alitretinoin and Chronic-Disease

Chronic hand dermatitis is a debilitating inflammatory dermatosis that has a significant impact on the quality of life of those affected. Alitretinoin is an oral retinoid which has proven efficacy and safety in the treatment of chronic hand dermatitis through randomized controlled trials. Real-world evidence, information gathered in the clinic or community setting, as opposed to a research environment, can complement knowledge gained from clinical trials. Herein, real-world evidence supporting the safety and effectiveness of alitretinoin in the management of chronic hand dermatitis will be reviewed.

Topics: Administration, Oral; Alitretinoin; Chronic Disease; Eczema; Hand Dermatoses; Humans; Randomized Controlled Trials as Topic; Retinoids

Alitretinoin is an endogenous vitamin A derivative, 9-cis-retinoic acid. Its anti-inflammatory and immunomodulatory efficacy results from controlling leukocyte activity and cytokine production in keratinocytes. We describe three patients with severe chronic hand eczema accompanied by nail dystrophy, which was treated with alitretinoin 30 mg. Clinical evaluation at 6 months showed complete or almost complete clearing of the nail lesions. We also briefly review the literature reporting on nail dystrophy and alitretinoin treatment. There is some evidence of the clinical effect of retinoids on nail formation, owing to the presence of retinoid receptors on the nail matrix. Further studies are required to better understand the impact of alitretinoin in nail diseases. Our observation supports alitretinoin as a treatment option in retinoid-responsive dermatoses associated with nail involvement.

Topics: Adult; Alitretinoin; Anti-Inflammatory Agents; Chronic Disease; Dermatologic Agents; Eczema; Female; Hand Dermatoses; Humans; Male; Middle Aged; Nail Diseases; Treatment Outcome; Tretinoin

Management of hand eczema is complex because of the broad range of different pathogeneses, courses, and prognoses. Furthermore, the efficacy of most available treatments is not well established and the more severe forms can have a major impact on the patient's quality of life. Patient education, preventive measures, and the use of emollients are the mainstays in the management of hand eczema. High-potency topical corticosteroids are the treatment of choice, with calcineurin inhibitors used for maintenance. Phototherapy or systemic treatments are indicated in patients who do not respond to topical treatments. Switching from topical treatments should not be delayed to avoid sensitizations, time off work, and a negative impact on quality of life. Alitretinoin is the only oral treatment approved for use in chronic hand eczema.

Topics: Adrenal Cortex Hormones; Alitretinoin; Calcineurin Inhibitors; Chronic Disease; Combined Modality Therapy; Dermatitis, Contact; Dermatologic Agents; Disease Management; Eczema; Emollients; Gloves, Protective; Hand Dermatoses; Humans; Immunosuppressive Agents; Occupational Diseases; Phototherapy; Practice Guidelines as Topic; Quality of Life; Tretinoin

The management of hand eczema, more readily called chronic hand dermatitis, is complex. This heaviness is related not only to the disease itself by its different clinical forms but also the multiplicity and diversity of etiological factors, triggering / maintaining or aggravating factors. The repeated therapeutic failures are ransom of incorrect information about the disease and its environment, a lack of clarity in the prescription and duration of treatment in general too short. The reference treatment is high potency topical steroids with or without occlusion for 4-8 weeks followed by alitretinoin 30 mg / day for at least 3-6 months with a monthly lipid and liver monitoring and mandatory monthly pregnancy test in women of childbearing. Associated measures and patient education are the cornerstones of successful treatment. Other alternative treatments such as phototherapy, methotrexate, cyclosporin, mycophenolate mofetil etc. can be considered in case of resistance or for clearing followed by topical treatments.

Topics: Adrenal Cortex Hormones; Algorithms; Alitretinoin; Anti-Bacterial Agents; Chronic Disease; Dermatologic Agents; Disease Management; Drug Monitoring; Drug Therapy, Combination; Eczema; Emollients; Female; Hand Dermatoses; Histamine Antagonists; Humans; Immunosuppressive Agents; Male; Patient Education as Topic; Phototherapy; Pregnancy; Pregnancy Complications; Pregnancy Tests; Salicylic Acid; Tretinoin; Tumor Necrosis Factor-alpha

Oral alitretinoin (9-cis retinoic acid) is an endogenous retinoid related to vitamin A. Studies have shown that oral alitretinoin is effective and well-tolerated in the treatment of severe chronic hand eczema, so that it is approved for this indication. This review summarizes new studies and clinical experience on the off-label use of alitretinoin.

Topics: Alitretinoin; Chronic Disease; Dermatologic Agents; Drug-Related Side Effects and Adverse Reactions; Eczema; Evidence-Based Medicine; Hand Dermatoses; Humans; Off-Label Use; Treatment Outcome; Tretinoin

Alitretinoin is an endogenous retinoid related to vitamin A. Studies have shown that oral alitretinoin is effective and well tolerated in the treatment of severe chronic hand eczema. This review summarizes the clinical pharmacokinetic and pharmacodynamic data from a number of studies involving alitretinoin. These include the effect of food on the pharmacokinetics of alitretinoin, interactions between alitretinoin and ketoconazole, simvastatin or cyclosporin A, the effect of alitretinoin on the pharmacokinetics of a combined oral contraceptive, alitretinoin in seminal fluid after repeated dosing, and the pharmacokinetics of alitretinoin and its metabolites in a clinical setting.

Topics: Administration, Oral; Alitretinoin; Animals; Chronic Disease; Dermatologic Agents; Drug Interactions; Eczema; Food-Drug Interactions; Hand Dermatoses; Humans; Tretinoin

Topics: Administration, Cutaneous; Administration, Oral; Adolescent; Adrenal Cortex Hormones; Aged; Alitretinoin; Chronic Disease; Eczema; Evidence-Based Medicine; Female; Follow-Up Studies; Hand Dermatoses; Humans; Immunosuppressive Agents; Male; Middle Aged; Randomized Controlled Trials as Topic; Retinoids; Risk Assessment; Severity of Illness Index; Treatment Outcome; Tretinoin; Young Adult

This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of alitretinoin for the treatment of adults with severe chronic hand eczema refractory to topical steroid treatment in accordance with the licensed indication, based upon the evidence submission from Basilea Pharmaceuticals Ltd to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal process. The clinical evidence came from a single placebo-controlled randomised controlled trial of daily treatment with alitretinoin for 12-24 weeks, with follow-up for a further 24 weeks, in patients with severe chronic hand eczema (CHE) unresponsive to topical steroids. A statistically significantly greater proportion of patients using alitretinoin achieved the primary end point of clear or almost clear hands by week 24 than did those with placebo. Dose-dependent headache was the most commonly reported adverse event in patients treated with alitretinoin. Serious adverse events were rare, but alitretinoin was associated with increases in both total cholesterol and triglycerides, which has implications for risks of future cardiovascular events. The manufacturer submitted a de novo decision analytic model to estimate, over a time horizon of 3 years, the cost-effectiveness of alitretinoin versus the other relevant comparators identified by NICE. In response to the points of clarification put to it by the ERG regarding the initial submission, the manufacturer provided additional evidence and a revised decision analytic model with a 'placebo' arm. In the manufacturer's original submission to NICE, the base-case incremental cost-effectiveness ratios (ICERs) reported for alitretinoin were 8614 pounds per quality-adjusted life-year (QALY) versus ciclosporin, -469 pounds per QALY versus psoralen + UVA (with alitretinoin dominant) and 10,612 pounds per QALY versus azathioprine. These ICERs decreased as the time horizon was extended in sensitivity analyses. In patients with hyperkeratotic CHE and in women of child-bearing potential, the ICER remained below 20,000. pounds When the health-related quality of life (HRQoL) values used in the model were replaced with those derived from an alternative study, these ICERs increased significantly (to 22,312 pounds per QALY for alitretinoin versus azathioprine). In the revised model, alitretinoin was reported to have an ICER of 12,931 pounds per QALY gained versus sup

