Background: Erythropoietic protoporphyria (EPP) patients suffer from painful phototoxicity. Sunlight-avoiding behaviour has not yet been quantified objectively in EPP patients. Objective: To study total white light exposure obtained with an actigraph device, before and during afamelanotide treatment, in EPP patients compared to healthy controls. Effects on circadian rhythm, pain and sleep were also investigated. Methods: Adult EPP patients visiting the Porphyria Center Rotterdam of the Erasmus MC were included in this single-center longitudinal case-control open-label intervention study. Controls were age and place of residence matched. Participants wore an actigraph (Actiwatch Pro) during two weeks for multiple periods. Afamelanotide was given to EPP patients as part of standard care. Results: Twenty-six EPP patients and 23 matched controls participated. Controls were statistically significantly more exposed to white light than EPP patients off treatment during autumn (95.4%), spring (69.9%), and summer (105.4%; p = 0.01). EPP patients on afamelanotide treatment had 71.6% more light exposure during spring compared to EPP patients off treatment (p < 0.01). Afamelanotide treatment resulted in a reduction of painful moments in the morning (6.5% decrease) and the evening (8.1% decrease; p < 0.05). Bedtime differed between EPP patients off treatment, controls and EPP patients on treatment (23:45 h ± 1:51 versus 23:02 ± 1:41 and 23:14 ± 1:29, respectively; p < 0.0001). Conclusion: Actigraphy is a useful method to objectively measure white light exposure and treatment effects in EPP. In EPP patients afamelanotide treatment is associated with increased white light exposure during spring, and overall less pain. Treatment with afamelanotide is also associated with normalization of circadian rhythm.
Bibliographical noteFunding Information:
Dr. Langendonk participates in trials sponsored by Clinuvel, including reimbursement for data entry for the European Medicines Agency directed registry for long term safety monitoring of afamelanotide treated and untreated EPP patients. Dr. Langendonk is also involved in industry-sponsored trials by Alnylam. Dr. Wilson reports travel fees from Clinuvel during the development and conduct of the trials and for presentations at the EMA and FDA. No other disclosures were reported.