Apremilast for genital erosive lichen planus in women (the AP-GELP Study): study protocol for a randomised placebo-controlled clinical trial

Abstract

Background Genital erosive lichen planus (GELP) is a genital subtype of lichen planus, a chronic autoimmune inflammatory disease of unknown aetiology. In women, GELP is characterised by painful vulvo-vaginal mucosal erosions and scarring, often resulting in poor sexual health and reduced quality of life. Treatment options are limited and often with little effect. Apremilast, a phosphodiesterase 4-inhibitor, has been shown to have a positive effect on psoriasis and other inflammatory skin diseases. We aim to investigate the effect and safety of peroral apremilast in women with GELP in a randomised placebo-controlled double-blinded clinical trial. Methods We will recruit 42 adult women with characteristic clinical and/or histological features of moderate-to-severe GELP from a specialised vulva clinic in Oslo, Norway. The patients will be randomised 1:1 to either apremilast 30 mg BID (with an initial dose titration on days 1–6) or a placebo for 24 weeks. The concomitant use of topical corticosteroids will be allowed. The primary end point will be the mean GELP score, a clinical scoring system, at week 24 in the apremilast-treated patients versus the placebo-treated patients. The secondary end points will include the mean GELP score improvement from weeks 0 to 24, patient-reported use of topical steroids, the pain score on a visual analogue scale and the number of patients with GELP score improvements at weeks 16 and 24. The Physician Global Assessment , Patient Global Assessment and selected quality of life and sexual function assessments will be recorded at weeks 0, 16 and 24. The exploratory endpoints include description of immunohistochemical changes before and after apremilast therapy, assessed in vulvar or vaginal biopsies at weeks 0 and 24. Regular follow-ups for possible adverse events will be conducted. Discussion The study design is based on experience from studies on apremilast in other inflammatory skin diseases using equivalent apremilast doses for approved indications. The trial may provide evidence for the use of apremilast in women with this burdensome genital dermatosis. Trial registration ClinicalTrials.govNCT0365666. Registered on 4 September 2018.

Lichen Planus

“…Subsequently, a total of 5 LP patients, mostly with treatment-refractory disease, were reported to improve when treated with apremilast (203)(204)(205). Based on these reports, apremilast is currently evaluated in a randomized placebo-controlled clinical trial in women with genital erosive lichen planus (206). Currently, patients are recruited to this study (NCT03656666).…”

The efficacy and safety of deucravacitinib compared to methotrexate, in patients with vulvar lichen planus who have failed topical therapy with potent corticosteroids: a study protocol for a single-centre double-blinded randomised controlled trial

“…Nevertheless, we are optimistic that these challenges can be overcome in our RCT, which we are conducting in a dermato-gynaecology centre with a large patient base and a high referral rate. Most recently, Skullerud et al published the study protocol of their double-blinded RCT [ 20 ]. However, their study compared apremilast with placebo and not other systemic treatments.…”

Complex vulvar and vaginal disease in menopause

“…The trial is a randomized, placebo-controlled clinical trial based in Norway, lasting 24 weeks. A single open-label study in 2013 with 10 patients showed this treatment to be efficacious [17 ▪ ]. While it is difficult to perform large randomized, placebo-controlled trials on more rare disease states, hopefully, more studies will investigate more effective treatments for lichen planus.…”

“…The gold-standard treatment for lichen planus is topical high-potency corticosteroids like clobetasol propionate 0.05%. Second-line treatment options include calcineurin inhibitors like tacrolimus or even systemic immunosuppressants such as prednisolone, retinoids, methotrexate, cyclophosphamide, azathioprine, and mycophenolate mofetil [17 ▪ ]. Data for systemic treatment and robust clinical trials are indeed lacking and often only include small groups or case series [18].…”