Topics: Algorithms; Alitretinoin; Azathioprine; Chronic Disease; Cyclosporine; Dermatologic Agents; Eczema; Hand Dermatoses; Humans; Immunosuppressive Agents; Psychometrics; PUVA Therapy; Quality of Life; Quality-Adjusted Life Years; Tretinoin

Topics: Administration, Oral; Alitretinoin; Chronic Disease; Drug Interactions; Eczema; Hand Dermatoses; Humans; Randomized Controlled Trials as Topic; Tretinoin

After an open preliminary study, two double-blind placebo-controlled randomized studies have confirmed the value of per os alitretinoin in the management of severe chronic hand eczema (CHE). The first showed dose-dependent efficacy and a response defined as "clear" or "almost clear" by 53% of the patients receiving 10-40 mg of alitretinoin per day for 12 weeks. In the second multicenter study (the Bach study), comparing the efficacy of a 12-week alitretinoin treatment (10 mg, 30 mg) to placebo for CHE, a "clear or almost clear" result was observed in 17% (placebo group), 28% (group alitretinoin 10 mg), and 48% (group alitretinoin 30 mg). The onset of action was also significantly shorter in the group treated with 30 mg of alitretinoin compared to the group treated with 10 mg. In a study of randomized retreatment versus placebo, 80% of the patients who were initially responders to alitretinoin and whose CHE had relapsed found "clear" or "almost clear" with alitretinoin 30 mg administered for 12-24 weeks compared to 48% with alitretinoin 10 mg. In all the studies, clinical tolerance was comparable and satisfactory, with the most frequent negative side effects being headache, flushing, and mucocutaneous signs identical to those compared with other retinoids. An increase in cholesterol and/or triglycerides was the most frequent biological side effect. Central hypothyroidism, with no clinical expression, was observed more rarely. These studies confirm that alitretinoin treatment can be envisaged as second-line therapy in adults with CHE that does not respond to well-observed treatment with class potent or very potent dermocorticoids.

Topics: Adult; Alitretinoin; Antineoplastic Agents; Chronic Disease; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Eczema; Hand Dermatoses; Humans; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Tretinoin

Alitretinoin is an endogenous retinoid and acts as a pan-agonist at retinoid receptors, binding with high affinity to both retinoic acid receptors and retinoid X receptors (RXR). Oral alitretinoin once daily is approved for use in patients with severe chronic hand eczema unresponsive to treatment with potent topical corticosteroids. In a large (n = 1032), randomized, double-blind, placebo-controlled, multicentre study (BACH) of up to 24 weeks' duration in adults with severe chronic hand eczema, significantly more patients in the alitretinoin 10 or 30 mg/day groups than in the placebo group responded to treatment with clear/almost clear hands, as assessed by the Physician Global Assessment (PGA) [primary endpoint]. In an extension phase of the BACH study, alitretinoin was effective in patients who relapsed after responding to initial treatment with the drug. Of patients who had responded to initial treatment with alitretinoin 30 mg/day, significantly more alitretinoin 30 mg/day than placebo recipients responded on the PGA with clear/almost clear hands during the extension phase (primary endpoint; 80% vs 8%). Of those who had responded to initial treatment with alitretinoin 10 mg/day, 48% of alitretinoin 10 mg/day and 10% of placebo recipients responded during the extension phase. Alitretinoin was generally well tolerated in clinical trials excluding pregnant women. The most common treatment-emergent adverse events and abnormal laboratory test results were consistent with those previously observed with other oral retinoids and RXR agonists.

Topics: Adult; Alitretinoin; Child; Chronic Disease; Eczema; Female; Hand; Humans; Pregnancy; Randomized Controlled Trials as Topic; Retinoid X Receptors; Skin; Tretinoin

Topics: Administration, Oral; Alitretinoin; Chronic Disease; Clinical Trials as Topic; Dermatologic Agents; Eczema; Glucocorticoids; Hand Dermatoses; Humans; Ointments; Phototherapy; Physical Therapy Modalities; PUVA Therapy; Time Factors; Tretinoin

About 10% of Germans have chronic hand eczema (CHE). Until recently only off-label use agents existed for the treatment of severe CHE cases refractory to topical steroids. In addition, data from controlled clinical trials confirming the efficacy of known treatment strategies was inadequate. With the availability of alitretinoin, 9-cis retinoic acid, this situation may change. In two large clinical trials alitretinoin showed high response rates and a favorable safety profile in the treatment of severe and refractory CHE. Alitretinoin has an anti-inflammatory and immunomodulatory mechanism of action. Acting as a panagonist it binds to retinoic acid receptors A (RAR) and X (RXR). It directly affects cytokine production in keratinocytes and down-regulates leukocyte activity. When used for CHE with detailed patient counseling and appropriate laboratory monitoring, alitretinoin is a promising new option for systemic treatment.

Topics: Alitretinoin; Anti-Infective Agents; Chronic Disease; Clinical Trials as Topic; Dermatologic Agents; Eczema; Hand Dermatoses; Humans; Recurrence; Treatment Outcome; Tretinoin

Topics: Administration, Oral; Alitretinoin; Azathioprine; Chronic Disease; Dermatitis, Allergic Contact; Dermatologic Agents; Eczema; Hand Dermatoses; Humans; Treatment Outcome

Systemic 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.. This 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.. This 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.. NCT03026946; Pre-results.

Topics: Adolescent; Adult; Aged; Alitretinoin; Chronic Disease; Cyclosporine; Dermatologic Agents; Eczema; Female; Hand Dermatoses; Humans; Immunosuppressive Agents; Male; Middle Aged; Patient Reported Outcome Measures; Pregnancy; Prospective Studies; Psychometrics; Quality of Life; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Severity of Illness Index; Young Adult

We examined and evaluated the clinical characteristics of patients who had come to the Allergological and Occupational Dermatology unit in Florence with severe CHE refractory to potent topical corticosteroids. We evaluated the efficacy and safety of alitretinoin and we analyzed the response in the three months of follow-up in the group of patients who completed the cycle of therapy. Improvement in clinical signs and symptoms was assessed using mTLSS and PGA.. All patients were treated daily with single 30-mg doses of oral alitretinoin for 3 to 5 months. The study examined 15 patients with a clinical diagnosis of severe CHE. We found the treatment to be efficient in nine of 13 patients (69%) who were assessed as having "clear" or "almost clear" hands according to PGA.. Even if the number of patients we analyzed was limited and lacked a control group the study allowed us to confirm the efficacy of alitretinoin used in a "real life" clinical experience. In addition, thanks to the adoption of proper emollient therapy and avoidance of any relevant allergens or irritants, no recurrence of the condition was observed among the patients who completed therapy with a PGA value of "mild", "almost clear", or "clear" during three months after treatment.

