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Mark Sculpher – One of the best experts on this subject based on the ideXlab platform.

  • Alitretinoina nell’eczema cronico grave alle mani. Valutazione di tecnologia singola presso il NICE
    PharmacoEconomics Italian Research Articles, 2011
    Co-Authors: Mark Rodgers, Susan Griffin, Mike Paulden, Russell Slack, John R. Ingram, Nerys Woolacott, Steve Duffy, Mark Sculpher

    Abstract:

    The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of Alitretinoin (Basilea Pharmaceuticals Ltd, Basel, Switzerland) to submit evidence for the clinical and cost effectiveness of this drug for the treatment of patients with severe chronic hand eczema (CHE), as part of the Institute’s single technology appraisal (STA) process. The Centre for Reviews and Dissemination and the Centre for Health Economics at the University of York were commissioned to act as the Evidence Review Group (ERG). This article provides a description of the company submission, the ERG review and NICE’s subsequent decisions. The ERG produced a critical review of the evidence for the clinical and cost effectiveness of the technology based upon the manufacturer’s submission to NICE. The ERG also independently searched for relevant evidence and modified the manufacturer’s decision analytic model to examine the impact of altering some of the key assumptions. The main clinical effectiveness data were derived from a single-placebo randomized controlled trial (RCT) of daily treatment with Alitretinoin for 12–24 weeks, with follow-up for a further 24 weeks, in patients with severe CHE unresponsive to topical corticosteroids. A significantly greater proportion of patients achieved ‘clear’ or ‘almost clear’ hands by week 24 with Alitretinoin than those using placebo: 48% with Alitretinoin 30 mg (p < 0.001); 28% with Alitretinoin 10 mg (p < 0.005); 17% with placebo. Most patients who responded remained in remission during the 24-week follow-up period. The most commonly reported adverse event was dose-dependent headache, with rates of 20% in the Alitretinoin 30 mg group and 11 % in the Alitretinoin 10 mg group, respectively. Serious adverse events were rare, although Alitretinoin was associated with increases in both total cholesterol and triglycerides. No direct or indirect comparisons of Alitretinoin with any of the relevant treatment comparators (psoralen + UVA [PUVA], ciclosporin or azathioprine) were available. In the manufacturer’s original submission to NICE, the base-case incremental cost-effectiveness ratios (ICERs) reported for Alitretinoin were £8614 per QALY versus ciclosporin, -£469 per QALY versus PUVA (with Alitretinoin dominant) and £10 612 per QALY versus azathioprine (year 2007–8 values). In response to a request from the ERG, the manufacturers provided a revised model that compared Alitretinoin only with placebo, for which the ICER was reported to be £12 931. However, the omission of adverse events entirely from this revised model, in combination with a number of other factors, led the ERG to conclude that the model underestimated the costs of treatment associated with Alitretinoin. Estimates of health-related quality of life (HR-QOL) were the primary source of uncertainty, with the use of values from an alternative source producing ICERs of around £30 000 per QALY gained. The ERG concluded that, although the evidence presented indicates that Alitretinoin is efficacious in the treatment of severe CHE, it gives little indication of Alitretinoin’s efficacy relative to likely alternative treatment options or its efficacy and safety in the longer term. Although the ICERs estimated by the manufacturer suggested that Alitretinoin may be cost effective for use in the UK NHS, utilizing the alternative HR-QOL estimates resulted in a 2-fold increase in the ICER. Thus, there was considerable uncertainty as to the true ICER of Alitretinoin versus the relevant treatment comparators. TheAppraisal Committee recommended that Alitretinoin be provided to those patients with severe CHE and a Dermatology Life Quality Index (DLQI) score of at least 15. They recommended that treatment be stopped as soon as an adequate response was observed, or if CHE remained severe at 12 weeks, or if response was inadequate at 24 weeks.

