Association of Afamelanotide With Improved Outcomes in Patients With Erythropoietic Protoporphyria in Clinical Practice

Abstract

rythropoietic protoporphyria (EPP) (OMIM 177000) is a rare inherited disorder of heme biosynthesis, causing painful photosensitivity. 1 Erythropoietic protoporphyria is caused by FECH or ALAS2 gene mutations, leading to protoporphyrin IX accumulation in erythroid cells. 2,3 It severely affects patients' quality of life (QoL) 4 by causing severe pain after light exposure, which lasts several days and is unresponsive to analgesics. 2,5 This results in sunlightavoiding behavior, limiting daily and social activities. 4 Until recently, there was no effective therapy for EPP 6,7 ; management consisted of strict avoidance of sunlight and wearing protective clothing. In 2016, afamelanotide became available after the European Medicines Agency recommended approval in the European Union with an obligatory postauthorization safety and efficacy study. Afamelanotide is a potent α-melanocyte-stimulating hormone analogue, which increases eumelanin and stimulates anti-inflammatory and antioxidative pathways. 8 Placebo-controlled trials demonstrated statistically significant effects but a relatively small reduction in EPP symptoms. 9,10 We report on the association of afamelanotide treatment with outcomes in EPP in regular practice during longer-term follow-up. MethodsIn this single-center, prospective postauthorization safety and efficacy cohort study of afamelanotide, all adult patients with a confirmed diagnosis of EPP attending the outpatient clinic of the Erasmus University Medical Center in Rotterdam, the Netherlands, were eligible for inclusion (eFigure in the Supplement). Afamelanotide was offered as a controlled-release 16-mg IMPORTANCE The effectiveness of afamelanotide treatment in patients with erythropoietic protoporphyria (EPP) in clinical practice who experience pain after light exposure that substantially impairs quality of life is unknown.OBJECTIVE To evaluate the association of afamelanotide treatment with outcomes in patients with EPP in regular practice during longer-term follow-up. DESIGN, SETTING, AND PARTICIPANTSThis single-center, prospective postauthorization safety and efficacy cohort study was directed and approved by the European Medicines Agency. Data were collected from patients with EPP treated with afamelanotide at Erasmus MC between June 2016 and September 2018. Analysis began October 2018.MAIN OUTCOMES AND MEASURES Time spent outside during treatment, number of phototoxic reactions, disease-specific quality of life, usage of protective clothing, and adverse events.RESULTS A total of 117 patients with EPP (59 women [50.4%]; mean [SD] age, 43.0 [15.5] years) were treated with afamelanotide. Nearly all patients continued treatment (115 [98%]) with a median (interquartile range) follow-up of 2.0 (1.3-2.1) years. Compared with baseline, mean time spent outside during treatment increased significantly by an added 6.1 hours per week (95% CI, 3.62-8.67; P < .001). Mean quality of life score improved significantly by 14.01% (95% CI, 4.53%-23.50%; P < .001). Phototoxic reactions were less painful (β, −0.85;...

Increased phototoxic burn tolerance time and quality of life in patients with erythropoietic protoporphyria treated with afamelanotide – a three years observational study

“…The limitations of our study lie in the retrospective and observational nature of the study design and the limited number of participants. However, such a design is considered suitable in ultra-rare conditions such as EPP and is often used in post-admission surveillance for noxious side effects [ 28 , 34 ].…”

Afamelanotide for prevention of phototoxicity in erythropoietic protoporphyria

“…Most frequently reported were nausea, fatigue, flushing, and nausea with headache. No related serious adverse events occurred during the study [72]. Skin hyperpigmentation is the most prominent visible effect of afamelanotide; some patients reported increased skin pigmentation and darkening of preexisting nevi and ephelides.…”

“…Patients were also treated with 16 mg afamelanotide implants with a minimum interval of 60 days, max four implants per year. This observational study, based on the EMA requested PASS protocol, demonstrated clinically significant, and sustained, positive effects on quality of life (an improvement of 14% on the EPP QoL), increased reported duration of light exposure with an added 6.1 hours per week and less painful phototoxic reactions [72]. Recently, a study was published introducing the new endpoint phototoxic burn protection factor (PBTT) for assessing treatment effect in EPP.…”

Alternative Pathway Involvement in Protoporphyria Patients Related to Sun Exposure

“…To improve the quality of life of the patients for several diseases, the management of symptoms and pain is of utmost importance ( 35 , 36 ). Likewise, for PP, a constant challenge prevails in daily life to avoid the pain that leads to reduced quality of life ( 37 ). Moreover, analgesic drugs fail to relieve the pain in PP ( 31 ).…”