Topics: Administration, Cutaneous; Administration, Oral; Adolescent; Adult; Alitretinoin; Chronic Disease; Dermatologic Agents; Dose-Response Relationship, Drug; Eczema; Emollients; Female; Follow-Up Studies; Hand Dermatoses; Humans; Male; Middle Aged; Risk Assessment; Severity of Illness Index; Treatment Outcome; Tretinoin

Oral alitretinoin (9-cis-retinoic acid; 9-cis-RA) has shown clinical efficacy in patients with chronic hand eczema (CHE). Herein, we investigated the impact of oral 9-cis-RA on the local and systemic immune response in patients with CHE.. Twenty patients with CHE were treated with oral alitretinoin (10 or 30 mg/day) for at least 24 weeks. Blood samples were taken for flow cytometry, and serum samples were assessed by ELISA to determine immunoglobulin (Ig) levels. Skin biopsies from lesional skin were evaluated immunohistochemically.. Upon 9-cis-RA treatment, improvement of the CHE was observed in all patients. A significant decrease in plasmablasts in the peripheral blood and a significant reduction of serum IgE levels were determined. Furthermore, we detected a significant reduction of CD4+ cells and regulatory T cells in the peripheral blood upon treatment. By contrast, these cell subsets were significantly increased in the affected skin. Cytokine analysis of activated CD154-positive T cells showed a reduction of interleukin (IL)-17 but not of IL-4 or IFN-γ production.. Overall, our data indicate a disease-modifying effect of 9-cis-RA, including a systemic decrease in IL-17-positive cells, but decreased serum IgE and CD23 expression. The increased frequency of FoxP3-positive cells in the skin upon treatment may suggest a mechanism by which hand eczema is therapeutically targeted by 9-cis-RA, but this will need to be proven in the future studies.

Topics: Adult; Aged; Alitretinoin; CD4-Positive T-Lymphocytes; Chronic Disease; Cytokines; Eczema; Female; Flow Cytometry; Hand; Humans; Immunoglobulin E; Immunohistochemistry; Immunologic Factors; Male; Middle Aged; T-Lymphocytes, Regulatory; Tretinoin

Severe chronic hand eczema (sCHE) is a persistent, disfiguring disease that responds poorly to conventional treatment and causes substantial physical and psychological disability. The objective of this study was to evaluate efficacy and safety of oral alitretinoin in sCHE in a Phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group study comparing alitretinoin with placebo. Efficacy was assessed every 4 weeks during treatment and 4 weeks after end of treatment (EOT, 24 weeks); responders were assessed every 4 weeks for a further 48 weeks after EOT. The study was conducted at academic and private dermatology centers. The participants were 596 patients with sCHE refractory to potent topical corticosteroids. Patients were treated with daily oral alitretinoin 30 mg or placebo for up to 24 weeks. Primary endpoint was proportion of responding patients based on Physician Global Assessment (PGA) of "clear" or "almost clear" at EOT. Key secondary endpoints: Patient Global Assessment (PaGA), change in modified Total Lesion Symptom Score (mTLSS), time to response (TTR), extent of disease at EOT, and duration of response (DOR). At EOT, 40% of alitretinoin-treated patients were responders vs 15% placebo-treated patients (odds ratio [OR] = 3.78; P < .001); a greater proportion of alitretinoin-treated patients achieved a PaGA of "cleared" or "almost cleared" (OR = 4.05; P< .001). A greater decrease in mTLSS occurred from baseline to EOT in alitretinoin- vs placebo-treated patients (treatment difference -24% P< .001). Median TTR for responders at EOT was shorter with alitretinoin vs placebo (65 vs 117 days; P< .001). Greater decreases in extent of disease at EOT were observed with alitretinoin vs placebo (treatment difference -22%; P< .001). The most common treatment-emergent adverse event was headache. Alitretinoin significantly improved signs/symptoms of sCHE, was well tolerated in patients refractory to potent topical corticosteroids, and may provide benefit to this population.

Topics: Administration, Oral; Adrenal Cortex Hormones; Adult; Alitretinoin; Chronic Disease; Dermatologic Agents; Double-Blind Method; Eczema; Female; Follow-Up Studies; Hand Dermatoses; Humans; Male; Middle Aged; Severity of Illness Index; Treatment Outcome; Tretinoin

Blinded, controlled studies have found that oral alitretinoin is well tolerated and effective in the treatment of severe chronic hand eczema (CHE).. To assess the safety and efficacy of oral alitretinoin in patients with severe CHE in an open-label study using flexible dosing and a new measurement of patient-relevant benefits.. In total, 249 patients aged 18-75 years with severe CHE unresponsive to treatment with topical corticosteroids received alitretinoin 30 mg once daily for up to 24 weeks. Safety assessments included adverse events (AEs) and laboratory tests. Efficacy assessments included Physician's Global Assessment (PGA), the Modified Total Lesion Symptom Score, Patient's Global Assessment and extent of disease, as well as intensity of pain and pruritus as determined by visual analogue scale (VAS) and a categorical scale for pruritus.. Alitretinoin was well tolerated when given for up to 24 weeks. Dose reduction occurred in 16.5% of patients. Dose interruption was required for 15.7% of patients, most commonly for headache. AEs and laboratory changes comprised effects typical of the retinoid class. A PGA response of 'clear' or 'almost clear' hands was reported for 46.6% of patients, similar to the response rate seen in blinded trials. Results of VAS and categorical assessments of pruritus provided supporting evidence of efficacy, and treatment was assessed as providing meaningful benefits to patients.. Oral alitretinoin 30 mg was well tolerated and effective, and provided distinct therapeutic benefits in severe CHE, as assessed by patients.

Topics: Administration, Oral; Adolescent; Adult; Aged; Alitretinoin; Chronic Disease; Dermatologic Agents; Drug Administration Schedule; Female; Glucocorticoids; Hand Dermatoses; Humans; Male; Middle Aged; Severity of Illness Index; Treatment Failure; Treatment Outcome; Tretinoin; Young Adult

Alitretinoin (9-cis-retinoic acid) is an endogenous derivative of vitamin A and functions as an agonist of both families of nuclear receptors (retinoic acid receptor-α, -β, -γ; retinoid X receptor-α, -β, -γ). It has been investigated in the treatment of chronic hand eczema in many studies in recent years and the results have been promising.. To evaluate the efficacy and safety of oral alitretinoin in the treatment of chronic hand eczema that is refractory to treatment with potent topical corticosteroids and to analyze the long-term response to treatment.. A prospective, observational, descriptive study was undertaken in 15 patients with chronic hand eczema that was refractory to treatment with potent topical corticosteroids. Patients were administered oral alitretinoin 30 mg/d for 3 months followed by 6 months of follow-up.. A complete response, with "clear" hands was obtained in 7 patients (47%), 5 patients (33%) achieved a partial response (almost clear hands), 1 patient (7%) showed substantial improvement, 1 (7%) showed moderate improvement, and 1 patient (7%) did not respond to treatment. Relapse occurred within 6 months of treatment suspension in 54% of cases. The treatment was well tolerated. Side effects, observed in 50% of cases, were mild (headache, elevated lipid levels, slightly elevated transaminase levels, and epigastric pain), except in 1 patient, who had a substantial reduction in thyroid stimulating hormone levels.. The results of our study support the proposal of alitretinoin as an effective and safe short-term and medium-term treatment for chronic hand eczema in patients whose disease is refractory to treatment with potent topical corticosteroids.

