Novel Use of Therapeutic Plasma Exchange and Evinacumab in a Patient with Homozygous Familial Hypercholesterolemia

Abstract

<h3>Lead Author's Financial Disclosures</h3> Nothing to disclose. <h3>Study Funding</h3> None. <h3>Background/Synopsis</h3> We present a 47-year-old woman with homozygous familial hypercholesterolemia (HoFH), recurrent ASCVD events, and multiple intolerances to therapy (including lipoprotein apheresis) who was treated successfully with a unique combination of therapeutic plasma exchange (TPE) and pharmacotherapy, including evinacumab. Her treatment with TPE required 1) pre-medication to prevent allergic reactions, 2) use of a specific TPE system selected to reduce risk of allergic reactions, and 3) medical flights bi-monthly across California to perform TPE at our institution. Following initiation of evinacumab, the patient achieved persistent low levels of LDL-C and subsequently discontinued TPE. <h3>Objective/Purpose</h3> To describe the novel use of TPE and evinacumab in HoFH when treatment options are limited. <h3>Methods</h3> Patient consent was obtained. A review of the electronic health records for the patient was completed. <h3>Results</h3> A 47-year-old woman was referred to our Advanced Lipid Disorders Treatment Center for management of HoFH. Genetic testing revealed a heterozygous pathogenic variant in LDLR; however, phenotypically her presentation was consistent with HoFH (initial LDL-C 356 mg/dL, recurrent myocardial infarction, and repeated revascularization starting at age 39 years, and extensive family history of dyslipidemia and early myocardial infarction). The following treatments were attempted: statin therapy (caused intense, intolerable myalgia), lomitapide (caused intractable vomiting and diarrhea), and lipoprotein apheresis (anaphylactoid-like reaction ultimately thought due to ethylene oxide sterilant in the apheresis column and tubing). She tolerated ezetimibe, bempedoic acid, and PCSK9 inhibitor monoclonal antibodies; however, atherogeniclipid-loweringg was insufficient with this regimen (mean+/-SD LDL-C over 1 year: 234.33+/-13.47 mg/dL). Therefore, TPE was initiated with a system that utilizes tubing sterilized via gamma irradiation, however patient still received empiric pretreatment with antihistamines and steroids. This was successful but required the patient to travel by medical flight to receive TPE every 2 weeks. After initiating evinacumab, the patient achieved persistently low LDL-C levels and TPE was successfully discontinued (Figure). <h3>Conclusions</h3> HoFH is a rare genetic disorder that portends high morbidity and early mortality. Patients with HoFH who are intolerant of treatments due to side-effects and allergies represent a unique challenge to the clinical lipid specialist. We present a patient with limited therapeutic options who was responsive to bi-monthly TPE. Similar to what has been observed in clinical trials with lipoprotein apheresis, our patient with HoFH was able to discontinue TPE following initiation of evinacumab. Our patient is tolerating her current therapy, no longer makes bi-monthly medical flights to our center for TPE, and has maintained low levels of atherogenic lipids.