Erythropoietic protoporphyria: time to prodrome, the warning signal to exit sun exposure without pain—a patient-reported outcome efficacy measure

D. Wensink, J. G. Langendonk, J. R. Overbey, M. Balwani, E. J.E. Van Broekhoven, M. A.E.M. Wagenmakers, J. H.P. Wilson, K. Wheeden, H. Naik, R. J. Desnick*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

8 Citations (Scopus)


Purpose: Patients with erythropoietic protoporphyria (EPP), a severe painful photodermatosis, experience prodromal sensations when exposed to sunlight, which are the “warning signals” to exit the sun, as prolonged exposure causes an excruciatingly painful phototoxic attack. The unique prodromal cutaneous sensations are reversible and differ from the severe burning pain attack lasting 2–7 days. Previously, afamelanotide treatment was studied using time to pain or time outside as primary outcome measures. Since patients have an ingrained fear of sunlight, these measures did not capture the full treatment effect. We retrospectively characterized and evaluated time to prodrome (TTP) as a safer, patient-reported outcome (PRO) measure in afamelanotide-treated patients. Methods: Structured interviews recorded TTP before and during afamelanotide treatment in retrospective US and Dutch cohort studies. Results: Thirty-one US and 58 Dutch EPP patients participated. Before afamelanotide treatment, 54.8% US and 39.7% Dutch patients reported TTP onset <10 minutes in direct sunlight. In both studies, patients’ TTP’s were significantly longer during afamelanotide treatment (p < 0.0001). All US patients’ TTP increased; no TTP was <10 minutes. Among Dutch patients 81% improved; only 10.3% reported TTPs < 10 minutes. Conclusion: EPP patients reported substantial improvements in TTP during afamelanotide treatment. TTP could provide a safer, PRO-based efficacy endpoint for assessing future EPP treatments.

Original languageEnglish
Pages (from-to)1616-1623
Number of pages8
JournalGenetics in Medicine
Issue number9
Early online date3 May 2021
Publication statusPublished - Sept 2021

Bibliographical note

Funding Information:
J.G.L. report financial support from Clinuvel to cover expenses incurred for data entry for the European Medicines Agency–directed afamelanotide registry. J.H.P.W. reports grants and travel fees from Clinuvel during the conduct of the study. R.J.D. is a consultant for Mitsubishi Tanabe Pharma America. The other authors declare no competing interests.

Funding Information:
This research was supported by the Department of Genetics and Genomic Sciences, Icahn School of Medicine, New York City; the Department of Internal Medicine, Erasmus MC Rotterdam, and the American Porphyria Foundation. This research was presented by Wensink et al. at a plenary session on 11 September 2019 during the International Congress of Porphyrins and Porphyrias (held 8–11 September 2019).

Publisher Copyright:
© 2021, The Author(s), under exclusive licence to the American College of Medical Genetics and Genomics.


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