Topics: Administration, Cutaneous; Administration, Oral; Adrenal Cortex Hormones; Adult; Aged; Alitretinoin; Child; Chronic Disease; Drug Resistance; Eczema; Female; Hand Dermatoses; Headache; Humans; Hypercholesterolemia; Middle Aged; Occupational Diseases; Prospective Studies; Thyrotropin; Treatment Outcome; Tretinoin

Recent studies have found that alitretinoin can induce clinically significant responses in subjects with severe chronic hand eczema (CHE) unresponsive to topical corticosteroids.. To assess the pharmacokinetics (PK), efficacy and safety of alitretinoin 10 or 30 mg once daily.. This was a randomized, double-blind study, which enrolled 32 subjects aged 18-75 years with CHE unresponsive to potent topical corticosteroids. Subjects received alitretinoin 10 mg (n = 16) or 30 mg (n = 16) once daily for 12 or 24 weeks. Standard PK variables [area under the curve (AUC) of plasma concentration vs. time, maximum plasma concentration (C(max)), time to maximum plasma concentration (t(max)), elimination half-life (t(1/2)), total systemic clearance (CL/F) and volume of distribution (Vd/F)] were determined for alitretinoin and metabolites. Efficacy was assessed using the Physician's Global Assessment (PGA) scale.. Chronic administration of alitretinoin for up to 24 weeks did not result in accumulation or time-dependent changes in the disposition of alitretinoin. Exposure was found to be proportional to dose. Systemic exposure (AUC) to alitretinoin was proportional to dose for 10 and 30 mg alitretinoin; 62.8% of subjects achieved clear/almost clear hands in the 30 mg group and 12.5% in the 10 mg group. Alitretinoin was well tolerated.. Chronic administration of alitretinoin for 12-24 weeks did not lead to accumulation or time-dependent changes in drug exposure. Alitretinoin was effective and well tolerated in the treatment of subjects with moderate or severe CHE unresponsive to potent topical corticosteroids.

Topics: Adolescent; Adult; Aged; Alitretinoin; Chronic Disease; Dermatologic Agents; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Hand Dermatoses; Humans; Male; Middle Aged; Treatment Outcome; Tretinoin; Young Adult

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.. 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.. 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.. 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.. 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

Patients with severe chronic hand eczema (CHE) refractory to topical corticosteroids currently have limited treatment options suited for chronic use, and few controlled clinical studies have investigated new therapies in this setting.. To assess the efficacy and safety of oral alitretinoin (9-cis retinoic acid) taken at 10 mg or 30 mg once daily for up to 24 weeks, compared with placebo control, in the treatment of severe CHE refractory to topical corticosteroids.. A randomized, double-blind, placebo-controlled, prospective, multicentre trial was conducted in 111 dermatology outpatient clinics in Europe and Canada. A total of 1032 patients with severe refractory CHE were randomized in a 1 : 2 : 2 ratio to placebo, or 10 mg or 30 mg of oral alitretinoin once daily for up to 24 weeks. Safety was assessed for all patients during a follow-up period of 4 weeks, and responders were observed for relapse for 24 weeks after the end of therapy. The primary efficacy parameter was Physician Global Assessment of overall CHE severity, with response defined as clear or almost clear hands.. Responses, defined as clear or almost clear hands, were achieved in up to 48% of patients treated with alitretinoin, compared with 17% for placebo (P < 0.001), with up to 75% median reduction in disease signs and symptoms. Treatment was well tolerated, with dose-dependent adverse effects comprising headache, mucocutaneous events, hyperlipidaemia, and decreased free thyroxine and thyroid-stimulating hormone. The median time to relapse, defined as recurrence of 75% of initial signs and symptoms, was 5.5-6.2 months in the absence of anti-eczema medication.. Alitretinoin given at well-tolerated doses induced clearing of CHE in a substantial proportion of patients with severe disease refractory to standard therapy.

Topics: Adolescent; Adult; Aged; Alitretinoin; Chronic Disease; Dermatologic Agents; Dose-Response Relationship, Drug; Drug Administration Routes; Eczema; Epidemiologic Methods; Female; Hand Dermatoses; Humans; Male; Middle Aged; Tretinoin

To assess the efficacy and safety of oral alitretinoin (9-cis-retinoic acid), 10 mg/d, 20 mg/d, and 40 mg/d, compared with placebo control, in the treatment of chronic hand dermatitis.. Multicenter, randomized, double-blind, placebo-control, prospective trial.. A total of 43 outpatient clinics in 10 European countries.. Of 348 patients screened, 319 with moderate or severe refractory chronic hand dermatitis were randomized, in the ratio of 1:1:1:1, to 4 treatment groups and received allocated intervention. Of 75 patients who withdrew, 24 withdrew owing to adverse events.. Placebo or 10 mg, 20 mg, or 40 mg of oral alitretinoin (9-cis-retinoic acid) taken once daily for 12 weeks. Safety was assessed for all patients during a follow-up period of 4 weeks, and responders were observed for a follow-up period of 3 months.. Physician's global assessment of overall chronic hand dermatitis severity.. Alitretinoin led to a significant and dose-dependent improvement in disease status, with responses in up to 53% of patients, and up to a 70% mean reduction in disease signs and symptoms. Treatment was generally well tolerated, with dose-dependent effects comprising headache, flushing, mucocutaneous events, hyperlipidemia, and decreased hemoglobin and decreased free thyroxin levels. Three months after discontinuation of treatment, the rate of relapse was 26%, independent of dose.. Alitretinoin given at well-tolerated doses induced substantial clearing of chronic hand dermatitis in patients refractory to conventional therapy.

