alitretinoin
Sources réglementaires consultées
Indications approuvées
- Eczéma chronique sévère des mains chez l’adulte ne répondant pas aux corticostéroïdes topiques puissants.
Contre-indications
Absolues
- Grossesse, allaitement ou potentiel de grossesse sans respect du plan de prévention ; insuffisance hépatique ou rénale sévère ; hyperlipidémie ou hypothyroïdie non contrôlée ; hypervitaminose A ; tétracyclines ; hypersensibilité aux rétinoïdes ; allergie à l’arachide ou au soja.
Mises en garde cliniques
- Mise en garde majeure · Tératogène humain puissant : contraception efficace dès 1 mois avant jusqu’à 1 mois après, suivi mensuel et tests de grossesse avant, pendant et 1 mois après. Arrêter et orienter en cas de grossesse. — CIMA/AEMPS, ficha técnica 70843
- Mise en garde majeure · Surveiller les lipides, la fonction hépatique, la TSH/T4 et l’état mental ; rechercher céphalées avec troubles visuels liés à une hypertension intracrânienne et arrêter en cas de symptômes sévères. — CIMA/AEMPS, ficha técnica 70843
- Mise en garde majeure · Une anaphylaxie, des idées ou comportements suicidaires, une psychose et une maladie inflammatoire de l’intestin ont été signalés à une fréquence indéterminée. — CIMA/AEMPS, ficha técnica 70843
Interactions médicamenteuses
- SévèreTétracyclines
Mécanisme: Elles augmentent le risque d’hypertension intracrânienne bénigne.
Recommandation: L’usage concomitant est contre-indiqué.
CIMA/AEMPS, ficha técnica 70843https://cima.aemps.es/cima/dochtml/ft/70843/FT_70843.html
- SévèreVitamine A ou autres rétinoïdes
Mécanisme: Ils augmentent le risque d’hypervitaminose A et de toxicité des rétinoïdes.
Recommandation: Ne pas utiliser simultanément.
CIMA/AEMPS, ficha técnica 70843https://cima.aemps.es/cima/dochtml/ft/70843/FT_70843.html
- SévèreInhibiteurs puissants du CYP3A4, CYP2C9 ou CYP2C8
Mécanisme: Ils peuvent augmenter l’exposition à l’alitrétinoïne.
Recommandation: Envisager une réduction à 10 mg et surveiller la tolérance.
CIMA/AEMPS, ficha técnica 70843https://cima.aemps.es/cima/dochtml/ft/70843/FT_70843.html
- SévèreAmiodarone et autres substrats du CYP2C8 à marge thérapeutique étroite
Mécanisme: L’alitrétinoïne peut augmenter leur exposition.
Recommandation: L’amiodarone n’est pas recommandée ; utiliser les autres substrats du CYP2C8 avec prudence.
CIMA/AEMPS, ficha técnica 70843https://cima.aemps.es/cima/dochtml/ft/70843/FT_70843.html
Effets indésirables
Communs (≥1%)
Céphalées · Érythème · Nausées · Bouffées vasomotrices · Hypertriglycéridémie ou hypercholestérolémie · Diminution de la TSH ou de la T4 libre
Rares mais graves
Hypertension intracrânienne bénigne · Dépression
Grossesse et allaitement
Contre-indiquée pendant la grossesse et l’allaitement. Le risque tératogène persiste pendant le traitement et jusqu’à 1 mois après.