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  • Alitretinoin for Severe Chronic Hand Eczema
    PharmacoEconomics, 2010
    Co-Authors: Mark Rodgers, Susan Griffin, Mike Paulden, Russell Slack, Steven Duffy, John R. Ingram, Nerys Woolacott, Mark Sculpher

    Abstract:

    The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of Alitretinoin (Basilea Pharmaceuticals Ltd, Basel, Switzerland) to submit evidence for the clinical and cost effectiveness of this drug for the treatment of patients with severe chronic hand eczema (CHE), as part of the Institute’s single technology appraisal (STA) process. The Centre for Reviews and Dissemination and the Centre for Health Economics at the University of York were commissioned to act as the Evidence Review Group (ERG). This article provides a description of the company submission, the ERG review and NICE’s subsequent decisions. The ERG produced a critical review of the evidence for the clinical and cost effectiveness of the technology based upon the manufacturer’s submission to NICE. The ERG also independently searched for relevant evidence and modified the manufacturer’s decision analytic model to examine the impact of altering some of the key assumptions. The main clinical effectiveness data were derived from a single-placebo randomized controlled trial (RCT) of daily treatment with Alitretinoin for 12–24 weeks, with follow-up for a further 24 weeks, in patients with severe CHE unresponsive to topical corticosteroids. A significantly greater proportion of patients achieved ‘clear’ or ‘almost clear’ hands by week 24 with Alitretinoin than those using placebo: 48% with Alitretinoin 30mg (p < 0.001); 28% with Alitretinoin 10 mg (p < 0.005); 17% with placebo. Most patients who responded remained in remission during the 24-week follow-up period. The most commonly reported adverse event was dose-dependent headache, with rates of 20% in the Alitretinoin 30 mg group and 11% in the Alitretinoin 10mg group, respectively. Serious adverse events were rare, although Alitretinoin was associated with increases in both total cholesterol and triglycerides. No direct or indirect comparisons of Alitretinoin with any of the relevant treatment comparators (psoralen +UVA [PUVA], ciclosporin or azathioprine) were available. In the manufacturer’s original submission to NICE, the base-case incremental cost-effectiveness ratios (ICERs) reported for Alitretinoin were £8614 per QALY versus ciclosporin, −£469 per QALY versus PUVA (with Alitretinoin dominant) and £10 612 per QALY versus azathioprine (year 2007–8 values). In response to a request from the ERG, the manufacturers provided a revised model that compared Alitretinoin only with placebo, for which the ICER was reported to be £12 931. However, the omission of adverse events entirely from this revised model, in combination with a number of other factors, led the ERG to conclude that the model underestimated the costs of treatment associated with Alitretinoin. Estimates of health-related quality of life (HR-QOL) were the primary source of uncertainty, with the use of values from an alternative source producing ICERs of around £30 000 per QALY gained. The ERG concluded that, although the evidence presented indicates that Alitretinoin is efficacious in the treatment of severe CHE, it gives little indication of Alitretinoin’s efficacy relative to likely alternative treatment options or its efficacy and safety in the longer term. Although the ICERs estimated by the manufacturer suggested that Alitretinoin may be cost effective for use in the UK NHS, utilizing the alternative HR-QOL estimates resulted in a 2-fold increase in the ICER. Thus, there was considerable uncertainty as to the true ICER of Alitretinoin versus the relevant treatment comparators. The Appraisal Committee recommended that Alitretinoin be provided to those patients with severe CHE and a Dermatology Life Quality Index (DLQI) score of at least 15. They recommended that treatment be stopped as soon as an adequate response was observed, or if CHE remained severe at 12 weeks, or if response was inadequate at 24 weeks.

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  • Alitretinoin for the treatment of severe chronic hand eczema.
    Health technology assessment (Winchester England), 2010
    Co-Authors: Mike Paulden, Mark Rodgers, Susan Griffin, Russell Slack, Steven Duffy, John R. Ingram, Nerys Woolacott, Mark Sculpher

    Abstract:

    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 supportive care (placebo). However, the model underestimates the costs of treatment associated with Alitretinoin. The manufacturer assumed that patients receiving Alitretinoin visited the dermatologist every 4 weeks and ceased treatment as soon as they responded to it. If, in practice, patients would receive treatment for longer than this, then the manufacturer’s model will have significantly underestimated the costs to the NHS. Additional analyses undertaken by the ERG produced ICERs close to 30,000 pounds per QALY gained for Alitretinoin versus supportive care. This was largely due to uncertainty surrounding the impact of Alitretinoin on HRQoL. The placebo-controlled trials conducted to date have established that Alitretinoin can be efficacious for the treatment of severe CHE refractory to topical steroids, but longer term follow-up of trials or the implementation of registries is required to better establish the longer term efficacy or safety of Alitretinoin. NICE recommended the use of Alitretinoin for patients with severe CHE and a Dermatology Life Quality Index (DLQI) score of at least 15. Treatment was recommended to be stopped as soon as an adequate response was observed, or if CHE remained severe at 12 weeks, or if response was inadequate at 24 weeks.

