Study protocol: efficacy of oral alitretinoin versus oral cyclosporine A in patients with severe recurrent vesicular hand eczema (ALICsA): a randomised prospective open-label trial with blinded outcome assessment

Abstract

IntroductionSystemic treatment with alitretinoin is registered for all clinical types of severe chronic hand eczema. However, it is especially effective in the hyperkeratotic subtype and less effective in non-hyperkeratotic forms. Cyclosporine A (cyclosporine) is prescribed for hand eczema in daily practice as well. It has shown to be particularly effective in patients with vesicular hand eczema. The primary objective of this study is to compare efficacy of alitretinoin and cyclosporine in the treatment of severe recurrent vesicular hand eczema.Methods and analysisThis is an investigator-initiated randomised prospective open-label trial with blinded outcome assessment. Severity assessments and laboratory measurements will be conducted corresponding to daily practice. The study population will consist of 72 adult patients (age 18–75 years) with severe recurrent vesicular hand eczema. Patients are treated with either (group I) alitretinoin 30 mg once daily or (group II) cyclosporine with a starting dose of 5 mg/kg/day and a decrease in dosage after 8 weeks to 3–3.5 mg/kg/day. The treatment period is 24 weeks for both drugs. Primary endpoint for efficacy is response to treatment, defined as an improvement of ≥2 steps on a Physician Global Assessment, using a validated Photoguide, after 24 weeks of treatment. Secondary endpoints are improvement of Hand Eczema Severity Index, Quality of Life in Hand Eczema Questionnaire and a Patient Global Assessment. Adverse events and time to response will be registered. Furthermore, cost-utility, quality-adjusted life years and cost-effectiveness will be assessed with the EQ-5D-5L questionnaire while monitoring costs.Ethics and disseminationThis protocol was reviewed and approved by the Medical Ethical Review Board of the University Medical Centre Groningen (reference METc 2015/375). The study will be conducted according to the principles of the Declaration of Helsinki, in accordance with the Dutch Medical Research Involving Human Subjects Act.Trial registration numberNCT03026946; Pre-results.

Responsiveness and interpretability of the Hand Eczema Severity Index

“…However, one should keep in mind that the MIC corresponding to a one‐step improvement on the Photoguide is probably not always a sufficient clinical improvement when comparing treatments . Various studies in hand eczema have defined ‘response to treatment’ as an improvement of at least two steps or achieving ‘clear’ or ‘almost clear’ on the used ordinal scale (Photoguide, or other Physician's Global Assessment) . To reach this Photoguide stage with the HECSI, an estimated reduction of 54 points or 70% is needed, based on the results of the current study (Table ).…”

New Insights into the Nephroprotective Potential of Lercanidipine

“…As a result of the concomitant use of CsA (CYP3A4 substrate and inhibitor), the bioavailability of lercanidipine increased three-fold, while the plasma concentration of ciclosporin increased by 21%. In patients taking CsA and lercanidipine concomitantly, it is important to monitor CsA concentrations due to the possibility of side effects [ 24 , 71 , 76 , 77 ]. The oral bioavailability of lercanidipine will also be enhanced by more specific CYP3A4 inhibitors, for example grapefruit juice.…”