scholarly journals Long-term efficacy of lipoprotein apheresis and lomitapide in the treatment of homozygous familial hypercholesterolemia (HoFH): a cross-national retrospective survey

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Laura D’Erasmo ◽  
Antonio Gallo ◽  
Angelo Baldassare Cefalù ◽  
Alessia Di Costanzo ◽  
Samir Saheb ◽  
...  
Keyword(s):  
Familial Hypercholesterolemia ◽  
Treatment Algorithm ◽  
Lipid Lowering ◽  
Homozygous Familial Hypercholesterolemia ◽  
Lipoprotein Apheresis ◽  
Term Efficacy ◽  
Threatening Condition ◽  
Life Threatening

Abstract Background Homozygous familial hypercholesterolemia (HoFH) is a rare life-threatening condition that represents a therapeutic challenge. The vast majority of HoFH patients fail to achieve LDL-C targets when treated with the standard protocol, which associates maximally tolerated dose of lipid-lowering medications with lipoprotein apheresis (LA). Lomitapide is an emerging therapy in HoFH, but its place in the treatment algorithm is disputed because a comparison of its long-term efficacy versus LA in reducing LDL-C burden is not available. We assessed changes in long-term LDL-C burden and goals achievement in two independent HoFH patients’ cohorts, one treated with lomitapide in Italy (n = 30) and the other with LA in France (n = 29). Results The two cohorts differed significantly for genotype (p = 0.004), baseline lipid profile (p < 0.001), age of treatment initiation (p < 0.001), occurrence of cardiovascular disease (p = 0.003) as well as follow-up duration (p < 0.001). The adjunct of lomitapide to conventional lipid-lowering therapies determined an additional 58.0% reduction of last visit LDL-C levels, compared to 37.1% when LA was added (padj = 0.004). Yearly on-treatment LDL-C < 70 mg/dl and < 55 mg/dl goals were only achieved in 45.5% and 13.5% of HoFH patients treated with lomitapide. The long-term exposure to LDL-C burden was found to be higher in LA than in Lomitapide cohort (13,236.1 ± 5492.1 vs. 11,656.6 ± 4730.9 mg/dL-year respectively, padj = 0.002). A trend towards fewer total cardiovascular events was observed in the Lomitapide than in the LA cohort. Conclusions In comparison with LA, lomitapide appears to provide a better control of LDL-C in HoFH. Further studies are needed to confirm this data and establish whether this translates into a reduction of cardiovascular risk.

scholarly journals Rare Treatments for Rare Dyslipidemias: New Perspectives in the Treatment of Homozygous Familial Hypercholesterolemia (HoFH) and Familial Chylomicronemia Syndrome (FCS)

2021 ◽  
Vol 23 (11) ◽  
Author(s):  
Laura D’Erasmo ◽  
Simone Bini ◽  
Marcello Arca
Keyword(s):  
Familial Hypercholesterolemia ◽  
Treatment Options ◽  
New Drugs ◽  
Lipid Lowering ◽  
Homozygous Familial Hypercholesterolemia ◽  
Published Evidence ◽  
Novel Drugs ◽  
Life Threatening ◽  
History Of ◽  
Definition Of

Abstract Purpose of Review This review aims to summarize the most recent published literature concerning lomitapide and volanesorsen that are approved for the use in HoFH and FCS patients, respectively. Moreover, it will briefly revise the published evidence on novel, non-approved treatments that are under evaluation for the management of these rare forms of dyslipidemias Recent Findings The definition of rare dyslipidemias identifies a large number of severe disorders of lipid metabolism of genetic origin. Among them were homozygous familial hypercholesterolemia (HoFH) (OMIM #143890) and familial chylomicronemia syndrome (FCS) (OMIM #238600), which are characterized by a markedly impaired cholesterol- and triglyceride-containing lipoproteins metabolism. They are being particularly associated with poor health outcomes and quality of life. Considering the severity of these diseases, common lipid-lowering drugs are often ineffective or do not allow to achieve the recommended lipid targets to prevent the development of complications. Nowadays, several new drugs have been found to effectively treat HoFH and FCS with an acceptable safety profile. Summary Treating patients with HoFH and FCS remains very challenging. However, novel treatment options are emerging and might be considered in addition to conventional therapy for managing these diseases. These novel drugs will possibly change the natural history of these two rare and life-threatening diseases.

