D Wensink1, J G Langendonk1, J R Overbey2, M Balwani3, E J E Van Broekhoven1, M A E M Wagenmakers1, J H P Wilson3, K Wheeden4, H Naik3, R J Desnick5. 1. Porphyria Center Rotterdam, Center for Lysosomal and Metabolic Disease, Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Erasmus, MC, The Netherlands. 2. Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 3. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 4. American Porphyria Foundation, Bethesda, MD, USA. 5. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Robert.desnick@mssm.edu.
Abstract
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.
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.
Authors: Jasmin Barman-Aksözen; Paulina C Wiek; Vijay B Bansode; Frank Koentgen; Judith Trüb; Pawel Pelczar; Paolo Cinelli; Xiaoye Schneider-Yin; Daniel Schümperli; Elisabeth I Minder Journal: Dis Model Mech Date: 2017-01-12 Impact factor: 5.758