006 Comparison of alitretinoin vs. psoralen plus ultraviolet A as first-line treatments for chronic severe hand eczema: results from the ALPHA trial

Abstract

Abstract Severe chronic hand eczema resistant to topical corticosteroid treatment is an important cause of morbidity and occupational disability. There is uncertainty regarding the best treatment approach and currently no treatment pathway is generally accepted by UK dermatologists. The primary aim of the ALPHA trial was to compare alitretinoin and immersion psoralen plus ultraviolet A (PUVA) as a first-line therapy in terms of disease activity at 12 weeks after the planned start of treatment. We conducted a prospective, multicentre, open-label, two-arm parallel group, adaptive randomized controlled trial. The natural logarithm of the Hand Eczema Severity Index (HECSI) + 1 at 12 weeks after the planned start of treatment was chosen as the primary endpoint so the relative effect of treatment could be estimated. In total, 514 participants were required to detect a fold change of 1.3 (5% two-sided significance level, 80% power, 20% attrition). Participants were randomized 1 : 1 by minimization to alitretinoin or immersion PUVA for 12–24 weeks. The intention-to-treat population consisted of 441 participants: 220 (49.9%) allocated to alitretinoin and 221 (50.1%) to immersion PUVA. In total, 212 (96.4%) alitretinoin participants and 196 (88.7%) immersion PUVA participants received at least one dose. There was a statistically significant benefit of alitretinoin compared with immersion PUVA at 12 weeks, with an estimated fold change of 0.66 [95% confidence interval (CI) 0.52–0.82; P < 0.001]. There was no evidence of a difference at 24 or 52 weeks. Of those allocated to alitretinoin and immersion PUVA, 59% and 61%, respectively, were observed to achieve a clear/almost clear assessment during the trial period. Alitretinoin was more cost-effective than immersion PUVA. Limitations include differences in treatment compliance and differential missing data levels. In total, 145 (65.9%) alitretinoin participants and 53 (24.0%) immersion PUVA participants were observed to comply (≥ 80% received and no treatment breaks of > 7 days during first 12 weeks). Thus, twice-weekly attendance for PUVA was not received by most participants. However, this represents standard of care with ALPHA run as a pragmatic trial using standard-of-care settings for the interventions. A further limitation was that assessment of long-term effects of randomized treatments was complicated by permitted use of second-line treatments after the treatment phase; therefore, trial conclusions are for randomized treatments as first-line therapies. We conclude that, as a first-line therapy, patients on alitretinoin showed more rapid improvement and superiority than those treated with immersion PUVA at week 12, but this difference was not observed at later time points. Future studies will need to further address the long-term benefits of treatments given and complex treatment pathways.