Alitretinoin 10mg capsules

Background: Hand eczema is common and a cause of morbidity and occupational disability. When education, irritant/contact allergen avoidance, moisturisation and topical corticosteroids are insufficient to control chronic hand eczema, ultraviolet therapy or systemic immune-modifying drugs are used. There is no treatment pathway generally accepted by UK dermatologists. Primary objective: Compare alitretinoin and ultraviolet therapy as first-line therapy in terms of disease activity at 12 weeks post planned start of treatment. Design: Prospective, multicentre, open-label, two-arm parallel group, adaptive randomised controlled trial with one planned interim analysis, and an economic evaluation. Setting: UK secondary care dermatology outpatient clinics. Participants: Patients with severe chronic hand eczema unresponsive to at least 4 weeks of treatment with potent topical corticosteroids. Primary end point: Natural logarithm of the Hand Eczema Severity Index + 1, 12 weeks post planned start of treatment. Randomisation: Participants randomised 1 : 1 by minimisation to alitretinoin or ultraviolet therapy for 12 to 24 weeks. Blinding: Blinded primary end-point assessor. Results: Intention-to-treat population: 441 (100.0%) participants; 220 (49.9%) alitretinoin and 221 (50.1%) ultraviolet therapy. At least one dose was received by 212 (96.4%) alitretinoin and 196 (88.7%) ultraviolet therapy participants. Primary outcome: = 0.0003 at 12 weeks. There was no evidence of a difference at 24 or 52 weeks, with the estimated fold change (95% confidence interval) equal to 0.92 (0.798 to 1.08) and 1.27 (0.97 to 1.67), respectively. Primary analysis results were consistent for secondary end points: Fifty-nine per cent allocated to alitretinoin and 61% allocated to ultraviolet therapy achieved a clear/almost clear assessment during the trial period. Differential treatment compliance observed: 145 (65.9%) alitretinoin and 53 (24.0%) ultraviolet therapy participants confirmed compliance (≥ 80% received, no treatment breaks > 7 days during first 12 weeks). High levels of missing data were observed. Safety: One hundred and thirty-five reportable adverse events across 79 participants, 55 (25.0%) alitretinoin and 24 (10.9%) ultraviolet therapy. Four serious adverse events (two alitretinoin, two ultraviolet therapy). Four pregnancies reported (three alitretinoin, one ultraviolet therapy). No new safety signals were detected. Conclusion: As a first-line therapy, alitretinoin showed more rapid improvement and superiority to ultraviolet therapy at week 12. This difference was not observed at later time points. Alitretinoin is cost-effective at weeks 12 and 52. Ultraviolet therapy is cost-effective after 10 years, with a high degree of uncertainty. Hand eczema severity index may be a useful primary outcome measure for hand eczema trials; ALPHA results will inform future trials. Limitations: Treatment compliance was poor for ultraviolet therapy. Regular twice weekly treatment was not received by most patients. Assessment of long-term effects of randomised treatments was complicated by use of second-line treatments post treatment phase. Further work: Further analysis of substudies and pilot data will provide valuable information for future studies. A clear need for better therapeutic approaches for severe chronic hand eczema remains. Future studies will need to further address long-term benefits of treatments given. Trial registration: This trial is registered as ISRCTN80206075. Funding: ; Vol. 28, No. 59. See the NIHR Funding and Awards website for further award information.

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Hidradenitis suppurativa (HS) is a debilitating chronic skin disorder characterized by painful inflammatory nodules, abscesses and sinus tracts involving intertriginous areas and has an adverse impact on patient quality of life. Over the past decade, the therapeutic options of HS have increased significantly to comprise multiple modalities, including topical medication, systemic therapies (mainly antibiotics, retinoids, and biologics), surgical approaches, and lifestyle modifications. Biologics alone or in combination with surgery remain the treatment of choice for moderate to severe disease. However, non-biologic therapies (including retinoids) may be used as monotherapy for mild disease and in combination with biologics and surgical treatment in moderate to severe disease. Retinoids, specifically isotretinoin, acitretin, and alitretinoin, are historically used in the management of HS, supported by anecdotal evidence and with variable treatment response. Although the current American and European guidelines offer different recommendations on the use of retinoids in HS, retinoids remain a valuable ally in HS management. This review provides a comprehensive analysis of the current scientific literature on retinoid therapy (topical and systemic) in HS, highlighting disparities in mechanisms of action, efficacy, and safety to clarify their role in HS treatment.

