Comparison of ALitretinoin with PUVA as the first line treatment in patients with severe chronic HAnd eczema (ALPHA trial)

Hand eczema (HE) is one of the most common skin disorders and an important cause for morbidity and occupational disability. HE is a heterogeneous disease which presents with various subtypes. The impact on daily life of sufferers is considerable. The 1-year prevalence of HE is estimated to be up to 10% in the general population. The proportion of patients who develop severe chronic HE (CHE) is estimated to be 5-7% of all patients with HE. HE therapy is delivered in escalating steps. When patient education, allergen/irritant avoidance and topical treatment are not sufficient to control the disease, UV therapy or systemic immune-modifying drugs are used. Alitretinoin (AL) is licensed for severe, CHE unresponsive to treatment with potent topical corticosteroids. However, currently available clinical evidence for the treatment of CHE is not compelling enough to guide clinical practice. The lack of clear evidence based data has been outlined by different national and international expert groups. Given the high socioeconomic impact of the disease there is a pressing need for comparative studies on available first line treatments, and on long-term outcome of currently used therapies. The NIHR has recognised this need and launched this commissioned call aiming to compare AL to other treatment options. Our choice of comparator for AL was based on published clinical trials, on feedback from UK dermatologists, patients and the UK Dermatology Clinical Trials Network (UKDCTN). As research and audit data on treatment choices for CHE are unavailable, we performed a survey among 194 UK dermatologists; the most frequent first choice approaches for CHE were PUVA, oral steroids and AL. When asked which strategy was thought to be most efficient for long-term outcome 20% of clinicians indicated that they did not know whilst 43% of clinicians opted for AL and 30% PUVA. Therefore, we propose a multicentre, open, prospective, two-arm parallel group, adaptive, randomised controlled trial comparing the response to the currently most common first line therapies in UK clinical practice, PUVA and AL. In line with daily clinical practice (survey results) topical steroids and moisturisers will be applied along with the intervention. Frequent assessments will be performed for 52 weeks post randomisation (24 weeks for participants randomised from 1st October 2019). The primary outcome measure will be at 12 weeks to directly compare short term response to first line treatments (and allow comparison to existing trials). Key secondary outcomes include long term outcome with focus on remission period, patient’s benefit, quality of life (QoL) and cost effectiveness outcomes including resource costs associated with patient treatment, monitoring, and productivity costs. The physician’s global assessment (PGA) will direct treatment pathways after randomisation. Patients with insufficient response to PUVA or AL will be treated according to usual clinical practice which may include switching to the alternative intervention, or immunosuppressants such as methotrexate or cyclosporine A. This will provide valuable pilot data on second line therapeutic approaches and will be useful in informing the choice of therapies in future trials. An emphasis of this study will be on eczema subgroups, patient education and patient-relevant benefits. A sub-study on molecular parameters linked to distinct eczema subgroups will give additional information on subgroup specific treatment responses.