SAT-248 A Case Series of Heterozygous Familial Hypercholesteremia With PCSK9 Inhibitor Failure
Notice bibliographique
Résumé
Abstract Disclosure: A. Varghese: None. R.A. Hegele: None. A. Berberich: None. Background: Monoclonal antibodies (MABs) to proprotein convertase subtilisin/kexin 9 (PCSK9) are commonly used to treat heterozygous familial hypercholesterolemia (HeFH). Both evolocumab and alirocumab have demonstrated efficacy in reducing low-density-lipoprotein cholesterol (LDL-C) in patients with HeFH. While a few reports describing patients with initial non-response to PCSK9 MAbs, with proposed mechanisms including the development of anti-drug antibodies, medication injection technique and LDLR variant classification, we describe here the rare scenario of initial robust response followed by subsequent loss of response to PCSK9 MAbs in two individuals with HeFH.CASE 1: A 60-year-old woman with a history of relapsing polychondritis was evaluated for dyslipidemia with an initial LDL-C of 6.49mmol/L (251mg/dL). She was diagnosed with HeFH via clinical criteria. Despite treatment with rosuvastatin 40mg daily, LDL-C remained high at 5.35mmol/L (207mg/dL). Evolocumab 140mg every 2 weeks was started and her LDL-C improved to 0.97mmol/L (36.4mg/dL). After one year of stable response, her LDL-C increased to 6.00mmol/L (232mg/dL) despite ongoing treatment. Evolocumab was switched to alirocumab which initially reduced her LDL-C to 2.65 mmol/L (102.5 mg/dL), but it later rose again. Ezetimibe 10mg daily was added and patient is awaiting approval for inclisiran.CASE 2: An 18-year-old woman with type 1 diabetes and celiac disease was seen in September 2012 for dyslipidemia. Prior statin and ezetimibe treatments were discontinued due to myalgias. Her initial LDL-C was 7.23mmol/L (279.6mg/dL). Genetic testing revealed a heterozygous pathogenic LDLR variant (p.Gly723Ter). Pravastatin 40 mg was started but discontinued due to myalgias. Evolocumab 140 mg every two weeks was initiated, and her LDL-C improved to 3.26 mmol/L (126.1 mg/dL). However, after a year, her LDL-C rose to 7.72 mmol/L (298.5 mg/dL). Switching to alirocumab reduced her LDL-C to 1.76 mmol/L (68.1 mg/dL), but within three years, it increased again to 7.65 mmol/L (295.8 mg/dL). Ezetimibe 10 mg daily was reintroduced, but the patient continues to experience refractory hyperlipidemia. Discussion: These two cases demonstrate an unusual loss of response to PCSK9 MAbs after initial successful reduction in LDL-C. We have identified only one other report describing this clinical phenomenon in a patient taking alirocumab. The mechanism underlying these observations is unclear but could include the development of neutralizing antibodies. Both patients described here have a history of autoimmunity, which may suggest a common causal link. Further research is needed to understand the underlying mechanisms and the likelihood of this occurring in other patients. These cases also highlight the need for ongoing vigilance in patients with high cholesterol and HeFH to ensure optimal cardiovascular protection. Presentation: Saturday, July 12, 2025
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».