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Life (Basel, Switzerland) May 2024Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are rare disorders of heme biosynthesis characterized by severe cutaneous phototoxicity....
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 ( < 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.
PubMed: 38929673
DOI: 10.3390/life14060689 -
International Journal of Environmental... May 2024The National Institute for Health and Care Excellence (NICE) in England uses quality-adjusted life years (QALYs) to assess the cost-effectiveness of treatments. A QALY...
Fair Funding Decisions: Consistency of the Time Horizons Used in the Calculation of Quality-Adjusted Life Years for Therapies for Very Rare Diseases by the National Institute for Health and Care Excellence in England.
The National Institute for Health and Care Excellence (NICE) in England uses quality-adjusted life years (QALYs) to assess the cost-effectiveness of treatments. A QALY is a measure that combines the size of the clinical benefit of a treatment with the time the patient benefits from it, i.e., the time horizon. We wanted to know how consistently QALY gains are calculated at NICE. Therefore, we have analysed information on the time horizons used for the QALY calculations of the concluded evaluations conducted under the Highly Specialised Technologies programme for treatments of very rare diseases at NICE. For treatments with final guidance published by December 2023 ( = 29), a time horizon of median 97.5 years (range: 35 to 125 years) was used to calculate the QALY gains. For most QALY calculations, the accepted time horizon was longer than either the expected treatment duration or the estimated life expectancy. In contrast, for the only technology with a final negative funding decision, i.e., afamelanotide for treating the lifelong chronic disease erythropoietic protoporphyria, a time horizon that was shorter than the expected treatment duration was used. The fairness and consistency of the evaluation process of treatments for very rare diseases at NICE should be reviewed.
Topics: Rare Diseases; Quality-Adjusted Life Years; Humans; England; Cost-Benefit Analysis; Decision Making; Time Factors
PubMed: 38791830
DOI: 10.3390/ijerph21050616 -
Postepy Dermatologii I Alergologii Apr 2024Afamelanotide is a synthetic alpha melanocyte stimulating hormone presenting a higher activity than natural hormones. Its main properties are related to the enhanced... (Review)
Review
Afamelanotide is a synthetic alpha melanocyte stimulating hormone presenting a higher activity than natural hormones. Its main properties are related to the enhanced production of eumelanin by agonistically binding to the melanocortin-1 receptor. Since 2016 afamelanotide has been especially applied to treat cases of erythropoietic porphyria (EPP), where painful photosensitivity has been observed since early childhood. The positive effect of afamelanotide in EPP administered subcutaneously improved tolerance to artificial white light and increased pain-free time spent in direct sunlight. In this review we summarize the possible use of afamelanotide in dermatology, with special emphasis on EPP and encourage including afamelanotide as a treatment option in patient care.
PubMed: 38784937
DOI: 10.5114/ada.2024.138818 -
Photodiagnosis and Photodynamic Therapy Jun 2024Protoporphyrin IX (PPIX) is the final precursor of heme, forming heme when iron is inserted. Individuals with erythropoietic protoporphyrias (EPP) have accumulation of... (Review)
Review
BACKGROUND
Protoporphyrin IX (PPIX) is the final precursor of heme, forming heme when iron is inserted. Individuals with erythropoietic protoporphyrias (EPP) have accumulation of PPIX, causing photosensitivity and increased liver disease risk. Many also have iron deficiency and anemia. We investigated outcomes of oral iron supplements in individuals with EPP.
METHODS
A systematic review identified literature on oral iron supplements in EPP patients. Subsequently, we administered iron supplements to EPP patients with iron deficiency. The primary outcome was impact on PPIX level. Secondary outcomes were adverse events and relative differences in hemoglobin and iron parameters.
RESULTS
The systematic review found 13 case reports and one uncontrolled clinical trial with uncertain results. From our department 10 patients with EPP and iron deficiency took daily dosages of 330 mg of ferrous fumarate for two months. Five of our patients had anemia at baseline. After 2 months of supplementation seven patients had increased PPIX level compared to baseline, two had decrease, one remained unchanged. The administration of iron led to a rise in ferritin, and in four of the anemic patients also to an improvement in blood hemoglobin. A small transiently elevation in plasma alanine transaminase concentration was observed during supplementation.
CONCLUSIONS
Overall, iron supplementation in EPP patients replenished iron stores and elevated erythrocyte PPIX and plasma alanine transaminase. For anemic patients, there was some degree of normalization of the hemoglobin level. If iron therapy is needed for EPP patients, monitoring of photosensitivity, PPIX, hemoglobin, and plasma liver enzymes is advisable.
Topics: Humans; Protoporphyria, Erythropoietic; Protoporphyrins; Dietary Supplements; Male; Female; Adult; Iron; Anemia, Iron-Deficiency; Middle Aged; Treatment Outcome
PubMed: 38734198
DOI: 10.1016/j.pdpdt.2024.104211 -
Hematology, Transfusion and Cell Therapy Apr 2024
PubMed: 38719715
DOI: 10.1016/j.htct.2024.02.027 -
Clinical Liver Disease 2024
Review
Diagnosis and management of protoporphyria-related liver dysfunction in erythropoietic protoporphyria and x-linked protoporphyria: A patient-friendly summary of the 2023 evidence-based consensus guidelines.
PubMed: 38487349
DOI: 10.1097/CLD.0000000000000133 -
Microbiology Spectrum Apr 2024Equid alphaherpesvirus 8 (EqHV-8) is one of the most economically important viruses that is known to cause severe respiratory disease, abortion, and neurological...