Topics: Administration, Oral; Adrenal Cortex Hormones; Alitretinoin; Chronic Disease; Dose-Response Relationship, Drug; Double-Blind Method; Drug Resistance; Female; Follow-Up Studies; Hand Dermatoses; Humans; Male; Middle Aged; Prospective Studies; Recurrence; Treatment Outcome; Tretinoin

9-cis-Retinoic acid (9-cis-RA) has a particular pattern of binding and activating retinoid receptors. Treatment of chronic hand eczema is often refractory to conventional treatment.. Evaluation of oral 9-cis-RA therapy in chronic hand eczema in a pilot study.. Thirty-eight patients with refractory chronic hand eczema were treated in an exploratory open-label study with oral 9-cis-RA.. Twenty-one (55%) showed a very good response, 13 (34%) a good response, 2 (5.5%) a moderate response and 2 (5.5%) no response. Side effects were mild.. 9-cis-RA is a valuable drug when given at low doses to patients with chronic hand eczema.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Alitretinoin; Antineoplastic Agents; Cheilitis; Chronic Disease; Eczema; Female; Flushing; Hand Dermatoses; Headache; Humans; Male; Middle Aged; Patient Satisfaction; Pilot Projects; Severity of Illness Index; Skin; Treatment Outcome; Tretinoin

Topics: Alitretinoin; Chronic Disease; Eczema; Humans; Photosensitivity Disorders; Retinoids; Tretinoin

Alitretinoin is the only systemic agent approved to treat moderate-severe chronic hand eczema (CHE) unresponsive to potent topical corticosteroids. No nationwide Italian data regarding real-life efficacy, safety, and tolerability of treatment are available. The DECISA project (DErmatology Clinics in Italy: Survey on Alitretinoin) retrospectively examined data from a registry including 15 Dermatology Clinics authorized to prescription of alitretinoin for CHE patients. Disease severity was assessed at baseline, and after 3 and 6 months of treatment, using the 5-point Physician Global Assessment (PGA) and the modified Total Lesion-Symptoms-Severity (mTLSS) scores. Between November 2010 and July 2018, data of 248 male and 190 female patients (mean age 49.71 ± 13.20 years) treated with alitretinoin were collected. Of them, 43.2% had irritant contact dermatitis, 22.2% allergic contact dermatitis, 18.0% atopic dermatitis, 16.7% mixed (irritant/allergic) type of eczema. At 3 months, the 420 re-evaluated patients showed significantly reduced mTLSS and PGA (P < .0000001 vs baseline for both); PGA was clear/almost clear in 35.6% of cases. At 6 months, the 341 re-evaluated patients showed significant (P < .0000001) improvement of mTLSS and PGA vs baseline and 3 months (PGA clear/almost clear: 41.4%). Relapses occurred in 125 patients; 58 underwent an additional course of alitretinoin, with similarly good results. No relevant safety issues were reported; 86 patients experienced adverse effects, which forced 40 to prematurely stop treatment. The DECISA project results confirm the real-life efficacy, safety and tolerability of alitretinoin in the treatment of moderate to severe CHE refractory to standard topical therapies.

Topics: Adult; Alitretinoin; Chronic Disease; Dermatologic Agents; Dermatology; Eczema; Female; Hand Dermatoses; Humans; Italy; Male; Middle Aged; Retrospective Studies; Treatment Outcome; Tretinoin

Alitretinoin is a systemic retinoid licensed for use in adult patients suffering from chronic hand eczema recalcitrant to potent topical steroids. Experience with its use in childhood is lacking.. To report on the efficacy and safety of alitretinoin treatment in a cohort of children and adolescents with chronic hand eczema (CHE) and other inflammatory skin diseases.. We performed a retrospective chart review of all consecutive patients under the age of 18 years treated with alitretinoin at our paediatric skin centre. Physician's Global Assessment (PGA) was used as the primary outcome measure.. Thirteen children (9 girls and 4 boys) were enrolled in this study. The median age at start of treatment with alitretinoin was 11.5 years (range 5.8-15.8 years). Nine children were diagnosed with CHE, two with severe atopic dermatitis (AD), and two with inherited ichthyosis [netherton syndrome (NS), autosomal recessive congenital ichthyosis (ARCI)]. Moderate to excellent response (PGA decrease of ≥1 point) was observed in 7 (78%) of the nine patients with CHE, one of the two patients with extensive AD and in the one patient with ARCI. In the remaining four subjects, no convincing effect was documented. Tolerability was overall very good. The most common adverse event was headache in 10 patients (77%) during the initiation of treatment, leading to interruption of therapy in one subject.. Alitretinoin seems to be highly effective and safe for the treatment of paediatric CHE and should thus be considered in children with refractory disease under topical therapy. Larger studies are required to corroborate these findings.

Topics: Adolescent; Adult; Alitretinoin; Child; Child, Preschool; Chronic Disease; Dermatologic Agents; Eczema; Female; Hand Dermatoses; Humans; Male; Retrospective Studies; Treatment Outcome; Tretinoin

Topics: Administration, Oral; Alitretinoin; Chronic Disease; Cyclosporine; Dermatologic Agents; Eczema; Hand Dermatoses; Humans; Patient Safety; Retrospective Studies; Skin; Time Factors; Treatment Outcome

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

The CARPE registry was set up in 2009 to prospectively investigate the management of patients with chronic hand eczema (CHE).. To report comprehensive follow-up data from the CARPE registry.. We investigated sociodemographic and clinical characteristics, provision of medical care, physician-assessed outcomes, and patient-reported outcomes (PROs). Data were collected between 2009 and 2016, with up to 5 years of follow-up, and are reported descriptively.. Overall, 1281 patients were included in the registry (53.7% female). Mean age was 47.0 years. Of the patients, 793 and 231 completed the 2-year follow-up and 5-year follow-up, respectively. At baseline, 5.4% had changed or given up their job because of CHE, the average duration of CHE was 6.1 years, and, in 22.4%, the CHE was severe according to physician global assessment. Systemic treatment (alitretinoin, acitretin, and methotrexate) was prescribed at least once to 39.0% of the patients during the course of the follow-up. Disease severity, quality of life and treatment satisfaction improved over time, and the proportion of patients receiving systemic treatments decreased.. Under continued dermatological care, substantial improvements in disease severity and PROs over time was achieved during the course of the CARPE registry, even in patients with long-standing and severe hand eczema.

Topics: Acitretin; Administration, Cutaneous; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Aged, 80 and over; Alitretinoin; Chronic Disease; Dermatitis, Allergic Contact; Dermatologic Agents; Eczema; Female; Follow-Up Studies; Hand Dermatoses; Humans; Male; Methotrexate; Middle Aged; Outcome Assessment, Health Care; Patient Reported Outcome Measures; PUVA Therapy; Registries; Ultraviolet Therapy; Urea; Young Adult

Topics: Adult; Alitretinoin; Chronic Disease; Dermatologic Agents; Eczema; Female; Hand Dermatoses; Humans; Male; Middle Aged; Republic of Korea; Retrospective Studies; Severity of Illness Index; Treatment Outcome

Treatment of severe hand eczema (HE) that is resistant to topical potent corticosteroid treatment is challenging. In 2013, we surveyed 194 UK dermatologists to obtain information about their usual treatment pathways to inform the choice of the comparator in a trial of alitretinoin in severe HE (ALPHA trial); the results indicated that the treatment approaches favoured by UK dermatologists differ. Psoralen combined with ultraviolet A (PUVA) and alitretinoin were identified as the most frequent first-line treatment options for hyperkeratotic HE, whereas oral corticosteroids were identified as the most frequent first-line treatment for vesicular HE, followed by PUVA and alitretinoin. In terms of potential adverse effects of long-term or repeated use, oral steroids and ciclosporin A were reported to cause most concern. There is uncertainty about which treatment gives the best short and long-term outcomes, because of a lack of definitive randomised controlled trials evaluating the effectiveness of different treatment pathways in severe HE.