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INTRODUCTION: Evidence for moderate to severe chronic hand eczema (CHE) treatments in clinical practice is limited. The objective was to investigate treatment patterns in patients with moderate to severe CHE, and in those with an inadequate response to topical corticosteroids (TCS) or in whom TCS were contraindicated. METHODS: This was a multinational retrospective physician chart review. Physicians who routinely diagnosed and treated CHE were recruited in Canada, France, Germany, Italy, Spain, and the UK and provided data on adult patients with moderate to severe CHE treated with TCS over the past 12 months or for whom TCS were contraindicated. RESULTS: A total of 292 physicians provided data on 1939 patients. Worst severity of CHE in the 12-month study period was judged by the physician to be moderate in 56.8% and severe in 43.2% of patients. Overall, 6.7% of patients received topical calcineurin inhibitors, 3.9% phototherapy, 6.8% alitretinoin, 11.1% traditional orals (acitretin, azathioprine, oral corticosteroids, cyclosporine, methotrexate), 8.0% biologics, and 1.7% oral Janus kinase (JAK) inhibitors. An inadequate response or contraindication to TCS was reported in 39.9% of patients (27.4% progressed to phototherapy/systemics; 12.1% with adverse events or an inadequate response to high/ultra-high potency TCS, and 0.4% contraindicated). Among these patients, the highest line of treatment during the 12-month period was biologics in 29.2%, alitretinoin in 22.3%, oral JAK inhibitors in 5.1%, traditional orals in 33.3%, and phototherapy in 9.6% of patients. There were no significant differences in phototherapy/systemic treatments between patients with moderate and severe disease in this subgroup. CONCLUSIONS: Despite being a first-line treatment, 40% of patients with CHE were inadequately treated with or contraindicated to TCS. Over one-quarter of patients progressed to phototherapy or systemic therapy. These results suggest a lack of effective and well-tolerated topical treatment options in CHE. Graphical Abstract available for this article.

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BACKGROUND: Acitretin, a synthetic vitamin A derivative, is the most studied and widely used oral retinoid for ichthyoses. Its major disadvantage is the need for contraceptive measures during 3 years after discontinuation. An alternative is needed for women of childbearing age. With alitretinoin, another retinoid, pregnancy is considered safe 1 month after discontinuation. OBJECTIVES: The aim of this study was to provide evidence for alitretinoin as an alternative for acitretin for ichthyosis in women of childbearing age. Our experience is shared in a case series combined with an overview of the current literature. METHODS: Nine women of childbearing age (19-31 years, median 21) with different subtypes of ichthyosis (autosomal recessive congenital ichthyosis, (superficial) epidermolytic ichthyosis, erythrokeratoderma variabilis, and epidermolytic epidermal nevi, a mosaic form of epidermolytic ichthyosis) were included and treated with 30 mg alitretinoin during 2-28 months. Severity was measured by Ichthyosis Area Severity Index (IASI) and Investigator Global Assessment (IGA). A literature search in Pubmed using the Mesh terms "alitretinoin," "skin diseases, genetic" and "ichthyosis" was performed. RESULTS: Significant reduction in the mean scores of IGA, IASI-erythema, IASI-scaling, and IASI-total was seen. Seven patients are still being treated, 1 patient stopped to become pregnant, 1 patient discontinued due to financial reasons. Observed side effects were reversible headache (n = 6), asteatotic eczema (n = 1), "not feeling well" temporarily (n = 1), and easier blistering of the feet (n = 1). The literature search resulted in six case reports and case series about alitretinoin in ichthyosis and ichthyosis syndromes with in total 29 patients. The vast majority of articles (21/29) reported significant improvement or even complete remission of skin symptoms. However, validated outcome measures to support these results were lacking. Side effects (n = 16) were relatively mild, except for benign intracranial hypertension (n = 1) and autoimmune hypothyroidism (n = 1). CONCLUSION: Our study shows, with validated outcome measures, that alitretinoin is effective to mitigate the symptoms of ichthyosis in women of childbearing age and a suitable alternative to acitretin.

