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Archives of Dermatology Aug 2011
Review
Topics: Adult; Alitretinoin; Deafness; Female; Humans; Ichthyosis; Keratitis; Tretinoin
PubMed: 21844472
DOI: 10.1001/archdermatol.2011.216 -
The British Journal of Dermatology Feb 2014Alitretinoin (9-cis-retinoic acid, Toctino(®) ) has been marketed recently for oral therapy for chronic hyperkeratotic hand eczema. As alitretinoin is highly lipophilic... (Clinical Trial)
Clinical Trial
BACKGROUND
Alitretinoin (9-cis-retinoic acid, Toctino(®) ) has been marketed recently for oral therapy for chronic hyperkeratotic hand eczema. As alitretinoin is highly lipophilic and metabolized mainly in the liver, it is currently considered to be contraindicated in patients with liver disease. However, the pharmacokinetics and metabolism of alitretinoin have not been studied in these patients.
OBJECTIVES
To study the single-dose pharmacokinetics and metabolism of alitretinoin and its metabolites in patients with cirrhosis following oral administration.
METHODS
Eight patients with cirrhosis and eight matched volunteer healthy controls were given a single 30-mg oral dose of alitretinoin. Blood and urine samples were collected during the following 24-h study period. Samples were analysed for alitretinoin and for known metabolites using reverse-phase high-performance liquid chromatography. The pharmacokinetics were then evaluated using standard noncompartmental models.
RESULTS
No significant differences were found between healthy controls and patients with cirrhosis when analysing the pharmacokinetic parameters of alitretinoin and its metabolites. Thus, the mean half-lives of alitretinoin were 5·3 and 5·6 h (P = 0.733) and the oral clearances were 1·92 and 1·39 L h(-1) kg(-1) (P = 0·243) in the patient group and the healthy control group, respectively.
CONCLUSIONS
The metabolism and pharmacokinetics of alitretinoin following oral administration of the recommended dose of 30 mg for the treatment of severe hand eczema were similar in patients with cirrhosis and in healthy controls. If indicated, alitretinoin can be used in these patients with careful and close monitoring.
Topics: Administration, Oral; Aged; Alitretinoin; Area Under Curve; Dermatologic Agents; Eczema; Female; Hand Dermatoses; Humans; Liver Cirrhosis; Male; Middle Aged; Tretinoin
PubMed: 23909409
DOI: 10.1111/bjd.12546 -
BMJ Open Feb 2022Hand eczema (HE) is one of the most common skin disorders and an important cause for morbidity and occupational disability. The 1-year prevalence of HE is estimated to...
INTRODUCTION
Hand eczema (HE) is one of the most common skin disorders and an important cause for morbidity and occupational disability. The 1-year prevalence of HE is estimated to be up to 10% and it is estimated that 5%-7% of those develop severe chronic HE. However, current clinical evidence is not compelling enough to guide clinical practice. In a survey among 194 UK dermatologists the most frequent first choice approaches were psoralen combined with ultraviolet A (UVA) treatment (PUVA), oral steroids and alitretinoin (AL). When asked which strategy was most efficient for long-term outcome 20% of clinicians indicated they did not know; 43% of clinicians reported AL and 30% reported PUVA.
METHODS AND ANALYSIS
ALPHA is a multicentre, open, prospective, two-arm parallel group, randomised controlled trial comparing PUVA and AL with a planned sample size re-estimation. Between 500 and 780 participants will be randomised on a 1:1 basis. The physician's global assessment (PGA) will direct treatment after randomisation, non-responders will be treated according to usual clinical practice; providing valuable pilot data on second line therapeutic approaches to inform future trials.Assessments will be conducted up to 52 weeks post randomisation. The primary outcome measure is the Hand Eczema Severity Index at 12 weeks. Secondary outcome measures include modified Total Lesion Symptom Score, PGA, time to relapse, patient reported outcome measures and DNA extraction and assessment of genetic variants. A substudy on molecular inflammatory mediators will provide information on subgroup specific treatment responses. Photographs will be taken and HE severity assessed by a central review panel.
ETHICS AND DISSEMINATION
Ethics approval was obtained from Leeds West Research Ethics Committee (14/YH/1259).Trial results will be disseminated at relevant clinical conferences and societies, published in peer-reviewed journals and through relevant patient groups.