Topics: Administration, Oral; Adrenal Cortex Hormones; Alitretinoin; Chronic Disease; Dermatologists; Eczema; Hand Dermatoses; Health Care Surveys; Humans; Keratolytic Agents; Practice Patterns, Physicians'; PUVA Therapy; Tretinoin; United Kingdom

Alitretinoin is approved for the treatment of adults with severe chronic hand eczema (CHE) refractory to potent topical steroids. In the 6 years since launch, approximately 250 000 patients have been treated with alitretinoin.. To compare the postmarketing safety surveillance experience of alitretinoin with data from clinical trials and key safety issues with other retinoids.. An integrated safety analysis of the pivotal studies of alitretinoin and postmarketing adverse event (AE) reports received since approval for alitretinoin were analyzed.. In the pivotal trials, headache, erythema, nausea, increased blood triglycerides and increased blood creatinine phosphokinase were the most frequently reported AEs. Headache, hyperlipidemia and nausea were also frequently reported postmarketing AEs, but depression was relatively more frequently reported than in the pivotal trials. Inflammatory bowel disease and benign intracranial hypertension were rare, and very few cases have been reported in postmarketing surveillance. There have been no reports of teratogenicity in humans consequent to fetal exposure.. Safety data collected in pivotal trials and postmarketing surveillance suggest that alitretinoin is well tolerated by patients with CHE with a relatively low incidence of serious reactions. The adverse reaction profile is congruent with reported effects of other marketed oral retinoids.

Topics: Adult; Alitretinoin; Chronic Disease; Eczema; Female; Hand Dermatoses; Headache; Humans; Pregnancy; Tretinoin

Hand eczema affects nearly 10% of the population. The condition becomes severe and chronic in 5% to 7% of cases and is refractory to topical corticosteroids in 2% to 4%. This study aimed to describe the current use of oral alitretinoin in treating Spanish national health system patients with hand eczema that is refractory to potent topical corticosteroids.. Observational, descriptive, exploratory, cross-sectional study based on the retrospective analysis of records for patients with hand eczema treated with alitretinoin in the Spanish national health system.. We reviewed the records for 62 patients in 13 hospitals in 5 different administrative areas (autonomous communities) of Spain. Alitretinoin was usually used at a dosage of 30mg/d. In most cases the physician judged the clinical response to be satisfactory after a single cycle. The recorded adverse effects were foreseeable and of the type reported for systemic retinoids. The dermatologists agreed that the clinical benefits achieved with alitretinoin favored adherence to treatment and an early return to work.. The results show that oral alitretinoin is being used according to established recommendations and that response is good, with few adverse effects. The dermatologists agreed that the benefits favored adherence and improved the patients' health related quality of life.

Topics: Alitretinoin; Chronic Disease; Cross-Sectional Studies; Eczema; Hand Dermatoses; Humans; Retrospective Studies; Spain; Tretinoin

Acitretin has been used off-label for years to treat chronic hand eczema, but acitretin is less often prescribed as alitretinoïne was approved. This study evaluates both retinoids in a daily practice cohort of patients with severe chronic hand eczema in terms of drug survival and reasons for discontinuation. Patients using alitretinoin or acitretin between 01-01-1994 and 01-08-2015 were included in this retrospective daily practice study and analyzed by Kaplan-Meier drug survival curves. Potential determinants were analyzed by Cox regression analyses. Ninety-five patients were treated with alitretinoin and 109 patients with acitretin. The main reasons for discontinuation were adverse events and cleared hand eczema, 29.5 and 27.4% in alitretinoin versus 43.1 and 23.9% in acitretin. Patients with hyperkeratotic hand eczema had most often a good effect of treatment: 68.3% in alitretinoin and 50.7% in acitretin treatment. The drug survival rates of alitretinoin and acitretin after 12, 24, 36, and 52 weeks were 69.3, 45.1, 19.6, 7.0% and 74.3, 45.5, 33.8, 23.2%, respectively. Alitretinoin and acitretin are effective treatment options for patients with hand eczema. However, both treatments were more effective in patients with hyperkeratotic hand eczema. Fewer patients discontinued alitretinoin compared with acitretin due to adverse events.

Topics: Acitretin; Adult; Aged; Alitretinoin; Chronic Disease; Dermatologic Agents; Eczema; Female; Hand Dermatoses; Humans; Kaplan-Meier Estimate; Keratosis; Male; Middle Aged; Proportional Hazards Models; Remission Induction; Retrospective Studies; Severity of Illness Index; Time Factors; Treatment Outcome; Tretinoin

Chronic hand eczema (CHE) is a common inflammatory skin disease that affects approximately 10% of the population. Systemic alitretinoin has been shown to be effective in patients with CHE who are refractory to topical corticosteroids.. To analyse the impact of alitretinoin on the skin barrier genes and protein expression in the skin lesions of patients with CHE.. Fifteen patients with CHE were treated with 30 mg daily of alitretinoin for up to 27 weeks. Disease severity was assessed using a clinical score. Skin biopsies from all the patients were evaluated before and after therapy for the expression of Ki-67, various skin barrier genes and thymic stromal lymphopoietin (TSLP) by real-time quantitative polymerase chain reaction and immunohistochemistry.. After alitretinoin application, an improvement in the clinical severity of CHE was observed in the majority of patients. Analysis of skin biopsies before treatment showed a significant increase in Ki-67-positive cells in the suprabasal layer and a dysregulated expression of various skin barrier genes, such as claudin 1, loricrin, filaggrin and cytokeratin 10, which were normalized after treatment. TSLP was significantly upregulated in patients with CHE and also normalized after alitretinoin treatment and negatively correlated with filaggrin.. Our data indicate that the expression of barrier genes and proteins was normalized following treatment with alitretinoin in patients with CHE. The change in expression levels of these genes correlated with the clinical efficacy, suggesting that alitretinoin exhibits a disease-modifying activity. TSLP is upregulated in CHE and seems to counteract filaggrin expression in the skin.

Topics: Administration, Cutaneous; Adult; Aged; Alitretinoin; Chronic Disease; Dermatologic Agents; Drug Administration Schedule; Eczema; Epidermis; Female; Filaggrin Proteins; Gene Expression; Hand Dermatoses; Humans; Ki-67 Antigen; Male; Middle Aged; Tight Junction Proteins; Tretinoin

Severe chronic hand eczema (CHE) has a debilitating effect on quality of life (QoL). PASSION evaluated the effectiveness of oral alitretinoin on QoL and work productivity in patients with severe CHE following prescribing guidelines.. A non-interventional, open-label, observational, multicentre study conducted in Germany in fulfilment of German guidelines. Patients (n = 631) were treated with once-daily alitretinoin for ≤24 weeks under standard daily practise conditions. Effectiveness was assessed by Physician Global Assessment (PGA), QoL Assessment (EQ-5D) and work impairment. Tolerability and safety were assessed by adverse event (AE) monitoring.. In total, 279 (44.2%) patients dropped out before Week 24. Of the 631 patients enrolled, 29.8% achieved a PGA rating of clear/almost clear at Week 24. Mean (standard deviation) EQ-5D utility and EQ-5D visual analogue scale scores at baseline were 0.76 (0.25) and 53.6 (23.55), respectively, and increased to 0.94 (0.12) and 80.8 (19.23) at Week 24, indicating improved QoL. At baseline, 49.4%/29.1% of patients reported strong/very strong workplace impairment, respectively, and decreased to 8.5%/1.4%, respectively, at Week 24. AEs were reported in 116 (18.4%) patients. No new safety signals were observed.. Alitretinoin produced marked improvement in the QoL and work productivity of patients with severe CHE.

