Acute impact of afamelanotide on UVR erythemal and melanogenic responses in healthy humans in vivo: an exploratory study

Afamelanotide, an analogue of α-melanocyte stimulating hormone, activates the melanocortin-1 receptor and has a range of protective properties as demonstrated largely in vitro. While afamelanotide is approved to treat a visible light-induced inflammatory dermatosis, erythropoetic protoporphyria, its acute effects in vivo are poorly characterised. We explored short-term effects of afamelanotide on the acute inflammatory response of UVR-induced erythema and on the melanogenic response, in healthy humans. Participants ( n = 9, 5 M:4 F, 27-43y, phototypes II-III) had melanin density and skin lightness measured at six skin sites using spectrophotometry. A broadband UVB dose-series (7–80 mJ/cm 2 erythemally-weighted UVR, Philips TL12) was applied to buttock skin. After 24 h, minimal erythema dose (MED) was assessed, spectrophotometric measurements were taken of erythema at each dose site and two unexposed sites, and an unexposed site was biopsied. Afamelanotide was administered (16 mg subcutaneous implant) and after six days the same UVR dose-series applied to contralateral buttock skin, and measurements and biopsy repeated. Melanin was stained in biopsy sections (modified Warthin-Starry method) and quantified by image analysis. The UVR-erythema dose response (area-under-curve) decreased post-afamelanotide (mean 3.5 pre, 2.7 post, P = 0.018) with an apparent increase in MED (median 21 mJ/cm 2 pre, 29.9 post, not sign.). Melanin density (reflectance at 420 and 400 nm) increased (mean overall increase 2.4% to 2.9%, P = 0.001), while melanin staining was unaltered. The demonstrated protection against acute UVR-induced erythema shortly after afamelanotide application supports that anti-inflammatory effects observed in vitro may operate in vivo, warranting further investigation in acute UVR-induced inflammatory conditions.