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Afamelanotide for Erythropoietic Protoporphyria
#MMPMID26132941
Langendonk JG
; Balwani M
; Anderson KE
; Bonkovsky HL
; Anstey AV
; Bissell DM
; Bloomer J
; Edwards C
; Neumann NJ
; Parker C
; Phillips JD
; Lim HW
; Hamzavi I
; Deybach JC
; Kauppinen R
; Rhodes LE
; Frank J
; Murphy GM
; Karstens FPJ
; Sijbrands EJG
; de Rooij FWM
; Lebwohl M
; Naik H
; Goding CR
; Wilson JHP
; Desnick RJ
N Engl J Med
2015[Jul]; 373
(1
): 48-59
PMID26132941
show ga
BACKGROUND: Erythropoietic protoporphyria is a severe photodermatosis that is
associated with acute phototoxicity. Patients with this condition have
excruciating pain and a markedly reduced quality of life. We evaluated the safety
and efficacy of an ?-melanocyte-stimulating hormone analogue, afamelanotide, to
decrease pain and improve quality of life. METHODS: We conducted two multicenter,
randomized, double-blind, placebo-controlled trials of subcutaneous implants
containing 16 mg of afamelanotide. Patients in the European Union (74 patients)
and the United States (94 patients) were randomly assigned, in a 1:1 ratio, to
receive a subcutaneous implant containing either afamelanotide or placebo every
60 days (a total of five implants in the European Union study and three in the
U.S study). The type and duration of sun exposure, number and severity of
phototoxic reactions, and adverse events were recorded over the respective
180-day and 270-day study periods. Quality of life was assessed with the use of
validated questionnaires. A subgroup of U.S. patients underwent photoprovocation
testing. The primary efficacy end point was the number of hours of direct
exposure to sunlight without pain. RESULTS: In the U.S. study, the duration of
pain-free time after 6 months was longer in the afamelanotide group (median, 69.4
hours, vs. 40.8 hours in the placebo group; P=0.04). In the European Union study,
the duration of pain-free time after 9 months was also longer in the
afamelanotide group than in the placebo group (median, 6.0 hours vs. 0.8 hours;
P=0.005), and the number of phototoxic reactions was lower in the the
afamelanotide group (77 vs. 146, P=0.04). In both trials, quality of life
improved with afamelanotide therapy. Adverse events were mostly mild; serious
adverse events were not thought to be related to the study drug. CONCLUSIONS:
Afamelanotide had an acceptable side-effect and adverse-event profile and was
associated with an increased duration of sun exposure without pain and improved
quality of life in patients with erythropoietic protoporphyria. (Funded by
Clinuvel Pharmaceuticals and others; ClinicalTrials.gov numbers, NCT01605136 and
NCT00979745.).
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