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J Maares – One of the best experts on this subject based on the ideXlab platform.

  • Extended treatment with oral Alitretinoin for patients with chronic hand eczema not fully responding to initial treatment
    Clinical and Experimental Dermatology, 2012
    Co-Authors: Charles Lynde, T C Brown, Frederic Cambazard, T Ruzicka, M. Sebastian, J Maares

    Abstract:

    Summary

    Background.  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.

    Objectives.  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.

    Methods.  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.

    Results.  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.

    Conclusions.  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.

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  • Pharmacokinetics, efficacy and safety of Alitretinoin in moderate or severe chronic hand eczema
    Clinical and Experimental Dermatology, 2011
    Co-Authors: A. H. Schmitt-hoffmann, Pieter-jan Coenraads, B. Roos, J. Van De Wetering, J Sauer, J Spickermann, K. Stoeckel, D. Edwards, J Maares

    Abstract:

    P>Background. Recent studies have found that Alitretinoin can induce clinically significant responses in subjects with severe chronic hand eczema (CHE) unresponsive to topical corticosteroids. Aims. To assess the pharmacokinetics (PK), efficacy and safety of Alitretinoin 10 or 30 mg once daily. Methods. 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. Results. 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. Conclusions. 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.

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  • Pharmacokinetic interactions between Alitretinoin and ketoconazole or simvastatin or ciclosporin A.
    Clinical and Experimental Dermatology, 2011
    Co-Authors: A. H. Schmitt-hoffmann, B. Roos, A. Schoetzau, J Sauer, J Spickermann, J Maares, I Meyer

    Abstract:

    Summary

    Background.  Based on in vitro data with isolated cytochrome P450 (CYP) isoenzymes, Alitretinoin interacts only with CYP3A4, and the potential for drug–drug interactions is considered negligible.

    Aim.  To confirm in humans the lack of potential interactions between CYP3A4 and Alitretinoin in vivo.

    Methods.  This was a multiple-dose, open-label, parallel-group, single-centre study, which enrolled 54 healthy male volunteers aged 18–45 years. Subjects were divided into three groups, with 18 in each group: group 1 received either Alitretinoin 30 mg and ketoconazole 200 mg, group 2 Alitretinoin 30 mg and simvastatin 40 mg, and group 3 Alitretinoin 30 mg and ciclosporin A 300-mg.

    Results.  At the highest therapeutic dose of 30 mg, Alitretinoin had no significant effect on the pharmacokinetics (PK) of ketoconazole and ciclosporin A. There was a significant but not clinically relevant effect of simvastatin on the area under the curve (AUC) of plasma concentration vs. time and on maximum plasma concentration (Cmax) after repeated administration of Alitretinoin. Exposure to simvastatin concomitantly with Alitretinoin was decreased by 16% for AUC and 23% for Cmax. The CYP3A4 ± PgP substrates of simvastatin and ciclosporin A did not affect the single or repeated dose PK of Alitretinoin. The strong CYP3A4/PgP inhibitor ketoconazole led to significant increases in both AUC and Cmax values for Alitretinoin.

    Conclusions.  Single and repeated doses of Alitretinoin do not alter the PK of ciclosporin A and ketoconazole. Simvastatin levels were slightly but significantly reduced by co-administration of Alitretinoin. Substrates of CYP3A4 did not affect the PK of Alitretinoin. However, ketoconazole significantly increased the plasma levels of Alitretinoin, therefore, co-administration with CYP3A4 inhibitors such as ketoconazole may require a dose reduction of Alitretinoin.

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Mark Rodgers – One of the best experts on this subject based on the ideXlab platform.

