Alitretinoin versus phototherapy as the first-line treatment in adults with severe chronic hand eczema: the ALPHA RCT.

IF 3.5 2区 医学 Q1 HEALTH CARE SCIENCES & SERVICES Health technology assessment Pub Date : 2024-10-01 DOI:10.3310/TWQC0141
Miriam Wittmann, Isabelle L Smith, Sarah Tess Brown, Anna Berekméri, Armando Vargas-Palacios, Lesley Sunderland, Amy Barker, Fiona Cowdell, Steven Ersser, Rachael Gilberts, Cathy Green, Philip Hampton, Catherine Smith, Jane Nixon
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There is no treatment pathway generally accepted by UK dermatologists.</p><p><strong>Primary objective: </strong>Compare alitretinoin and ultraviolet therapy as first-line therapy in terms of disease activity at 12 weeks post planned start of treatment.</p><p><strong>Design: </strong>Prospective, multicentre, open-label, two-arm parallel group, adaptive randomised controlled trial with one planned interim analysis, and an economic evaluation.</p><p><strong>Setting: </strong>UK secondary care dermatology outpatient clinics.</p><p><strong>Participants: </strong>Patients with severe chronic hand eczema unresponsive to at least 4 weeks of treatment with potent topical corticosteroids.</p><p><strong>Primary end point: </strong>Natural logarithm of the Hand Eczema Severity Index + 1, 12 weeks post planned start of treatment.</p><p><strong>Randomisation: </strong>Participants randomised 1 : 1 by minimisation to alitretinoin or ultraviolet therapy for 12 to 24 weeks.</p><p><strong>Blinding: </strong>Blinded primary end-point assessor.</p><p><strong>Results: </strong>Intention-to-treat population: 441 (100.0%) participants; 220 (49.9%) alitretinoin and 221 (50.1%) ultraviolet therapy. 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Abstract

Background: Hand eczema is common and a cause of morbidity and occupational disability. When education, irritant/contact allergen avoidance, moisturisation and topical corticosteroids are insufficient to control chronic hand eczema, ultraviolet therapy or systemic immune-modifying drugs are used. There is no treatment pathway generally accepted by UK dermatologists.

Primary objective: Compare alitretinoin and ultraviolet therapy as first-line therapy in terms of disease activity at 12 weeks post planned start of treatment.

Design: Prospective, multicentre, open-label, two-arm parallel group, adaptive randomised controlled trial with one planned interim analysis, and an economic evaluation.

Setting: UK secondary care dermatology outpatient clinics.

Participants: Patients with severe chronic hand eczema unresponsive to at least 4 weeks of treatment with potent topical corticosteroids.

Primary end point: Natural logarithm of the Hand Eczema Severity Index + 1, 12 weeks post planned start of treatment.

Randomisation: Participants randomised 1 : 1 by minimisation to alitretinoin or ultraviolet therapy for 12 to 24 weeks.

Blinding: Blinded primary end-point assessor.

Results: Intention-to-treat population: 441 (100.0%) participants; 220 (49.9%) alitretinoin and 221 (50.1%) ultraviolet therapy. At least one dose was received by 212 (96.4%) alitretinoin and 196 (88.7%) ultraviolet therapy participants.

Primary outcome: The unadjusted median (interquartile range) relative change in hand eczema severity index at 12 weeks was 30% (10-70%) of that at baseline for alitretinoin compared with 50% (20-100%) for ultraviolet therapy. There was a statistically significant benefit of alitretinoin compared with ultraviolet therapy at 12 weeks, with an estimated fold change or relative difference (95% confidence interval) = 0.66 (0.52 to 0.82), p = 0.0003 at 12 weeks. There was no evidence of a difference at 24 or 52 weeks, with the estimated fold change (95% confidence interval) equal to 0.92 (0.798 to 1.08) and 1.27 (0.97 to 1.67), respectively.

Primary analysis results were consistent for secondary end points: Fifty-nine per cent allocated to alitretinoin and 61% allocated to ultraviolet therapy achieved a clear/almost clear assessment during the trial period. Differential treatment compliance observed: 145 (65.9%) alitretinoin and 53 (24.0%) ultraviolet therapy participants confirmed compliance (≥ 80% received, no treatment breaks > 7 days during first 12 weeks). High levels of missing data were observed.

Safety: One hundred and thirty-five reportable adverse events across 79 participants, 55 (25.0%) alitretinoin and 24 (10.9%) ultraviolet therapy. Four serious adverse events (two alitretinoin, two ultraviolet therapy). Four pregnancies reported (three alitretinoin, one ultraviolet therapy). No new safety signals were detected.

Conclusion: As a first-line therapy, alitretinoin showed more rapid improvement and superiority to ultraviolet therapy at week 12. This difference was not observed at later time points. Alitretinoin is cost-effective at weeks 12 and 52. Ultraviolet therapy is cost-effective after 10 years, with a high degree of uncertainty. Hand eczema severity index may be a useful primary outcome measure for hand eczema trials; ALPHA results will inform future trials.

Limitations: Treatment compliance was poor for ultraviolet therapy. Regular twice weekly treatment was not received by most patients. Assessment of long-term effects of randomised treatments was complicated by use of second-line treatments post treatment phase.

