Journal Digest: October 25

Health Technology Assessment: Alitretinoin Versus Phototherapy as the First-Line Treatment in Adults with Severe Chronic Hand Eczema: the ALPHA RCT

The ALPHA study compared the speed and efficacy of oral alitretinoin versus ultraviolet light therapy when treating adults with chronic hand eczema. Wittmann et alfound that alitretinoin was convenient, cost-effective, and led to more rapid improvement after 23 weeks. The study included 441 participants who had severe unresponsive CHE even after topical corticosteroid treatment. After 12 weeks, hand eczema symptoms improved for both groups of patients but improved most for those who took alitretinoin, with an estimated fold change of 0.66 (0.52, 0.82), p = 0.0003. With alitretinoin, 27.6% of patients were clear or almost clear while 23.6% of patients using UV therapy had the same results. Additionally, both groups had a lower median HECSI score. The investigators noted that more research is needed to address the long-term benefits of both treatments.¹

Dermatologic Therapy: Development and Validation of a Patient-Reported Outcome Measure of the Impact of Chronic Hand Eczema on Health-Related Quality of Life: the Hand Eczema Impact Scale (HEIS)

Weisshaar et al developed a new, 9-item, patient-reported outcome measure that is specific to patients with CHE. The Hand Eczema Impact Scale (HEIS) aims to accurately capture the impact of CHE on individuals’ daily lives and track aspects such as physical function and emotional well-being. The development consisted of qualitative interviews with 20 participants combined with the results from a phase 2b trial of 258 patients (NCT03683719). Inter-item correlations (all > 0.50) and confirmatory factor analysis (factor loadings ≥ 0.80) supported unidimensionality of the HEIS score, and mostly provided support for the HEIS Proximal Daily Activity Limitations (PDAL) score. Other psychometric testing such as internal consistency (Cronbach's alpha ≥ 0.89) and test-retest reliability showed strong results (intra-class correlation coefficient ≥ 0.79). These findings show correlations with other quality-of-life measures, validating the performance and reliability of HEIS. The study authors confirm that HEIS can be used in clinical trials and further research to assess the effectiveness of CHE treatments.²

JAAD International: Risk Factors that Limit Use of Oral JAK Inhibitors in Chronic Hand Eczema: Findings from the Danish Skin Cohort

The Danish Skin Cohort‘s recent study analyzed which black-box warnings can apply to patients of CHE using off-label JAK inhibitors. The investigators found that most patients have risk factors that can impact the safety of JAKi use for CHE treatment. 941 adults with CHE were examined for 12 months. Data was collected through register linkage and patient interviews. Of these participants, 81.6% had at least 1risk factor that could potentially impact the use of oral JAKi. The most common risk factors were heavy smoking (current or former), obesity, hypercholesterolemia, and hypertension. Among patients who did not have any risk factors at baseline, 20.2% developed 1 or more risk factors during the study. Andersen et al addressed the limitation that certain risk factors may be unreported. Nonetheless, clinicians should properly assess these risk factors when selecting CHE treatment options.³

Archives of Dermatological Research: Th1 and Th2 Cytokine Expression in Hyperkeratotic Chronic Hand Eczema and the Role of Tofacitinib a Oral JAK Inhibitor

Sardana et al assessed the efficacy of oral tofacitinib while analyzing the tissue cytokines of Th1 and Th2 in patients with CHE. Tofacitinib targets both Th1 and Th2 cell lines and was found to be effective in reducing symptoms of CHE. A total of 21 patients were involved in the trial. All had used one or more other treatment options including topical corticosteroids, methotrexate, and acitretin. Lesional and non-lesional tissue samples were assessed before tofacitinib (5 mg) was prescribed twice daily. Both cytokines were much more elevated in the affected skin, showing that these immune responses are involved in disease progression. More specifically, there was an upregulation of IL-4 [n = 5/11, 1.87-fold increase], TNF-α (n = 5/11, 5.13-fold) and IFN-γ (n = 6/11, 1.98-fold) as compared to uninvolved skin. The average Hand Eczema Severity Index score was 90 at 4 weeks. Adverse effects were observed in 4 patients while 3 patients experienced a relapse in CHE symptoms 7 months after discontinuing tofacitinib. Overall, the study authors verified that tofacitinib was very effective in patients with predominant tissue Th1/Th2 cells related cytokine expression.⁴

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References

1. Wittmann M, Smith IL, Brown ST, et al. Alitretinoin versus phototherapy as the first-line treatment in adults with severe chronic hand eczema: the ALPHA RCT. Health Technol Assess. 2024;28(59):1-123. doi:10.3310/TWQC0141

2. Weisshaar E, Yüksel YT, Agner T, et al. Development and Validation of a Patient-Reported Outcome Measure of the Impact of Chronic Hand Eczema on Health-Related Quality of Life: the Hand Eczema Impact Scale (HEIS). Dermatol Ther (Heidelb). Published online October 21, 2024. doi:10.1007/s13555-024-01267-0

3. Andersen YMF, Sieborg J, Nymand L, et al. Risk factors that limit use of oral JAK inhibitors in chronic hand eczema: Findings from the Danish Skin Cohort. JAAD Int. 2024;17:61-66. Published 2024 Sep 2. doi:10.1016/j.jdin.2024.08.006

4. Sardana K, Sharath S, Khurana A, et al. Th1 and Th2 cytokine expression in hyperkeratotic chronic hand eczema and the role of Tofacitinib a oral JAK inhibitor. Arch Dermatol Res. 2024;316(10):682. Published 2024 Oct 14. doi:10.1007/s00403-024-03438-7