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BACKGROUND: Effective treatment options for patients with chronic hand eczema (CHE) are scarce. Dupilumab is licensed for the treatment of moderate-to-severe atopic dermatitis and has shown promising results for the treatment of hand eczema in other studies. OBJECTIVES: To evaluate the efficacy and safety of dupilumab in adult patients with severe CHE (subtypes recurrent vesicular hand eczema or chronic fissured hand eczema) who have an inadequate response/intolerance to alitretinoin, or when alitretinoin is medically inadvisable. METHODS: In this 16-week, randomized, double-blind, placebo-controlled proof-of-concept phase IIb trial, patients with severe CHE were randomized 2 : 1 to dupilumab 300 mg or placebo subcutaneously every 2 weeks. Patients visited the outpatient clinic at the initiation of the study drug, and every 4 weeks until 16 weeks of treatment. The primary endpoint was the proportion of patients achieving at least a 75% improvement on the Hand Eczema Severity Index score (HECSI-75) at week 16. Adverse events were monitored during each visit. The study was registered on ClinicalTrials.gov (identifier NCT04512339). RESULTS: In total, 30 patients were randomized, and 29 patients received the assigned study drug (dupilumab n = 20, placebo n = 9). At week 16, more patients achieved HECSI-75 in the dupilumab group than in the placebo group {95% [95% confidence interval (CI) 73.1-99.7] vs. 33% [95% CI 9.0-69.1]}. Dupilumab also showed greater least square mean percentage change from baseline to week 16 in peak pruritus Numerical Rating Scale compared with placebo [-66.5 ± 10.7 (95% CI -88.6 to -44.5) vs. -25.3 ± 17.0 (95% CI -60.1-9.4)]. Adverse events were similar for the dupilumab and placebo groups and were mostly mild. There were no serious adverse events, nor did any of the adverse events lead to discontinuation of the study drug. CONCLUSIONS: Dupilumab was efficacious and well tolerated. Larger studies of longer duration are needed to provide more evidence on the -efficacy of dupilumab in CHE. Moreover, larger studies could also enable comparisons between clinical subtypes or aetiological -diagnoses.

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Palmoplantar plaque psoriasis is more resistant to therapy compared to other phenotypes of psoriasis. To our knowledge, there are no reports of the efficacy of Janus kinase (JAK) inhibitors for palmoplantar plaque psoriasis. Two adult females presented with more than 6-year histories of severe palmoplantar plaque psoriasis. The first patient had failed topical therapies, phototherapy, acitretin, and secukinumab. The second patient had failed topical therapies and systemic agents including alitretinoin, cyclosporine, apremilast, ustekinumab, ixekizumab, and risankizumab. Both cases were switched to upadacitinib 15 mg daily, with a complete response by 3 months of therapy and no adverse events. The first patient had slightly elevated fasting triglyceride and the second patient had elevated ALT, both of which are being monitored. This case series highlights the efficacy of upadacitinib in two patients with refractory palmoplantar plaque psoriasis. JAK1 inhibitors may be considered as third-line therapeutic options in patients with refractory palmoplantar plaque psoriasis and no contraindications to JAK inhibitors.

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Preeclampsia (PE) is a major pregnancy-specific cardiovascular complication posing latent life-threatening risks to mothers and neonates. The contribution of immune dysregulation to PE is not fully understood, highlighting the need to explore molecular markers and their relationship with immune infiltration to potentially inform therapeutic strategies. We used bioinformatics tools to analyze gene expression data from the Gene Expression Omnibus (GEO) database using the GEOquery package in R. Differential expression analysis was performed using the DESeq2 and limma packages, followed by analysis of variance to identify immune-related differentially expressed genes (DEGs). Several machine learning algorithms, including least absolute shrinkage and selection operator (LASSO), bagged trees, and random forest (RF), were used to select immune-related signaling genes closely associated with the occurrence of PE. Our analysis identified 34 immune source-related DEGs. Using the identified PE- and immune source-related genes, we constructed a diagnostic forecasting model employing several ML algorithms. We identified six types of statistically significant immune cells in patients with PE and discovered a strong relationship between biomarkers and immune cells. Moreover, the immune-derived hub genes for PE exhibited strong binding capabilities with drugs, such as alitretinoin, tretinoin, and acitretin. This study presents a robust prediction model for PE that integrates multiple machine learning-derived immune-related biomarkers. Our results indicate that these biomarkers may outperform previously reported molecular signatures in predicting PE and provide insights into the mechanisms underlying immune dysregulation in PE. Further validation in larger cohorts could lead to their clinical application in PE prediction and treatment.

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