Equid alphaherpesvirus 8 (EqHV-8) is one of the most economically important viruses that is known to cause severe respiratory disease, abortion, and neurological syndromes in equines. However, no effective vaccines or therapeutic agents are available to control EqHV-8 infection. Heme oxygenase-1 (HO-1) is an antioxidant defense enzyme that displays significant cytoprotective effects against different viral infections. However, the literature on the function of HO-1 during EqHV-8 infection is little. We explored the effects of HO-1 on EqHV-8 infection and revealed its potential mechanisms. Our results demonstrated that HO-1 induced by cobalt-protoporphyrin (CoPP) or HO-1 overexpression inhibited EqHV-8 replication in susceptible cells. In contrast, HO-1 inhibitor (zinc protoporphyria) or siRNA targeting HO-1 reversed the anti-EqHV-8 activity. Furthermore, biliverdin, a metabolic product of HO-1, mediated the anti-EqHV-8 effect of HO-1 via both the protein kinase C (PKC)β/extracellular signal-regulated kinase (ERK)1/ERK2 and nitric oxide (NO)-dependent cyclic guanosine monophosphate (cGMP)-protein kinase G (PKG) signaling pathways. In addition, CoPP protected the mice by reducing the EqHV-8 infection in the lungs. Altogether, these results indicated that HO-1 can be developed as a promising therapeutic strategy to control EqHV-8 infection.IMPORTANCEEqHV-8 infections have threatened continuously donkey and horse industry worldwide, which induces huge economic losses every year. However, no effective vaccination strategies or drug against EqHV-8 infection until now. Our present study found that one host protien HO-1 restrict EqHV-8 replication and . Furthermore, we demonstrate that HO-1 and its metabolite biliverdin suppress EqHV-8 relication via the PKCβ/ERK1/ERK2 and NO/cGMP/PKG pathways. Hence, we believe that HO-1 can be developed as a promising therapeutic strategy to control EqHV-8 infection.
Topics: Horses; Animals; Mice; Heme Oxygenase-1; Cyclic GMP-Dependent Protein Kinases; Biliverdine; Signal Transduction; Virus Replication
PubMed: 38441979
DOI: 10.1128/spectrum.03220-23 -
Zhong Nan Da Xue Xue Bao. Yi Xue Ban =... Nov 2023Erythropoietic protoporphyria (EPP) is an inherited metabolic disease caused by the deficiency in ferrochelatase (FECH) encoded by the gene, and it is inherited in an...
Erythropoietic protoporphyria (EPP) is an inherited metabolic disease caused by the deficiency in ferrochelatase (FECH) encoded by the gene, and it is inherited in an autosomal recessive manner. EPP usually produces acute pain photosensitivity after exposure to sunlight in infancy or early childhood, and liver failure is the most serious associated complication. This article reported an adult female case of EPP complicated with thyrotoxicosis and liver dysfunction which is a rare condition. The patient's liver function improved after liver protection treatment, her thyroid function returned to normal, and her EPP symptoms improved significantly. Moreover, the c.286C>T gene mutation may be the pathogenic locus of EPP. For patients with abnormal liver function, the possibility of EPP should be considered after the common causes are excluded, and gene detection should be done to confirm the diagnosis in time. When EPP is associated with thyrotoxicosis and liver dysfunction, priority may be given to hepatoprotective therapy.
Topics: Humans; Child, Preschool; Female; Adult; Protoporphyria, Erythropoietic; Thyrotoxicosis; Liver Failure; Mutation
PubMed: 38432869
DOI: 10.11817/j.issn.1672-7347.2023.230242 -
Patient Related Outcome Measures 2024Erythropoietic protoporphyria (EPP), a rare inherited disorder, presents in early childhood with severe, painful phototoxicity, with significant impacts on...
Development and Content Validation of Novel Patient-Reported Outcome Measures to Assess Disease Severity and Change in Patients with Erythropoietic Protoporphyria: The EPP Impact Questionnaire (EPIQ).
PURPOSE
Erythropoietic protoporphyria (EPP), a rare inherited disorder, presents in early childhood with severe, painful phototoxicity, with significant impacts on health-related quality of life (HRQoL). Previous studies have not captured all concepts important to patients. Therefore, this study sought to develop a novel, comprehensive, and content valid patient-reported outcome (PRO) measure to assess the efficacy of new therapies.
PATIENTS AND METHODS
Qualitative interviews were conducted with EPP participants and clinical experts to obtain views on concepts relevant to patients. Results informed the development of novel PROs, which were debriefed during subsequent combined concept elicitation and cognitive debriefing interviews.
RESULTS
Twenty-three interviews were conducted with 17 adults and 6 adolescents with EPP. Concept elicitation revealed that participants experienced many symptoms with significant variability. The most common were burning, pain, swelling, and tingling. Tingling was the most common prodromal symptom, while burning was the most bothersome, and pain was the worst full reaction symptom. Participants reported being negatively impacted in their ability to do daily activities, and social and emotional functioning. Many reported impacted ability to work and be productive at their job. Participants reviewed and completed the newly developed PRO measures assessing full reactions and ability to do activities, as well as items to assess severity and change in severity of prodromal symptoms, full reactions, and EPP overall. All measures were found to be comprehensive, clear, and relevant.
CONCLUSION
PRO measures are needed to assess important aspects of HRQoL and evaluate therapeutic response. These PRO measures are unique in assessing overall severity and change in EPP.
PubMed: 38375415
DOI: 10.2147/PROM.S438892