Afamelanotide Is Associated with Dose-Dependent Protective Effect from Liver Damage Related to Erythropoietic Protoporphyria
Abstract
:1. Introduction
2. Patients, Material, and Methods
2.1. Patients, Treatment Schedules, and Safety Measurements
2.2. Data Sources and Statistical Analysis
2.3. Assessment of Dose-Dependent Effects of Afamelanotide
2.4. Further Statistical Analyses
3. Results
3.1. General Correlations between LFTs and PPIX
3.2. Distributions of the Indexidr and Indexcde
3.3. Global Radiation as an Independent Effector
3.4. Immediate Dose-Response and Cumulative Dose Effect of Afamelanotide on PPIX Concentrations and LFTs (Table 1)
3.5. Influence of Global Radiation on PPIX Concentrations and LFTs as Assayed by Multilinear Regression Analysis (Table 1)
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
ALAS2 | aminolevulinic acid synthase 2 |
ALAT | alanine transaminase |
ASAT | aspartate transaminase |
CDE | cumulative dose effect |
EMA | European medicine agency |
EPP | erythropoietic protoporphyria |
FDA | U.S. Food and Drug Administration |
GGT | gamma-glutamyltransferase |
IDR | immediate dose response |
IκB | inhibitor of nuclear factor-kappa-B |
LFT | liver function tests |
MCR | melanocortin receptor |
MSH | melanocyte-stimulating hormone |
NF-κB | nuclear factor-kappa-B |
PPIX | protoporphyrin |
TGA | Therapeutic Goods Administration |
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Dependent Variable | Model p-Value | Independent Variables | |||
---|---|---|---|---|---|
Patient ID p-Value | Second Independent Variable | ||||
Name | p Value | Effect | |||
PPIX | <0.0001 | <0.0001 | indexIDR | <0.0001 | 0.008376 |
PPIX | <0.0001 | <0.0001 | indexCDE365 | <0.0001 | −0.8043 |
PPIX | <0.0001 | <0.0001 | Relative global radiation | 0.0113 | −1.059 |
ALAT | 0.0008 | 0.0008 | indexIDR | 0.1625 | 0.009162 |
ALAT | 0.0003 | 0.0005 | indexCDE365 | 0.012 | −2.509 |
ALAT | 0.001 | 0.0008 | Relative global radiation | 0.263 | −3.6 |
ASAT | <0.0001 | <0.0001 | indexIDR | 0.1074 | 0.004727 |
ASAT | <0.0001 | <0.0001 | indexCDE365 | 0.1606 | −0.5345 |
ASAT | <0.0001 | <0.0001 | Relative global radiation | 0.4277 | −1.086 |
Bilirubin | <0.0001 | <0.0001 | indexIDR | 0.9527 | −5.90 × 10−5 |
Bilirubin | <0.0001 | <0.0001 | indexCDE365 | 0.0299 | −0.304 |
Bilirubin | <0.0001 | <0.0001 | Relative global radiation | 0.5845 | 0.2239 |
GGT | <0.0001 | <0.0001 | indexIDR | 0.2044 | 0.01082 |
GGT | <0.0001 | <0.0001 | indexCDE365 | 0.1846 | −1.668 |
GGT | <0.0001 | <0.0001 | Relative global radiation | 0.4821 | −2.475 |
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Minder, A.-E.; Schneider-Yin, X.; Zulewski, H.; Minder, C.E.; Minder, E.I. Afamelanotide Is Associated with Dose-Dependent Protective Effect from Liver Damage Related to Erythropoietic Protoporphyria. Life 2023, 13, 1066. https://doi.org/10.3390/life13041066
Minder A-E, Schneider-Yin X, Zulewski H, Minder CE, Minder EI. Afamelanotide Is Associated with Dose-Dependent Protective Effect from Liver Damage Related to Erythropoietic Protoporphyria. Life. 2023; 13(4):1066. https://doi.org/10.3390/life13041066
Chicago/Turabian StyleMinder, Anna-Elisabeth, Xiaoye Schneider-Yin, Henryk Zulewski, Christoph E. Minder, and Elisabeth I. Minder. 2023. "Afamelanotide Is Associated with Dose-Dependent Protective Effect from Liver Damage Related to Erythropoietic Protoporphyria" Life 13, no. 4: 1066. https://doi.org/10.3390/life13041066