PDF(Pubmed)
Abstract：
BACKGROUND: Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are rare disorders of heme biosynthesis characterized by severe cutaneous phototoxicity. Afamelanotide, an α-melanocyte-stimulating hormone analogue, is the only approved treatment for protoporphyria and leads to increased light tolerance and improved quality of life (QoL). However, published experience with afamelanotide in the US is limited.
METHODS: Here, we report on all adults who received at least one dose of afamelanotide at the Massachusetts General Hospital Porphyria Center from 2021 to 2022. Changes in the time to phototoxic symptom onset, QoL, and laboratory parameters were assessed before and during treatment with afamelanotide.
RESULTS: A total of 29 patients with protoporphyria were included, 26 of whom (72.2%) received ≥2 afamelanotide implants. Among the patients who received ≥2 implants, the median time to symptom onset following sunlight exposure was 12.5 min (IQR, 5-20) prior to the initiation of afamelanotide and 120 min (IQR, 60-240) after treatment (p < 0.001). Improvements in QoL during afamelanotide treatment were measured using two QoL tools, with good correlation observed between these two instruments. Finally, we found no improvements in the median levels of metal-free erythrocyte protoporphyrin, plasma protoporphyrin, or liver biochemistries during versus prior to the initiation of afamelanotide treatment.
CONCLUSIONS: This study highlights a dramatic clinical benefit of afamelanotide in relation to light tolerance and QoL in protoporphyria, albeit without improvement in protoporphyrin levels or measures of liver function.
METHODS: Here, we report on all adults who received at least one dose of afamelanotide at the Massachusetts General Hospital Porphyria Center from 2021 to 2022. Changes in the time to phototoxic symptom onset, QoL, and laboratory parameters were assessed before and during treatment with afamelanotide.
RESULTS: A total of 29 patients with protoporphyria were included, 26 of whom (72.2%) received ≥2 afamelanotide implants. Among the patients who received ≥2 implants, the median time to symptom onset following sunlight exposure was 12.5 min (IQR, 5-20) prior to the initiation of afamelanotide and 120 min (IQR, 60-240) after treatment (p < 0.001). Improvements in QoL during afamelanotide treatment were measured using two QoL tools, with good correlation observed between these two instruments. Finally, we found no improvements in the median levels of metal-free erythrocyte protoporphyrin, plasma protoporphyrin, or liver biochemistries during versus prior to the initiation of afamelanotide treatment.
CONCLUSIONS: This study highlights a dramatic clinical benefit of afamelanotide in relation to light tolerance and QoL in protoporphyria, albeit without improvement in protoporphyrin levels or measures of liver function.
摘要：
背景：红细胞生成性原卟啉症（EPP）和X连锁原卟啉症（XLP）是罕见的血红素生物合成障碍，其特征是严重的皮肤光毒性。Afamelanotide,一种α-黑素细胞刺激激素类似物,是唯一批准的治疗原卟啉症的方法，可提高光耐受性和改善生活质量（QoL）。然而,在美国发表的阿非美拉诺肽的经验有限。
方法：这里，我们报告了从2021年到2022年在马萨诸塞州总医院卟啉病中心接受至少一剂阿非美拉诺肽治疗的所有成年人.光毒性症状发作时间的变化，QoL,在使用阿非美拉诺肽治疗之前和期间评估了实验室参数。
结果：共纳入29例原卟啉患者，其中26人（72.2%）接受了≥2次阿夫拉诺肽植入物。在接受≥2次植入物的患者中，阳光照射后症状发作的中位时间为12.5分钟(IQR，5-20)在开始阿非美拉诺肽之前和120分钟(IQR，60-240）治疗后（p<0.001）。使用两种QoL工具测量了afamelanotide治疗期间QoL的改善，在这两种仪器之间观察到良好的相关性。最后,我们发现无金属红细胞原卟啉的中位数水平没有改善，血浆原卟啉，或在开始阿非美拉诺肽治疗之前的肝脏生物化学。
结论：这项研究强调了阿非美拉诺肽与光耐受性和QoL相关的显着临床益处，虽然没有改善原卟啉水平或肝功能的措施。
方法：这里，我们报告了从2021年到2022年在马萨诸塞州总医院卟啉病中心接受至少一剂阿非美拉诺肽治疗的所有成年人.光毒性症状发作时间的变化，QoL,在使用阿非美拉诺肽治疗之前和期间评估了实验室参数。
结果：共纳入29例原卟啉患者，其中26人（72.2%）接受了≥2次阿夫拉诺肽植入物。在接受≥2次植入物的患者中，阳光照射后症状发作的中位时间为12.5分钟(IQR，5-20)在开始阿非美拉诺肽之前和120分钟(IQR，60-240）治疗后（p<0.001）。使用两种QoL工具测量了afamelanotide治疗期间QoL的改善，在这两种仪器之间观察到良好的相关性。最后,我们发现无金属红细胞原卟啉的中位数水平没有改善，血浆原卟啉，或在开始阿非美拉诺肽治疗之前的肝脏生物化学。
结论：这项研究强调了阿非美拉诺肽与光耐受性和QoL相关的显着临床益处，虽然没有改善原卟啉水平或肝功能的措施。