Further work: Further analysis of substudies and pilot data will provide valuable information for future studies. A clear need for better therapeutic approaches for severe chronic hand eczema remains. Future studies will need to further address long-term benefits of treatments given.

Trial registration: This trial is registered as ISRCTN80206075.

Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 12/186/01) and is published in full in Health Technology Assessment; Vol. 28, No. 59. See the NIHR Funding and Awards website for further award information.

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成人严重慢性手部湿疹的一线治疗方法:阿立替诺与光疗:ALPHA RCT。
背景:手部湿疹很常见,是导致发病和职业残疾的原因之一。当教育、避免刺激性/接触性过敏原、保湿和外用皮质类固醇激素不足以控制慢性手部湿疹时,就会使用紫外线疗法或全身性免疫调节药物。英国皮肤科医生没有普遍接受的治疗途径:比较阿维A酸和紫外线疗法作为一线疗法在计划开始治疗 12 周后的疾病活动情况:设计:前瞻性、多中心、开放标签、双臂平行组、适应性随机对照试验,计划进行一次中期分析和一项经济评估:参与者:严重慢性手部湿疹患者:对强效外用皮质类固醇激素治疗至少 4 周无效的严重慢性手部湿疹患者:手部湿疹严重程度指数自然对数+1,计划开始治疗后12周:参与者按1:1的比例随机接受阿维A酸或紫外线治疗,疗程为12至24周:盲法:主要终点评估者盲法:意向治疗人群441人(100.0%)接受治疗;220人(49.9%)接受阿维A酸治疗,221人(50.1%)接受紫外线治疗。212名(96.4%)阿立替诺患者和196名(88.7%)紫外线治疗患者至少接受了一次治疗:阿维A酸治疗12周时手部湿疹严重程度指数的未调整中位数(四分位间范围)相对变化为基线值的30%(10-70%),而紫外线治疗为50%(20-100%)。与紫外线疗法相比,阿维A酸在12周时的疗效具有统计学意义,12周时的估计折叠变化或相对差异(95%置信区间)=0.66(0.52至0.82),p=0.0003。没有证据表明 24 周或 52 周时存在差异,估计折叠变化(95% 置信区间)分别为 0.92(0.798 至 1.08)和 1.27(0.97 至 1.67):在试验期间,59%接受阿维A酸治疗的患者和61%接受紫外线治疗的患者的评估结果为 "清晰/基本清晰"。观察到不同的治疗依从性:145名(65.9%)阿立替诺参与者和53名(24.0%)紫外线疗法参与者确认了治疗依从性(接受治疗的比例≥80%,前12周内治疗中断时间未超过7天)。数据缺失率较高:79名参与者发生了135起应报告的不良事件,其中55起(25.0%)为阿立替诺,24起(10.9%)为紫外线疗法。四例严重不良事件(两例阿利曲汀,两例紫外线疗法)。四例怀孕报告(三例阿维A酸,一例紫外线疗法)。未发现新的安全信号:结论:作为一线疗法,阿利替诺在第12周时显示出比紫外线疗法更快的改善和更好的疗效。结论:作为一线疗法,阿利替诺在第 12 周时显示出更快的改善速度和优于紫外线疗法的疗效,但在随后的时间点则未观察到这种差异。阿利替诺在第 12 周和第 52 周具有成本效益。紫外线疗法在 10 年后具有成本效益,但不确定性很高。手部湿疹严重程度指数可能是手部湿疹试验的一个有用的主要结果测量指标;ALPHA的结果将为未来的试验提供参考:局限性:紫外线疗法的治疗依从性较差。大多数患者没有接受每周两次的定期治疗。由于在治疗阶段后使用了二线疗法,因此评估随机疗法的长期效果变得复杂:进一步的工作:对子研究和试验数据的进一步分析将为今后的研究提供有价值的信息。对于严重的慢性手部湿疹,显然仍需要更好的治疗方法。未来的研究将需要进一步探讨治疗的长期益处:该试验的注册号为 ISRCTN80206075:该奖项由美国国家健康与护理研究所(NIHR)健康技术评估项目资助(NIHR奖项编号:12/186/01),全文发表于《健康技术评估》第28卷第59期。更多奖项信息请参阅 NIHR Funding and Awards 网站。
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来源期刊
Health technology assessment
Health technology assessment 医学-卫生保健
CiteScore
6.90
自引率
0.00%
发文量
94
审稿时长
>12 weeks
期刊介绍: Health Technology Assessment (HTA) publishes research information on the effectiveness, costs and broader impact of health technologies for those who use, manage and provide care in the NHS.
期刊最新文献
Early high-dose cryoprecipitate to reduce mortality in adult patients with traumatic haemorrhage: the CRYOSTAT-2 RCT with cost-effectiveness analysis. Diagnostic accuracy of point-of-care tests for acute respiratory infection: a systematic review of reviews. The effect of two speech and language approaches on speech problems in people with Parkinson's disease: the PD COMM RCT. Alitretinoin versus phototherapy as the first-line treatment in adults with severe chronic hand eczema: the ALPHA RCT. Transperineal biopsy devices in people with suspected prostate cancer - a systematic review and economic evaluation.
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