TRIAL REGISTRATION NUMBER
ISRCTN80206075.
Topics: Humans; Alitretinoin; Eczema; Multicenter Studies as Topic; Patient Reported Outcome Measures; Prospective Studies; Randomized Controlled Trials as Topic
PubMed: 35197358
DOI: 10.1136/bmjopen-2021-060029 -
The British Journal of Dermatology Nov 2012Palmoplantar pustular psoriasis is often recalcitrant to therapy. Here we evaluated the therapeutic effect of alitretinoin in patients with recalcitrant palmoplantar...
BACKGROUND
Palmoplantar pustular psoriasis is often recalcitrant to therapy. Here we evaluated the therapeutic effect of alitretinoin in patients with recalcitrant palmoplantar pustular psoriasis and investigated subsequent immunopathological alterations.
METHODS
Seven patients with palmoplantar pustular psoriasis were treated with oral alitretinoin 30 mg once daily for 12 weeks. Efficacy was assessed by palmoplantar pustular psoriasis area and severity index (PPPASI), visual analogue scales (VAS) on intensity of pain and pruritus and an overall patient assessment. Immunohistochemical staining for neutrophil elastase, CD3, CD4, CD8, CD1a CD11c, CD303,CD68, CD69, CD208 and HLA-DR was on lesional skin biopsies obtained before and after 12 weeks of treatment.
RESULTS
PPPASI and VAS for pruritus and pain decreased significantly after 12 weeks of treatment with alitretinoin. The overall patient assessment ranged from 60% to 90% clinical improvement. In correlation with clinical improvement a significant reduction, particularly of neutrophils, macrophages and dendritic cells, was also observed in the skin sections. Alitretinoin was well tolerated except for headache during the first month of treatment in two patients. Limitations of the study are a missing control group and the concomitant usage of topical therapy.
DISCUSSION
Our findings suggest that alitretinoin may represent a new and promising therapy for recalcitrant palmo-plantar psoriasis and warrants further controlled studies to confirm efficacy and safety of alitretinoin in this disease.
Topics: Adult; Aged; Alitretinoin; Antineoplastic Agents; Female; Humans; Inflammation; Male; Middle Aged; Psoriasis; Treatment Outcome; Tretinoin; Young Adult
PubMed: 22612660
DOI: 10.1111/j.1365-2133.2012.11063.x -
Dermatology (Basel, Switzerland) 2014Treatment of nail lichen planus (LP) is difficult and an optimal therapy is lacking. (Review)
Review
BACKGROUND
Treatment of nail lichen planus (LP) is difficult and an optimal therapy is lacking.
OBJECTIVE
To report additional cases to the scant existing literature to learn more about therapeutic options for nail LP.
METHODS
A regimen of 30 mg alitretinoin daily in 2 cases of nail LP over a period of 9 and 8 months, respectively.
RESULTS
In either case, nail changes showed marked improvement under oral alitretinoin therapy within 2 and 4 months, respectively. In both patients, affected nails with end-stage destructive pterygium were resistant to any previously applied therapy.
CONCLUSION
Alitretinoin is an effective treatment option for nail LP. We recommend early diagnosis of nail LP and early initiation of systemic therapy with alitretinoin to prevent the development of pterygium and permanent nail damage. However, further clinical studies are needed to establish reliable guidelines for nail LP therapy.
Topics: Alitretinoin; Antineoplastic Agents; Female; Fingers; Humans; Lichen Planus; Male; Middle Aged; Nail Diseases; Nails, Malformed; Tretinoin
PubMed: 25322730
DOI: 10.1159/000365655 -
The British Journal of Dermatology Oct 2021Oral alitretinoin is a retinoid used for severe chronic hand eczema. Although caution is recommended for patients with uncontrolled dyslipidaemia or cardiovascular risk...
BACKGROUND
Oral alitretinoin is a retinoid used for severe chronic hand eczema. Although caution is recommended for patients with uncontrolled dyslipidaemia or cardiovascular risk factors, the actual atherothrombotic risk has not been investigated thus far.
OBJECTIVES
To detect any excess of atherothrombotic events among patients exposed to alitretinoin, during treatment or in the 2 years following initiation.
