ALPHA Study Finds Alitretinoin Is Fast, Effective for CHE Treatment

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In a recent ALPHA clinical trial, investigators found that alitretinoin is better at reducing symptoms of CHE after 23 weeks, when compared to ultraviolet phototherapy.¹ Overall, the researchers found that both treatments led to CHE reductions but alitretinoin showed more rapid improvement and superiority to UV therapy at week 12. The study also analyzed other factors that contribute to the choice between the 2 treatment methods such as cost-effectiveness, relapse time, and quality of life. 

The phase 3, multicenter, open-label study (ISRCTN80206075) was conducted in 31 outpatient clinics in England, Scotland, and Wales between October 2015 and June 2021. Participants (N=441) had severe unresponsive CHE, despite at least 4 weeks of topical corticosteroid treatment. The majority of patients (61.9%) were female and of white ethnicity (88.9%); the mean age was 46 years. A majority (70%) of patients had been suffering with CHE for more than 2 years.

The two-arm trial consisted of 12 to 24 weeks of treatment; length of treatment was determined on a case-by-case basis determined by response.Participants were randomly assigned to alitretinoin, 30 mg taken once a day (N=220), and phototherapy, twice a week at a hospital (N=221).Patients could seek different treatments after the trial; the researchers collected information on their CHE symptoms for up to 1 year. 

After 12 weeks, severe hand eczema symptoms improved for both groups of patients but improved most for those that took alitretinoin, with an estimated fold change of 0.66 (0.52, 0.82), p = 0.0003.With alitretinoin, 27.6% of patients were clear or almost clear while 23.6% of patients using UV therapy had the same results. Both groups had a lower median HECSI score. However, at 24 weeks and 1 year after joining the trial, there was no evidence of a difference between alitretinoin and phototherapy as a first-line treatment.

In terms of secondary end points, there was no evidence of a difference in terms of the Patient Benefit Index for Hand Eczema or Dermatology Life Quality Index.Overall, alitretinoin was more cost-effective at weeks 12 and 15. However, there are some results that predict UV therapy is more cost-effective in a long-term span of 10 years, but this probability is still uncertain.

In terms of safety, 79 participants had adverse effects, 55 of whom were treated with alitretinoin and 24 who had been treated with UV therapy. Only 4 of these were reported as serious (2 in the alitretinoin group and 2 in the phototherapy group).

There were some study limitations because more patients stopped UV therapy early compared to those who received alitretinoin. Due to difficulty scheduling and other conflicting factors, regular compliance twice a week was not achieved by most participants. Investigators are unsure if those who were treated with phototherapy received the adequate dosage, which could influence results.

“Alitretinoin provides a convenient, instant relief or a ‘quick fix’ for patients with severe hand eczema,” the authors concluded. “Alitretinoin is more convenient for lots of people, but it is important to have other options available for people who would prefer not to, or are unable to, take alitretinoin.”

Alitretinoin, a systemic pill, and UV therapy, in which hands are covered with psoralen and placed under UV light, are the 2 treatments most often used by dermatologists in the United Kingdom. Clear treatment guidelines and therapeutic approaches for CHE are still lacking and more evidence is needed to determine which method is most efficient.² Future studies will need to further address the long-term benefits of treatments given.

“Long-term control of severe hand eczema is important,” the authors wrote. “Individual discussions on the pros and cons of each treatment for hand eczema symptoms is needed.”

References

1. Wittmann M, Smith IL, Brown ST, et al. Alitretinoin versus phototherapy as the first-line treatment in adults with severe chronic hand eczema: the ALPHA RCT. Health Technol Assess. 2024;28(59):1-123. doi:10.3310/TWQC0141
2. Christoffers WA, Coenraads PJ, Svensson Å, et al. Interventions for hand eczema. Cochrane Database Syst Rev. 2019;4(4):CD004055. Published 2019 Apr 26. doi:10.1002/14651858.CD004055.pub2