Topics: Alitretinoin; Antineoplastic Agents; Chronic Disease; Dermatologic Agents; Eczema; Female; Hand Dermatoses; Humans; Male; Middle Aged; Quality of Life; Tretinoin

Alitretinoin is the only approved treatment for severe chronic hand eczema (CHE) refractory to potent topical corticosteroids. This study (FUGETTA) evaluated the effectiveness and impact on quality of life (QoL) of oral alitretinoin in patients with severe refractory CHE in accordance with prescription guidelines.. Open-label, multicenter, noninterventional, observational study conducted in Germany. Patients were treated at their physician's discretion with once-daily alitretinoin 10 mg or 30 mg for a maximum of 24 weeks. Effectiveness was assessed by Physician Global Assessment (PGA) and Dermatology Life Quality Index (DLQI). Adverse events (AEs) were assessed.. The study population included 658 patients (30 mg n = 581; 10 mg n = 77). At baseline, most patients had CHE characterized as severe by PGA (83 %). At last visit, 48 % of patients had a PGA response of clear/almost clear (30 mg: 49 %; 10 mg: 43 %). Mean improvement in DLQI scores at week 24 was 58 % (30 mg: mean [SD] change from baseline -10.4 [8.04]) and 70 % (10 mg: mean [SD] change from baseline -10.8 [7.29]). The overall incidence of AEs was low and similar in both groups.. Alitretinoin produced rapid, marked improvement in QoL of patients with severe CHE.

Topics: Administration, Cutaneous; Adolescent; Adult; Age Distribution; Alitretinoin; Chronic Disease; Dermatologic Agents; Dose-Response Relationship, Drug; Eczema; Female; Germany; Hand Dermatoses; Humans; Middle Aged; Patient Satisfaction; Prevalence; Quality of Life; Severity of Illness Index; Sex Distribution; Treatment Outcome; Tretinoin; Women's Health; Young Adult

Topics: Administration, Oral; Adult; Alitretinoin; Chronic Disease; Dermatologic Agents; Drug Resistance; Female; Humans; Pemphigus, Benign Familial; Tretinoin

The aim of the CARPE registry is to investigate characteristics and medical care in patients affected by chronic hand eczema. Patients are assessed by dermatological examination and patient questionnaire. Socio-economic and clinical data are collected, and quality of life is measured using the Dermatology Life Quality Index (DLQI). A total of 1,163 patients with chronic hand eczema were eligible for analysis (mean age 47.0 years; 54.6% female; mean disease duration 7.6 years). At inclusion, chronic hand eczema was very severe in 23.4%, severe in 47.0%, moderate in 20.1%, and clear or almost clear in 9.6% of patients. Median DLQI was 8.0. In all, 93.8% of patients reported use of topical corticosteroids, 25.6% systemic antihistamines, 28.3% topical calcineurin-inhibitors, 38.0% ultraviolet phototherapy, and 35.3% systemic treatment (19.7% alitretinoin) prior to inclusion in the registry. A significant proportion of patients may not receive adequate treatment according to the guideline on management of hand eczema.

Topics: Administration, Topical; Adolescent; Adult; Aged; Aged, 80 and over; Alitretinoin; Calcineurin Inhibitors; Chronic Disease; Eczema; Female; Germany; Glucocorticoids; Hand Dermatoses; Histamine Antagonists; Humans; Male; Middle Aged; Occupations; Pruritus; Quality of Life; Registries; Severity of Illness Index; Tretinoin; Ultraviolet Therapy; Young Adult

Topics: Alitretinoin; Chronic Disease; Cyclosporine; Dermatologic Agents; Drug Substitution; Eczema; Foot Dermatoses; Hand Dermatoses; Humans; Male; Middle Aged; Nail Diseases; Nails, Malformed; Time Factors; Treatment Outcome; Tretinoin

The treatment of moderate to severe chronic hand dermatitis (CHD) has been advanced with the introduction of alitretinoin (9-cis-retinoic acid). Although clinical trial data demonstrated the efficacy and safety of alitretinoin, real-world experience is lacking in a more generalized patient population.. Patients with CHD often, and unsuccessfully, attempt several therapeutic options before seeing a dermatologist. This chart review study aimed to examine the experience of using alitretinoin for CHD in a dermatology office setting.. A retrospective chart review of electronic medical records was conducted of all patients prescribed alitretinoin in a community dermatology practice.. Alitretinoin was well tolerated in this patient population of 53 patients and showed a clinically significant reduction in disease symptoms.. Alitretinoin was a safe and well-tolerated treatment with significant clinical improvement in our patient population. Few clinically significant laboratory abnormalities were identified, and only one patient discontinued therapy due to adverse events.

Topics: Adult; Aged; Alitretinoin; Chronic Disease; Community Health Services; Dermatologic Agents; Dermatology; Female; Hand Dermatoses; Humans; Male; Middle Aged; Retreatment; Retrospective Studies; Treatment Outcome; Tretinoin

This non-interventional observational open study (TOCCATA, sponsored by Basilea Pharmaceutica Germany) investigated the use of alitretinoin to treat chronic hand eczema under daily "real life" medical practice conditions in Germany. A total of 349 dermatologists through-out Germany enrolled 680 adult patients with chronic hand eczema. Patients were prescribed and treated with alitretinoin in accordance with the summary of product characteristics. The maximum observation duration was 24 weeks, with efficacy and safety parameters evaluated every 4 weeks. Efficacy was primarily evaluated by assessing disease severity according to the Physician Global Assessment. In total, 56.7% of patients achieved a Physician Global Assessment rating of "clear" or "almost clear" hands, with only small differences in patients with different morphological forms: hyperkeratotic-rhagadiform (59.2%), fingertip (52.2%) and vesicular (47.9%). This observational study demonstrates the effectiveness and tolerability of alitretinoin in everyday clinical practice in addition to the known efficacy and safety obtain-ed by randomized controlled clinical trials.

Topics: Adult; Alitretinoin; Chronic Disease; Eczema; Female; Hand Dermatoses; Humans; Keratolytic Agents; Male; Middle Aged; Severity of Illness Index; Tretinoin

  In a previous large trial (Benefit of Alitretinoin in Chronic Hand Eczema; BACH), 47.7% of patients with severe chronic hand eczema (CHE) who received alitretinoin 30 mg achieved 'clear' or 'almost clear' hands during the initial 24-week treatment course..   The current open-label trial was designed to study extended treatment with a further 12- to 24-week course of oral alitretinoin 30 mg in patients who did not fully respond to initial treatment in the BACH study..   At the end of the BACH study, patients whose eczema was rated 'mild', 'moderate' or 'severe' according to the Physician's Global Assessment (PGA) were eligible for a 24-week, open-label, multicentre study. Patients (n=243) received 30 mg of alitretinoin once daily, irrespective of previous treatment in BACH; either alitretinoin 30 mg, alitretinoin 10 mg or placebo..   By the end of the follow-on study, the PGA response rate to the subsequent course of alitretinoin 30 mg was 50% and 39% in patients treated previously in BACH with 10 or 30 mg per day, respectively, and 51% in patients who previously received placebo in BACH. Alitretinoin was well tolerated, and no significant late-arising toxicities were seen.. For a considerable number of patients with CHE who did not fully respond after an initial 24-week treatment period, a switch from either placebo to the active compound at 30 mg or from the lower to the higher dose, or treatment prolongation at the higher dose could be beneficial. Alitretinoin remains well tolerated for overall treatment durations of up to 48 weeks.