METHODS
Using the French Health Insurance database, we compared the number of patients who had an atherothrombotic event (coronary artery disease, ischaemic stroke or peripheral artery disease requiring revascularization) in the population exposed to oral alitretinoin vs. the general population of the same age, sex and baseline cardiovascular risk, using standardized morbidity ratios (SMRs).
RESULTS
Between 2009 and 2017, 19 513 patients were exposed to oral alitretinoin in France. Sixty-four (0·3%) patients had an atherothrombotic event while on alitretinoin. Patients receiving alitretinoin experienced no more atherothrombotic events than the general population: patients without cardiovascular risk factors or previous atherothrombotic events had a SMR of 0·65 [95% confidence interval (CI) 0·26-1·34] during alitretinoin treatment, and 1·21 (95% CI 0·90-1·59) in the 2 years following initiation; patients with cardiovascular risk factors or previous atherothrombotic events had a SMR of 0·82 (95% CI 0·60-1·08) during alitretinoin treatment and 0·95 (95% CI 0·82-1·09) in the 2 years following initiation. Taken separately, SMRs for each outcome did not increase either.
CONCLUSIONS
These data from an exhaustive nationwide population-based study do not support an increase in the incidence of atherothrombotic events with alitretinoin use, regardless of the baseline cardiovascular risk of the patient.
Topics: Alitretinoin; Brain Ischemia; Cohort Studies; Dermatologic Agents; Humans; Stroke; Tretinoin
PubMed: 33735442
DOI: 10.1111/bjd.20069 -
The Journal of Dermatology Nov 2019Alitretinoin is the only systemic agent approved for the treatment of severe chronic hand eczema (CHE) unresponsive to potent topical corticosteroids. Clinical trials...
Alitretinoin is the only systemic agent approved for the treatment of severe chronic hand eczema (CHE) unresponsive to potent topical corticosteroids. Clinical trials have shown the efficacy of oral alitretinoin with topical emollients for CHE treatment, but most studies have failed to reach a therapeutic success rate of 50%. Reasonably, we thought it would be more effective to combine topical corticosteroids with oral alitretinoin, but the concomitant use of topical corticosteroids has not been studied yet. One-hundred and seven Korean patients diagnosed with CHE were recruited. The participants were divided into two groups depending on the concomitant use of topical corticosteroids. Comparative analysis was performed between the combined therapy (alitretinoin and topical corticosteroids) and monotherapy groups (alitretinoin only) by using physician global assessment (PGA), patient's global assessment (PaGA), modified total lesion symptom score (mTLSS), and recurrence rates. The combined therapy group showed a significantly higher treatment success rate than the alitretinoin monotherapy group for all efficacy parameters (PGA: P < 0.001, PaGA: P < 0.001, mTLSS changes: P < 0.001), but there was no significant difference in recurrence rates between the groups (P = 0.266). Combined use of topical corticosteroids is recommended for CHE patients being treated with oral alitretinoin due to clinically rapid and superior effectiveness.
Topics: Administration, Oral; Administration, Topical; Adult; Alitretinoin; Chronic Disease; Dermatologic Agents; Drug Therapy, Combination; Eczema; Emollients; Female; Glucocorticoids; Hand Dermatoses; Humans; Male; Middle Aged; Treatment Outcome
PubMed: 31535403
DOI: 10.1111/1346-8138.15071 -
Dermatology (Basel, Switzerland) 2013Therapy-resistant lichen planus (LP) can be a challenging condition for dermatologists. There are some case reports about successful treatments with alitretinoin of... (Review)
Review
BACKGROUND
Therapy-resistant lichen planus (LP) can be a challenging condition for dermatologists. There are some case reports about successful treatments with alitretinoin of cutaneous and oral, but not of esophageal LP.
OBJECTIVE
We present the unique case of a patient with cutaneous, oral and esophageal LP which was refractory to classical treatment options (topical clobetasol propionate and pimecrolimus, intramuscular triamcinolone acetonide); because of systemic side effects the patient did not tolerate systemic acitretin dosed up to 25 mg daily.
METHODS
Oral alitretinoin was used at a dose of 30 mg daily.
