A New Phototherapy Regimen Coupled with Oral Vitamin D Supplementation, for the Long-Term Control of Atopic Dermatitis: A French Multicenter, Randomized, Crossover, Pragmatic Trial.

INTRODUCTION: The global burden of atopic dermatitis (AD) will continue to rise in the coming two decades, underscoring the need for affordable and globally accessible therapies given restricted access to high-cost medications in many regions. The study aimed to evaluate the efficacy of a novel phototherapy-based regimen as an add-on therapy, together with vitamin D supplementation, on long-term disease control in AD. METHODS: The PRADA trial combined two independent randomizations within the same population: an open-label, crossover comparison of narrowband ultraviolet B (NB-UVB) phototherapy versus observation, and a double-blind, parallel-group comparison of vitamin D versus placebo, both superimposed on standard topical anti-inflammatory treatments (TAT). It was conducted between 2015 and 2023 across 16 French hospital centers. The trial included patients aged ≥ 15 years with moderate-to-severe (IGA > 2) AD and with fewer than 100 lifetime phototherapy sessions. The primary outcome was a hierarchical composite endpoint based on: (1) repeated measures of Patient-Oriented SCORing Atopic Dermatitis (PO-SCORAD) severity score over 1 year; and (2) the cumulative use of TAT from October to March. RESULTS: A total of 53 participants were allocated to the vitamin D (26 received NB-UVB during the first period), and 57 to the placebo (27 received NB-UVB during the first period). A total of 93 participants were available for the main analysis for the primary endpoint. Vitamin D was significantly associated with lower PO-SCORAD scores compared with placebo (mean [95% CI] difference -5.6 [-12.1 to -1.78]), however, this effect size remained below the prespecified minimum clinically important difference (nine points). NB-UVB showed no significant effect on PO-SCORAD scores (mean difference: 1.25 [-3.90 to 1.40]). Adverse event incidence was 0.33 per 100 patient-months, mainly nonserious photosensitivity reactions (n = 38). CONCLUSIONS: In the PRADA trial (underpowered due to a recruitment short fall), NB-UVB phototherapy showed no clinically meaningful benefit on the long-term control of moderate-to-severe AD. The observed benefit of vitamin D supplementation on PO-SCORAD, although statistically significant, did not reach the threshold for clinical relevance. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02537509.