DISTINGUISHING FAMILIAL CHYLOMICRONEMIA: DIAGNOSTIC PITFALLS AND CLINICAL IMPLICATIONS
Author(s)
Dinesh K. Kalra, MD1, Christie M. Ballantyne, MD2, Peter P. Toth, MD, PhD3, Daniel Gaudet, MD, PhD4, Ann Mertens, MD5, Handrean Soran, MSc, MD6, Nathan Kleinman, PhD7, Nathalie Laura Kertesz, PhD8, Jennifer Hellawell, MD8, Nicholas J. Leeper, MD9, Gerald F. Watts, MD, PhD10.
1University of Louisville, Louisville, KY, USA, 2Baylor College of Medicine, Houston, TX, USA, 3Johns Hopkins University School of Medicine, Baltimore, MD, USA, 4Université de Montréal, Montréal, QC, Canada, 5University Hospitals Leuven, Leuven, Belgium, 6Manchester University NHS Foundation Trust, Manchester, United Kingdom, 7Kleinman Analytic Solutions, LLC, Paso Robles, CA, USA, 8Arrowhead Pharmaceuticals, Pasadena, CA, USA, 9Stanford University, Palo Alto, CA, USA, 10University of Western Australia, Perth, Australia.
1University of Louisville, Louisville, KY, USA, 2Baylor College of Medicine, Houston, TX, USA, 3Johns Hopkins University School of Medicine, Baltimore, MD, USA, 4Université de Montréal, Montréal, QC, Canada, 5University Hospitals Leuven, Leuven, Belgium, 6Manchester University NHS Foundation Trust, Manchester, United Kingdom, 7Kleinman Analytic Solutions, LLC, Paso Robles, CA, USA, 8Arrowhead Pharmaceuticals, Pasadena, CA, USA, 9Stanford University, Palo Alto, CA, USA, 10University of Western Australia, Perth, Australia.
OBJECTIVES: Clinical scoring systems, including the North American Familial Chylomicronemia Syndrome (NAFCS) and Moulin scores, were developed to identify patients for genetic testing for FCS, a rare disorder of chylomicron metabolism. This study described the distribution of pre‑treatment NAFCS and Moulin scores in PALISADE and their association with clinical FCS and acute pancreatitis (AP).
METHODS: This post‑hoc analysis included PALISADE patients (N=75), a randomized trial of plozasiran in severe hypertriglyceridemia consistent with FCS who had fasting triglycerides (TG) ≥880 mg/dL, multiple TG ≥1000 mg/dL despite standard-of-care, and ≥1 of: prior genetic FCS diagnosis, prior AP, recurrent hospitalizations for severe abdominal pain without secondary causes, childhood pancreatitis, or family history of hypertriglyceridemia‑induced AP. The cohort included genetically confirmed (n=44) and clinically diagnosed (n=31) FCS. Scores were calculated using pre-treatment data and categorized by established thresholds. Adjudicated AP events were summarized descriptively.
RESULTS: By NAFCS, 33% of patients were classified as “definite FCS” (≥60 points), 28% “likely FCS” (45-59 points), while 39% were uncertain/unlikely FCS (≤44 points). Seven adjudicated AP events occurred across all NAFCS categories, including among patients classified as “uncertain” (1/7) or “unlikely FCS” (2/7). By Moulin score, 64% of patients were categorized as “FCS very likely” (≥10 points), yet 4/7 AP events were observed among patients classified as “unlikely” or “very unlikely”. By NAFCS and Moulin scoring, respectively, 43% and 57% of patients who experienced AP did not meet thresholds for FCS determination.
CONCLUSIONS: NAFCS and Moulin scores showed heterogeneity in classifying patients who experienced AP, with clinically relevant events occurring below traditional FCS thresholds, suggesting score‑based classification alone may be insufficient to identify patients at risk of AP or candidacy for APOC3-targeted therapy. PALISADE eligibility criteria, including TG ≥880 mg/dL and history or family history of abdominal pain or AP events, may better capture clinically relevant AP risk.
METHODS: This post‑hoc analysis included PALISADE patients (N=75), a randomized trial of plozasiran in severe hypertriglyceridemia consistent with FCS who had fasting triglycerides (TG) ≥880 mg/dL, multiple TG ≥1000 mg/dL despite standard-of-care, and ≥1 of: prior genetic FCS diagnosis, prior AP, recurrent hospitalizations for severe abdominal pain without secondary causes, childhood pancreatitis, or family history of hypertriglyceridemia‑induced AP. The cohort included genetically confirmed (n=44) and clinically diagnosed (n=31) FCS. Scores were calculated using pre-treatment data and categorized by established thresholds. Adjudicated AP events were summarized descriptively.
RESULTS: By NAFCS, 33% of patients were classified as “definite FCS” (≥60 points), 28% “likely FCS” (45-59 points), while 39% were uncertain/unlikely FCS (≤44 points). Seven adjudicated AP events occurred across all NAFCS categories, including among patients classified as “uncertain” (1/7) or “unlikely FCS” (2/7). By Moulin score, 64% of patients were categorized as “FCS very likely” (≥10 points), yet 4/7 AP events were observed among patients classified as “unlikely” or “very unlikely”. By NAFCS and Moulin scoring, respectively, 43% and 57% of patients who experienced AP did not meet thresholds for FCS determination.
CONCLUSIONS: NAFCS and Moulin scores showed heterogeneity in classifying patients who experienced AP, with clinically relevant events occurring below traditional FCS thresholds, suggesting score‑based classification alone may be insufficient to identify patients at risk of AP or candidacy for APOC3-targeted therapy. PALISADE eligibility criteria, including TG ≥880 mg/dL and history or family history of abdominal pain or AP events, may better capture clinically relevant AP risk.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
SA1
Topic
Epidemiology & Public Health, Patient-Centered Research, Study Approaches
Disease
Cardiovascular Disorders (including MI, Stroke, Circulatory), No Additional Disease & Conditions/Specialized Treatment Areas