RESULTS
Both oral and skin changes as well as dysphagia completely resolved within 4 weeks without any severe side effects and the drug was used for 6 months. No papules, intraoral striae or dysphagia recurred during the 6 months of treatment. After 4 months the patient relapsed with mucosal patches so that a second cycle was initiated for 6 months where oral LP lesions resolved after 4 weeks also (with sporadic mild headache).
CONCLUSION
Further studies are needed to better understand the impact of alitretinoin in LP. Our observation suggests alitretinoin as a new, well-tolerated treatment option for esophageal LP after failed response to conventional treatments.
Topics: Alitretinoin; Antineoplastic Agents; Deglutition Disorders; Esophageal Diseases; Female; Humans; Lichen Planus; Lichen Planus, Oral; Middle Aged; Tretinoin
PubMed: 23948733
DOI: 10.1159/000349980 -
Acta Dermato-venereologica Mar 2015Pityriasis rubra pilaris (PRP) is an uncommon cutaneous disease with disorder of keratinisation. Up to now, systemic retinoids like acitretin or isotretinoin seem to be... (Observational Study)
Observational Study
Pityriasis rubra pilaris (PRP) is an uncommon cutaneous disease with disorder of keratinisation. Up to now, systemic retinoids like acitretin or isotretinoin seem to be the most effective therapeutic agents. However, no large trials on this rare disease have been published and no standardised treatment has been established so far. Recently, single case reports demonstrate beneficial effects of alitretinoin (9-cis retinoic acid) in patients with PRP. We performed a retrospective observational analysis of type I adult-onset patients with PRP (n = 5) treated with systemic alitretinoin in our department. Alitretinoin was highly effective in the treatment of PRP in 4 of 5 cases. PASI score was reduced significantly in the alitretinoin responders. We assume that alitretinoin could serve as an additional effective systemic treatment option for type I adult-onset PRP.
Topics: Aged; Aged, 80 and over; Alitretinoin; Female; Humans; Keratolytic Agents; Male; Middle Aged; Pityriasis Rubra Pilaris; Remission Induction; Retrospective Studies; Treatment Outcome; Tretinoin
PubMed: 24995552
DOI: 10.2340/00015555-1928 -
The British Journal of Dermatology Feb 2010Patients with severe chronic hand eczema (CHE) often respond to therapy with oral alitretinoin (9-cis retinoic acid). However, the efficacy of alitretinoin after disease... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Patients with severe chronic hand eczema (CHE) often respond to therapy with oral alitretinoin (9-cis retinoic acid). However, the efficacy of alitretinoin after disease relapse has not been demonstrated.
OBJECTIVES
To assess the efficacy and safety of a second course of oral alitretinoin in patients with severe CHE who relapsed after achieving 'clear' or 'almost clear' hands following a previous course of alitretinoin.
METHODS
The double-blind study included 117 patients with CHE who had responded to therapy in an earlier clinical trial and subsequently relapsed. Patients were randomized to receive their previous treatment or placebo. Treatment was alitretinoin 30 mg or 10 mg or placebo given once daily for 12-24 weeks. Response was defined as an overall Physician's Global Assessment rating of 'clear' or 'almost clear' hands at the end of therapy.
RESULTS
Response rates were 80% in patients retreated with 30 mg alitretinoin compared with 8% for placebo (P < 0.001). In patients retreated with 10 mg alitretinoin response rates were 48%, compared with 10% in the placebo group. Alitretinoin was well tolerated. Adverse reactions comprised typical retinoid class effects, and no late-arising side-effects were observed during this second course of treatment.
CONCLUSIONS
The majority of patients with CHE who previously achieved 'clear' or 'almost clear' hands following treatment with alitretinoin 30 mg per day also responded to a second course of treatment. Retreatment was well tolerated. Intermittent treatment with alitretinoin is suitable for the long-term management of CHE.
Topics: Administration, Oral; Alitretinoin; Chronic Disease; Dermatologic Agents; Double-Blind Method; Eczema; Female; Hand Dermatoses; Humans; Male; Middle Aged; Recurrence; Retreatment; Time Factors; Treatment Outcome; Tretinoin
PubMed: 19906075
DOI: 10.1111/j.1365-2133.2009.09572.x