Topics: Administration, Oral; Adult; Alitretinoin; Canada; Chronic Disease; Dermatologic Agents; Eczema; Europe; Female; Hand Dermatoses; Humans; Male; Middle Aged; Retreatment; Tretinoin

Topics: Alitretinoin; Chronic Disease; Eczema; Female; Foot Dermatoses; Humans; Middle Aged; Remission Induction; Tretinoin

Chronic hand eczema (CHE) is a debilitating and distressing disease for patients, the physical symptoms of which are compounded by psychosocial problems. Alitretinoin is an endogenously occurring physiological vitamin A derivative (retinoid) that possesses strong anti-inflammatory and immunomodulatory activity. It is currently the only licensed product for severe CHE unresponsive to treatment with potent topical corticosteroids, and has been proven to be highly effective in clinical trials with two-thirds of patients who responded to treatment remaining in remission at 6 months. For those that did relapse, a second study showed they could be successfully retreated with a further 3-6 month course of alitretinoin. Seven case studies of alitretinoin have been provided by consultant dermatologists showing its use in normal UK clinical practice. The cases chosen demonstrate the efficacy of alitretinoin across several different subtypes of CHE, and the positive effects the treatment brought to patients' quality of life.

Topics: Alitretinoin; Chronic Disease; Dermatologic Agents; Eczema; Hand Dermatoses; Humans; Tretinoin

Topics: Alitretinoin; Chronic Disease; Dermatologic Agents; Female; Foot Dermatoses; Hand Dermatoses; Humans; Middle Aged; Politics; Quality of Life; Tretinoin

Topics: Alitretinoin; Chronic Disease; Dermatologic Agents; Engineering; Hand Dermatoses; Humans; Male; Middle Aged; Tretinoin

Topics: Adult; Alitretinoin; Chronic Disease; Dermatologic Agents; Hand Dermatoses; Humans; Information Science; Male; Tretinoin

Topics: Administration, Oral; Adult; Alitretinoin; Chronic Disease; Dermatitis, Atopic; Dermatologic Agents; Female; Hand Dermatoses; Humans; Male; Middle Aged; Treatment Outcome; Tretinoin; Young Adult

Topics: Alitretinoin; Chronic Disease; Eczema; Hand Dermatoses; Humans; Keratolytic Agents; Tretinoin

Alitretinoin is a new drug for systemic treatment of chronic hand eczema. Previous functional tests of skin topically treated with retinoids have indicated impaired skin barrier function, but no data are available on barrier parameters after systemic alitretinoin treatment. To investigate the effect of systemic alitretinoin on skin barrier function and response to irritants, a secondary objective was to determine if changes occur in the lipid profile of stratum corneum after treatment with systemic alitretinoin. We conducted an open clinical intervention study on eight people ascribed to systemic alitretinoin treatment. The criteria for being ascribed to alitretinoin were chronic hand eczema and insufficient therapeutic response to potent topical corticosteroids. Before initiation and after 2 months of systemic treatment with 30 mg alitretinoin, a challenge with sodium lauryl sulphate (SLS) was performed on the volar forearm and evaluated by trans-epidermal water loss (TEWL), erythema, and a cyanoacrylate skin sample was obtained for lipid analysis. We found no significant changes in response to SLS irritation as evaluated by TEWL and erythema, after treatment with alitretinoin for 2 months. No significant changes in stratum corneum lipids were found after 2 months of treatment. In conclusion, systemic alitretinoin does not influence skin susceptibility to irritants or the ceramide profile of stratum corneum.

Topics: Alitretinoin; Ceramides; Chronic Disease; Disease Progression; Eczema; Epidermis; Erythema; Humans; Irritants; Retinoids; Sodium Dodecyl Sulfate; Tretinoin; Water Loss, Insensible

The impact on patients suffering from chronic hand eczema (CHE) is enormous, as no licensed systemic treatment option with proven efficacy for CHE is available. Alitretinoin is a novel agent which showed high clinical efficacy in patients with severe, refractory CHE. We assessed the cost-effectiveness of alitretinoin for CHE patient treatment from a Swiss third party payer perspective. A further objective of this study was to determine the burden of disease in Switzerland.. A long-term Markov cohort simulation model was used to estimate direct medical costs (euro) and clinical effectiveness (quality adjusted life years, QALYs) of treating severe CHE patients with alitretinoin. Comparison was against the standard treatment of supportive care (optimised emollient therapy). Information on response rates were derived from a randomized controlled clinical trial. Costs were considered from the perspective of the Swiss health system. Swiss epidemiological data was derived from official Swiss Statistic institutions.. Annual costs of alitretinoin treatment accounted for 2'212 euro. After a time horizon of 22.4 years, average remaining long-term costs accounted for 42'208 euro or 38'795 euro in the alitretinoin and the standard treatment arm, respectively. Compared with the standard therapy, the addition of alitretinoin yielded an average gain of 0.230 QALYs at the end of the simulation. Accordingly, the incremental cost-effectiveness ratio resulted in 14'816 euro/QALY gained. These results were robust to changes in key model assumptions.. The therapy for CHE patients is currently insufficient. In our long-term model we identified the treatment with alitretinoin as a cost-effective alternative for the therapy of CHE patients in Switzerland.

Topics: Administration, Oral; Adolescent; Adult; Aged; Alitretinoin; Chronic Disease; Cost of Illness; Cost-Benefit Analysis; Eczema; Humans; Longitudinal Studies; Markov Chains; Middle Aged; Quality-Adjusted Life Years; Severity of Illness Index; Switzerland; Treatment Outcome; Tretinoin; Young Adult

The management of chronic hand eczema is often inadequate. There are currently no evidence-based guidelines specifically for the management of chronic hand eczema, and evidence for established treatments for hand eczema is not of sufficient quality to guide clinical practice. This consensus statement, based on a review of published data and clinical practice in both primary and secondary care, is intended to guide the management of chronic hand eczema. It describes the epidemiology and pathogenesis of hand eczema, its diagnosis and its effect on patients' quality of life. Management strategies include a skin education programme, lifestyle changes, and the use of emollients, barriers and soap substitutes. Topical drug therapy includes topical steroids and calcineurin inhibitors. Treatment with psoralen ultraviolet A and systemic therapies may then be appropriate, although there is no strong evidence of efficacy. Alitretinoin has been shown to be effective in a randomized controlled trial, and is currently the only treatment specifically licensed for the treatment of hand eczema. Recommendations for management are summarized in a treatment algorithm.

Topics: Alitretinoin; Chronic Disease; Dermatologic Agents; Emollients; Glucocorticoids; Hand Dermatoses; Humans; Quality of Life; Referral and Consultation; Tretinoin