Proactive against reactive therapy for the prevention of lichen sclerosus exacerbation and progression of disease – a pragmatic, parallel group randomised controlled trial with embedded economic evaluation and process evaluation (PEARLS).
Every two weeks, women and girls with a chronic skin condition called lichen sclerosus could prevent painful flares and reduce their risk of vulval cancer by applying a steroid cream—even when they feel fine. Lichen sclerosus affects the genital skin, causing itching, scarring, and a small but real risk of cancer. Standard treatment clears symptoms in about 70% of patients, but doctors do not know whether patients should keep using the cream twice a week long-term (proactive therapy) or only when symptoms return (reactive therapy). This trial will settle that question. Over 57 months, the researchers will recruit 5-year-olds and adults with controlled lichen sclerosus from NHS hospitals. Half will use a potent steroid cream twice weekly regardless of symptoms; the other half will use it only during flares. The team will track how many flares each group has over a year, whether scarring worsens over two years, and whether proactive treatment prevents vulval cancer. They will also measure quality of life, sexual function, side effects, and cost-effectiveness. If proactive therapy wins, it could become a simple, low-cost way to keep patients symptom-free, slow disease progression, and cut cancer risk. If not, patients and clinicians will have clear evidence to choose the approach that suits them.
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RESEARCH QUESTION: In people 5+years with controlled vulval lichen sclerosus (LS), is maintenance treatment with topical corticosteroid (TCS) twice weekly (‘proactive therapy’) better than as required treatment (‘reactive therapy’) for reducing number of flares over 12 months? BACKGROUND: LS is a chronic inflammatory condition that mainly affects female genital skin. It causes distressing symptoms that impact on daily living/quality of life (QOL) as well as causing progressive anatomical changes and a risk of cancer. First-line treatment with superpotent TCS brings LS into remission in around 70% of women and girls. However, it is unclear whether long term, proactive maintenance treatment (using TCS twice weekly even if no symptoms) is better than reactive treatment (only using TCS during flares) to minimise flares and stop disease progression AIMS AND OBJECTIVES: To assess proactive versus reactive use of TCS 1)effectiveness over 12 months in reducing flares; 2)effectiveness over 24 months in reducing disease progression; 3)TCS safety over 24 months; 3)cost effectiveness; 4)to understand acceptability, barriers and facilitators to using prescribed treatment regimens DESIGN: 2-arm, parallel-group, randomised, unblinded, multicentre, superiority trial PARTICIPANTS: People 5+ years; controlled vulval LS; clinical or biopsy proven diagnosis; recruitment and follow up in secondary care INTERVENTION: Potent or superpotent TCS used two non-consecutive days per week even in absence of symptoms (‘proactive treatment’) CONTROL: Treat flare as required with potent or superpotent TCS (‘reactive treatment’) daily until resolution (typically up to 7 days) PRIMARY OUTCOME: Number of flares over 12 months. A flare is defined as increase in symptoms/clinical signs leading to use of rescue TCS SECONDARY OUTCOMES: Cumulative incidence of worsening of scarring using Vulvar Architectural Severity Scale at 12/24 months by blinded assessor (adults only); time to first flare; clinician global assessment at 3/6/12/18/24 months; adverse events of TCS e.g.stinging, skin thinning; condition-specific QOL at 3/6/12/18/24 months using Vulvar Quality Life Index (adults), Children’s Dermatology Life Quality Index, ; sexual function using Female Sexual Function Index (adults only); treatment acceptability; generic utility instrument to measure QOL using EQ-5D (teens and adults) or CHU-9D (children) at 3/6/12/18/24 months; development of vulval intraepithelial neoplasia/vulval squamous cell carcinoma captured from routine clinical data TIMELINE: The project will run for 57 months IMPACT AND DISSEMINATION: The study will inform the long term treatment of LS. If evidence of superiority for proactive therapy is found, this will lead to a reduction of flares (thereby improving QOL) and possibly minimise disease progression and reduce cancer development. An important safety message about TCS use in vulval skin will be conveyed to patients and patient groups. Strategies to encourage patients to adhere to long term treatment will be developed through in-depth qualitative work. If proactive therapy is not found to be superior, patients and clinicians can make an informed choice as to which strategy is preferred for the individual. We will disseminate our findings via scientific papers/conferences, patient groups, stakeholder dissemination events, social and conventional media, and other stakeholder engagement
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