outcome. | 3 months after treatment start | 
| Vulval Disease Quality of life Index (0-45) | Quality of life assessed before the start of therapy, after every treatment course (laser group; days 0, 14, 28, 42) or after 2 and 6 weeks (clobetasol group; days 0, 14, 42), and after 3 months (both groups) using a standardized, validated questionnaire (VDQI, Vulval Disease Quality of life Index). Lower score mean better outcome. | Throughout study completion (3 months; for a total of 4 or 5 assessments, depending on group assignment) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Corticosteroids, Lichen Sclerosus, Laser, Clobetasol