  • Alitretinoina nell’eczema cronico grave alle mani. Valutazione di tecnologia singola presso il NICE
    PharmacoEconomics Italian Research Articles, 2011
    Co-Authors: Mark Rodgers, Susan Griffin, Mike Paulden, Russell Slack, John R. Ingram, Nerys Woolacott, Steve Duffy, Mark Sculpher

    Abstract:

    The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of Alitretinoin (Basilea Pharmaceuticals Ltd, Basel, Switzerland) to submit evidence for the clinical and cost effectiveness of this drug for the treatment of patients with severe chronic hand eczema (CHE), as part of the Institute’s single technology appraisal (STA) process. The Centre for Reviews and Dissemination and the Centre for Health Economics at the University of York were commissioned to act as the Evidence Review Group (ERG). This article provides a description of the company submission, the ERG review and NICE’s subsequent decisions. The ERG produced a critical review of the evidence for the clinical and cost effectiveness of the technology based upon the manufacturer’s submission to NICE. The ERG also independently searched for relevant evidence and modified the manufacturer’s decision analytic model to examine the impact of altering some of the key assumptions. The main clinical effectiveness data were derived from a single-placebo randomized controlled trial (RCT) of daily treatment with Alitretinoin for 12–24 weeks, with follow-up for a further 24 weeks, in patients with severe CHE unresponsive to topical corticosteroids. A significantly greater proportion of patients achieved ‘clear’ or ‘almost clear’ hands by week 24 with Alitretinoin than those using placebo: 48% with Alitretinoin 30 mg (p < 0.001); 28% with Alitretinoin 10 mg (p < 0.005); 17% with placebo. Most patients who responded remained in remission during the 24-week follow-up period. The most commonly reported adverse event was dose-dependent headache, with rates of 20% in the Alitretinoin 30 mg group and 11 % in the Alitretinoin 10 mg group, respectively. Serious adverse events were rare, although Alitretinoin was associated with increases in both total cholesterol and triglycerides. No direct or indirect comparisons of Alitretinoin with any of the relevant treatment comparators (psoralen + UVA [PUVA], ciclosporin or azathioprine) were available. In the manufacturer’s original submission to NICE, the base-case incremental cost-effectiveness ratios (ICERs) reported for Alitretinoin were £8614 per QALY versus ciclosporin, -£469 per QALY versus PUVA (with Alitretinoin dominant) and £10 612 per QALY versus azathioprine (year 2007–8 values). In response to a request from the ERG, the manufacturers provided a revised model that compared Alitretinoin only with placebo, for which the ICER was reported to be £12 931. However, the omission of adverse events entirely from this revised model, in combination with a number of other factors, led the ERG to conclude that the model underestimated the costs of treatment associated with Alitretinoin. Estimates of health-related quality of life (HR-QOL) were the primary source of uncertainty, with the use of values from an alternative source producing ICERs of around £30 000 per QALY gained. The ERG concluded that, although the evidence presented indicates that Alitretinoin is efficacious in the treatment of severe CHE, it gives little indication of Alitretinoin’s efficacy relative to likely alternative treatment options or its efficacy and safety in the longer term. Although the ICERs estimated by the manufacturer suggested that Alitretinoin may be cost effective for use in the UK NHS, utilizing the alternative HR-QOL estimates resulted in a 2-fold increase in the ICER. Thus, there was considerable uncertainty as to the true ICER of Alitretinoin versus the relevant treatment comparators. TheAppraisal Committee recommended that Alitretinoin be provided to those patients with severe CHE and a Dermatology Life Quality Index (DLQI) score of at least 15. They recommended that treatment be stopped as soon as an adequate response was observed, or if CHE remained severe at 12 weeks, or if response was inadequate at 24 weeks.

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  • Alitretinoin for Severe Chronic Hand Eczema
    PharmacoEconomics, 2010
    Co-Authors: Mark Rodgers, Susan Griffin, Mike Paulden, Russell Slack, Steven Duffy, John R. Ingram, Nerys Woolacott, Mark Sculpher

    Abstract:

    The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of Alitretinoin (Basilea Pharmaceuticals Ltd, Basel, Switzerland) to submit evidence for the clinical and cost effectiveness of this drug for the treatment of patients with severe chronic hand eczema (CHE), as part of the Institute’s single technology appraisal (STA) process. The Centre for Reviews and Dissemination and the Centre for Health Economics at the University of York were commissioned to act as the Evidence Review Group (ERG). This article provides a description of the company submission, the ERG review and NICE’s subsequent decisions. The ERG produced a critical review of the evidence for the clinical and cost effectiveness of the technology based upon the manufacturer’s submission to NICE. The ERG also independently searched for relevant evidence and modified the manufacturer’s decision analytic model to examine the impact of altering some of the key assumptions. The main clinical effectiveness data were derived from a single-placebo randomized controlled trial (RCT) of daily treatment with Alitretinoin for 12–24 weeks, with follow-up for a further 24 weeks, in patients with severe CHE unresponsive to topical corticosteroids. A significantly greater proportion of patients achieved ‘clear’ or ‘almost clear’ hands by week 24 with Alitretinoin than those using placebo: 48% with Alitretinoin 30mg (p < 0.001); 28% with Alitretinoin 10 mg (p < 0.005); 17% with placebo. Most patients who responded remained in remission during the 24-week follow-up period. The most commonly reported adverse event was dose-dependent headache, with rates of 20% in the Alitretinoin 30 mg group and 11% in the Alitretinoin 10mg group, respectively. Serious adverse events were rare, although Alitretinoin was associated with increases in both total cholesterol and triglycerides. No direct or indirect comparisons of Alitretinoin with any of the relevant treatment comparators (psoralen +UVA [PUVA], ciclosporin or azathioprine) were available. In the manufacturer’s original submission to NICE, the base-case incremental cost-effectiveness ratios (ICERs) reported for Alitretinoin were £8614 per QALY versus ciclosporin, −£469 per QALY versus PUVA (with Alitretinoin dominant) and £10 612 per QALY versus azathioprine (year 2007–8 values). In response to a request from the ERG, the manufacturers provided a revised model that compared Alitretinoin only with placebo, for which the ICER was reported to be £12 931. However, the omission of adverse events entirely from this revised model, in combination with a number of other factors, led the ERG to conclude that the model underestimated the costs of treatment associated with Alitretinoin. Estimates of health-related quality of life (HR-QOL) were the primary source of uncertainty, with the use of values from an alternative source producing ICERs of around £30 000 per QALY gained. The ERG concluded that, although the evidence presented indicates that Alitretinoin is efficacious in the treatment of severe CHE, it gives little indication of Alitretinoin’s efficacy relative to likely alternative treatment options or its efficacy and safety in the longer term. Although the ICERs estimated by the manufacturer suggested that Alitretinoin may be cost effective for use in the UK NHS, utilizing the alternative HR-QOL estimates resulted in a 2-fold increase in the ICER. Thus, there was considerable uncertainty as to the true ICER of Alitretinoin versus the relevant treatment comparators. The Appraisal Committee recommended that Alitretinoin be provided to those patients with severe CHE and a Dermatology Life Quality Index (DLQI) score of at least 15. They recommended that treatment be stopped as soon as an adequate response was observed, or if CHE remained severe at 12 weeks, or if response was inadequate at 24 weeks.

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  • Alitretinoin for the treatment of severe chronic hand eczema.
    Health technology assessment (Winchester England), 2010
    Co-Authors: Mike Paulden, Mark Rodgers, Susan Griffin, Russell Slack, Steven Duffy, John R. Ingram, Nerys Woolacott, Mark Sculpher

    Abstract:

    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 supportive care (placebo). However, the model underestimates the costs of treatment associated with Alitretinoin. The manufacturer assumed that patients receiving Alitretinoin visited the dermatologist every 4 weeks and ceased treatment as soon as they responded to it. If, in practice, patients would receive treatment for longer than this, then the manufacturer’s model will have significantly underestimated the costs to the NHS. Additional analyses undertaken by the ERG produced ICERs close to 30,000 pounds per QALY gained for Alitretinoin versus supportive care. This was largely due to uncertainty surrounding the impact of Alitretinoin on HRQoL. The placebo-controlled trials conducted to date have established that Alitretinoin can be efficacious for the treatment of severe CHE refractory to topical steroids, but longer term follow-up of trials or the implementation of registries is required to better establish the longer term efficacy or safety of Alitretinoin. NICE recommended the use of Alitretinoin for patients with severe CHE and a Dermatology Life Quality Index (DLQI) score of at least 15. Treatment was recommended to be stopped as soon as an adequate response was observed, or if CHE remained severe at 12 weeks, or if response was inadequate at 24 weeks.

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