PhD defence D. (Debby) Wensink

Summary:

Erythropoietic protoporphyria (EPP) is a rare inherited disorder of heme biosynthesis, causing painful photosensitivity. This photosensitivity starts at an early age and is present throughout life. At a young age, the patients learn to avoid light exposure, changing their behaviour, including the self-learned restrictions that result in a low quality of life. Until recently, there was no effective therapy for EPP, management consisted of strict avoidance of sunlight and wearing protective clothing. To date, afamelanotide is the only treatment option for EPP. It is challenging to demonstrate a clinically meaningful and statistically significant response to treatment in rare disease studies due to the lack of suitable endpoints, either patient reported outcome (PRO) or disease markers.  

In conclusion, it is demonstrated with real-world data that afamelanotide is safe and more effective during clinical practice to prevent phototoxic symptoms in patients with EPP. Afamelanotide increases the duration of time spent outside and white light exposure, improved quality of life, and results in less severe phototoxic reactions. EPP negatively impacts employment rate and social aspects of wellbeing and is associated with a high prevalence of type D personality. Actigraphy to measure white light exposure and time-to-prodrome are suitable clinical endpoints to investigate treatment effects in EPP patients. For patients with EPP, severe liver disease remains a rare incident. By using elastography, we cannot predict who is at risk to develop severe liver disease, but the observed ‘normal’ prevalence of hepatic steatosis and fibrosis is reassuring for the patients.