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

Question  What is the association of afamelanotide treatment with outcomes for patients with erythropoietic protoporphyria in clinical practice?

Findings  This postauthorization safety and efficacy cohort study of 117 patients with erythropoietic protoporphyria showed an association with increased time spent outside (6.1 hours/week) and quality of life score (14%) during treatment with afamelanotide; phototoxic reactions were less painful. Minor and self-limiting adverse events were reported, such as nausea, fatigue, and headache.

Meaning  In routine clinical practice, afamelanotide treatment may be more effective in preventing phototoxic effects than previously estimated during placebo-controlled trials.

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 Participants  This 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; 95% CI, −1.43 to −0.26; P < .001), but there was no significant difference in number or duration of reactions. Minor self-limiting adverse events occurred, such as nausea, fatigue, and headache.

Conclusions and Relevance  This cohort study found that afamelanotide treatment was associated with improved clinical outcomes and a good safety profile for patients with EPP. The treatment has clinically significant, sustained positive associations with quality of life, is associated with increased duration of sun exposure, and is associated with less severe phototoxic reactions.