RESUMEN
BACKGROUND: Erythropoietic protoporphyria (EPP) patients experience lifelong painful photosensitivity resulting in a lack of sunlight exposure. Previous studies have shown that 47-63% of EPP patients suffer from vitamin D deficiency and a high prevalence of osteoporosis. As of 2016 an effective treatment for EPP is available: the alpha-MSH analogue afamelanotide. So far studies on vitamin D levels in EPP have only investigated patients who were not treated with afamelanotide. OBJECTIVES: To investigate the effects of afamelanotide treatment on vitamin D levels in EPP. METHODS: A multi-centre observational cohort study, in adult patients with EPP from the Erasmus Medical Centre, the Netherlands and the University Hospital Düsseldorf, Germany. Routinely-collected vitamin D levels between 2005 and 2021 were used for analysis. Patient exposure to cholecalciferol or afamelanotide was categorized into four treatment groups; untreated, cholecalciferol, afamelanotide, and combined treatment. A linear mixed model for longitudinal data was applied to measure the effect of the treatment groups, compared to the untreated, on vitamin D levels. RESULTS: A total of 230 patients and 1774 vitamin D measurements were included. Prevalence of vitamin D deficiency remained high despite afamelanotide treatment: <50 nmol/l in 71.8% of patients, and severe deficiency <30 nmol/l in 48.1%. Afamelanotide treatment alone did not lead to a significant average increase in vitamin D levels (ß:0.5, 95% Confidence Interval [CI]: -3.2 - 4.2). In contrast, cholecalciferol and combined therapy with afamelanotide, led to a significant increase in vitamin D levels (ß:11.6, CI: 7.2-15.9 and ß:15.2, CI: 12.3-18.1). CONCLUSION: Cholecalciferol remains essential for treatment of vitamin D deficiency in EPP, irrespective of new treatment options like afamelanotide. Afamelanotide treatment did not affect vitamin D levels. We suggest that future guidelines include continuous monitoring of vitamin D and prescription of cholecalciferol in all patients with EPP, including those treated with afamelanotide.