Bibliographie récente (PubMed)
Chronic hand eczema is a heterogeneous, fluctuating, and long-lasting disease affecting the hands and wrists that substantially affects quality of life. For severe chronic hand eczema, topical corticosteroids are often unsatisfactory and systemic treatment can be required. The aim of the head-to-head, phase 3 DELTA FORCE trial was to evaluate the efficacy and safety of topical delgocitinib cream versus oral alitretinoin, the only currently approved systemic drug for severe chronic hand eczema. This randomised, assessor-masked, trial was conducted at 102 trial centres in Austria, Canada, France, Germany, Italy, Norway, Poland, Slovakia, Spain, and the UK. Adults (aged ≥18 years) with severe chronic hand eczema were randomly assigned (1:1) via an interactive response technology system to delgocitinib cream 20 mg/g (twice daily) or alitretinoin 30 mg (once daily) for up to 24 weeks. The primary endpoint was change in Hand Eczema Severity Index (HECSI) score from baseline to week 12. Efficacy of delgocitinib cream versus alitretinoin was assessed in all eligible randomly assigned patients who had available data at baseline, and safety was assessed in all patients exposed to trial treatment. The trial is registered with ClinicalTrials.gov (NCT05259722) and is complete. Between June 15, 2022, and Dec 5, 2023, 513 (334 [65%] female and 179 [35%] male) patients were randomly assigned to receive delgocitinib cream (n=254) or alitretinoin (n=259). Ten patients were excluded after randomisation due to not meeting eligibility criteria, so the full analysis set consisted of 250 patients in the delgocitinib group and 253 in the alitretinoin group. One patient in the delgocitinib group and three in the alitretinoin group were excluded from the primary analysis as they had missing HECSI data at baseline. A significantly greater least squares mean change in HECSI score from baseline to week 12 was observed with delgocitinib cream (-67·6 [SE 3·4]; n=249) versus alitretinoin (-51·5 [3
Chronic hand eczema (CHE) is a highly prevalent dermatology-related occupational hazard. This condition, which is a distinct diagnosis from atopic dermatitis (AD), can be quite symptomatic with implications for one's personal and professional life. Many therapeutic interventions exist for CHE, and the current study determined-through network meta-analyses (NMAs)-the relative efficacy of the newer treatments for CHE. Data for eligible studies were identified after systematically reviewing the literature in PubMed and Scopus. Eligible studies were those that had an arm investigating the impact of monotherapy on 12- or 16-week changes in Hand Eczema Severity Index (HECSI) scores. We conducted sensitivity analyses where network meta-regressions were performed to (ecologically) adjust for variation due to age and sex. Base and sensitivity analyses were adjusted for disease severity at baseline. We identified 5 eligible studies-across which there were 10 active comparators. Among the active comparators were two treatments approved by the Food and Drug Administration (FDA) and European Medicines Agency (EMA) for the treatment of CHE, namely, alitretinoin 30 mg once daily (oral) and delgocitinib 20 mg/g twice daily (topical). We estimated pairwise relative effects using the mean difference (i.e., mean reduction) in the respective HECSI scores; furthermore, efficacy was ranked with Surface Under the Cumulative Ranking Curve (SUCRA) values. We attempted to contribute to the existing CHE literature by producing comparative information on its treatments' relative efficacy; moreover, we found no published NMA study on available treatments for CHE before the conduct of our work. Our results can guide clinical decision-making.
To report current knowledge on the different clinical phenotypes of adult atopic dermatitis. Possible therapeutic intervention in relation to phenotype is also evaluated. Atopic dermatitis is a chronic inflammatory disease affecting up to 10% of adults. It can manifest with different clinical phenotypes, causing diagnostic difficulties. Long-term is often required and systemic drugs are needed for moderate-to-severe forms. However, few drugs are registered for atopic dermatitis in many countries. Furthermore, limited data exist regarding the treatment in relation to individual clinical phenotypes. Currently, the most relevant data are those for cyclosporine, alitretinoin, and dupilumab. Cyclosporine and dupilumab showed to be effective in the treatment of atopic dermatitis, although in trials and real-life experiences the different phenotypes treated are usually not reported. However, cyclosporine appears to be effective in prurigo nodularis. Alitretinoin is reported to be particularly efficacious for atopic dermatitis of the hands, while it is ineffective for other locations of the disease. Dupilumab demonstrated its efficacy in prurigo nodularis and nummular eczema phenotypes of atopic dermatitis; moreover, especially in elderly patients, its effectiveness seems to be faster if the folds of the limbs are involved.
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. 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. 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). 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. 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, l
Chronic hand eczema (CHE) is a frequent skin disorder affecting up to 10% of the population and strongly reduces Quality of Life (QoL). The first-line therapeutic strategies for the management of CHE include a change of lifestyle, an education program for the skin and the application of specific emollients. Topical corticosteroids or calcineurin inhibitors are the most used anti-inflammatory drugs. However, up to 65% of patients require systemic options. Alitretinoin, a retinoid structurally related to vitamin A, is the first systemic treatment approved in the European Union (EU) for severe CHE refractory to potent topical corticosteroids. This review summarizes the available data on the pharmacokinetics, pharmacodynamics, efficacy, and safety profile of oral alitretinoin for the treatment of CHE. Alitretinoin can be considered as a valid therapeutic option for the treatment of CHE in patients not responding to ordinary treatments. Clinical trials and real-life experiences showed that it acts effectively on both objective and subjective clinical signs, resulting in a significant improvement in QoL of patients. As for other retinoids, caution should be taken in patients with certain chronic diseases (hepatopathies, kidney failure, hyperlipidemia, thyroid dysfunction) or childbearing potential women.