Systematic Literature Review SLR Characterizing Humanistic Disease Burden and Unmet Needs in Erythropoietic Protoporphyria (EPP) and X-linked Protoporphyria (XLP)
Author(s)
Bhagyashree Oak, PhD1, Conor Maher, MBiochem1, Abigail Silber, MPH1, Melanie Chin, PhD2, Maria Hall, MA3, Emily Herod, BS2, Adaeze Q. Amaefule, PharmD, MS2, Chelsea Norregaard, MPH, PhD2.
1Trinity Life Sciences, Waltham, MA, USA, 2Disc Medicine, Watertown, MA, USA, 3Maria Hall Consulting Ltd., Slough, United Kingdom.
1Trinity Life Sciences, Waltham, MA, USA, 2Disc Medicine, Watertown, MA, USA, 3Maria Hall Consulting Ltd., Slough, United Kingdom.
OBJECTIVES: Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are rare, genetic disorders affecting heme biosynthesis. EPP/XLP cause severe photosensitivity resulting in patients adopting significant behavioral modifications to avoid phototoxic reactions. This systematic literature review (SLR) aimed to characterize the clinical, economic, and humanistic (e.g., psychosocial, quality of life [QoL]) burden of patients with EPP/XLP, including an evaluation of QoL using patient reported outcome measures (PROMs).
METHODS: An SLR was conducted of peer-reviewed manuscripts published from January 2014-January 2025, and conference abstracts, published from January 2019-January 2025, in PubMed and Embase. The research was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and studies were assessed using Cochrane Risk of Bias tools. Two independent reviewers conducted title-abstract/full-text screenings with conflicts adjudicated by a third reviewer.
RESULTS: Of the 520 studies identified, 46 were included. Eighteen studies reported on EPP/XLP symptoms which included pain, burning, and tingling, and ten studies reported on comorbidities, including hepatobiliary manifestations. Twelve studies evaluated QoL using PROMs, and eleven studies assessed humanistic burden via other qualitative or incommensurate metrics. Several PROMs were used, including EPP-QoL (n=8), PROMIS-57 (n=2), PGI-C (n=2), EPIQ (n=1), and HADS (n=1). Two studies demonstrated that a substantial proportion of patients with EPP/XLP were diagnosed with depression/anxiety with 20% of patients scoring abnormal/borderline-abnormal for anxiety via HADS. Ten studies emphasize the burden of behavioral modifications in patients with EPP/XLP, including sunlight avoidance, missed work/school, protective clothing, altered vacations, and career adjustments.
CONCLUSIONS: Patients with EPP/XLP experience a substantial burden from symptoms, comorbidities, and lifestyle modifications. This SLR also reveals a lack of consensus on appropriate PROMs to evaluate QoL in EPP/XLP. With one approved therapy available for adult patients with EPP and none for XLP or pediatric patients, a significant unmet need remains for effective treatments that address the humanistic burden of EPP/XLP.
METHODS: An SLR was conducted of peer-reviewed manuscripts published from January 2014-January 2025, and conference abstracts, published from January 2019-January 2025, in PubMed and Embase. The research was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and studies were assessed using Cochrane Risk of Bias tools. Two independent reviewers conducted title-abstract/full-text screenings with conflicts adjudicated by a third reviewer.
RESULTS: Of the 520 studies identified, 46 were included. Eighteen studies reported on EPP/XLP symptoms which included pain, burning, and tingling, and ten studies reported on comorbidities, including hepatobiliary manifestations. Twelve studies evaluated QoL using PROMs, and eleven studies assessed humanistic burden via other qualitative or incommensurate metrics. Several PROMs were used, including EPP-QoL (n=8), PROMIS-57 (n=2), PGI-C (n=2), EPIQ (n=1), and HADS (n=1). Two studies demonstrated that a substantial proportion of patients with EPP/XLP were diagnosed with depression/anxiety with 20% of patients scoring abnormal/borderline-abnormal for anxiety via HADS. Ten studies emphasize the burden of behavioral modifications in patients with EPP/XLP, including sunlight avoidance, missed work/school, protective clothing, altered vacations, and career adjustments.
CONCLUSIONS: Patients with EPP/XLP experience a substantial burden from symptoms, comorbidities, and lifestyle modifications. This SLR also reveals a lack of consensus on appropriate PROMs to evaluate QoL in EPP/XLP. With one approved therapy available for adult patients with EPP and none for XLP or pediatric patients, a significant unmet need remains for effective treatments that address the humanistic burden of EPP/XLP.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
SA87
Topic
Patient-Centered Research, Study Approaches
Topic Subcategory
Literature Review & Synthesis
Disease
Rare & Orphan Diseases, Systemic Disorders/Conditions (Anesthesia, Auto-Immune Disorders (n.e.c.), Hematological Disorders (non-oncologic), Pain)