Abstract 14407: The Longer-term Efficacy and Safety of Evinacumab in Patients With Homozygous Familial Hypercholesterolemia

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Frederick J Raal ◽  
Robert S Rosenson ◽  
Laurens F Reeskamp ◽  
G. Kees Hovingh ◽  
John J Kastelein ◽  
...  
Keyword(s):  
Familial Hypercholesterolemia ◽  
Treatment Period ◽  
Lipid Lowering ◽  
Efficacy And Safety ◽  
Homozygous Familial Hypercholesterolemia ◽  
Pcsk9 Inhibitors ◽  
Open Label ◽  
Phase 3 ◽  
Double Blind ◽  
Term Efficacy

Background: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic lipid disorder characterized by markedly elevated LDL-C and premature ASCVD. For HoFH patients (pts) with complete loss of low-density lipoprotein receptor (LDLR) function in both copies of the LDLR gene (null mutations) and some other HoFH pts, statins and PCSK9 inhibitors have limited to no efficacy, presenting a great unmet medical need. The efficacy and safety of evinacumab (EVIN; an angiopoietin-like protein 3 inhibitor) in HoFH pts was assessed during the double-blind treatment period (DBTP) of a phase 3 trial (NCT03399786). Objective: To examine longer-term efficacy and safety of EVIN in pts with HoFH who participated in the subsequent open-label treatment period (OLTP) of this phase 3 study. Methods: Patients with HoFH on stable lipid-lowering therapies (± lipoprotein apheresis) and screening LDL-C ≥70 mg/dL who completed the 24-week DBTP entered the 24-week OLTP and received IV EVIN 15 mg/kg every 4 weeks. Results: In total, 64 pts completed the DBTP and received open-label EVIN. Mean (standard deviation [SD]) baseline LDL-C at DBTP entry was 250.5 (162.3) mg/dL. From baseline to Week 48, EVIN reduced mean LDL-C by 46.3% (mean [SD] reduction of 134.3 [117.3] mg/dL). At Week 48, mean LDL-C reductions with open-label EVIN were 42.7% and 55.8% for pts who received EVIN (n=44) vs placebo (n=20) during the DBTP, respectively ( Figure ). LDL-C reduction observed at Week 48 was similar for pts with null/null mutations (n=19; 47.2%) versus non-null/null mutations (n=39; 45.9%). Adverse events (AEs) occurred in 47 pts (73.4%) during the OLTP; the most common were nasopharyngitis (9.4%) and headache (9.4%). During the OLTP, serious AEs occurred in 7 pts (10.9%; all pts received EVIN during the DBTP); none were considered related to study treatment. Conclusions: In pts with HoFH, EVIN showed substantial and sustained LDL-C reduction regardless of LDLR function and was generally well tolerated.

scholarly journals FP775CHILDREN WITH HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA (FH) ON LIPOPROTEIN APHERESIS − A FOUR YEAR FOLLOW−UP

2018 ◽  
Vol 33 (suppl_1) ◽  
pp. i306-i307
Author(s):  
Christina Taylan ◽  
Rasmus Ehren ◽  
Sandra Habbig ◽  
Kai Nuesken ◽  
Max Liebau ◽  
...  
Keyword(s):  
Familial Hypercholesterolemia ◽  
Homozygous Familial Hypercholesterolemia ◽  
Lipoprotein Apheresis

Burdern of Long-Term Morbidity after Hematopoietic Cell Transplantation: A Report from the Bone Marrow Transplant Survivor Study (BMTSS).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 832-832 ◽  
Author(s):  
Can-Lan Sun ◽  
Liton Francisco ◽  
Toana Kawashima ◽  
Leslie L. Robison ◽  
K.S. Baker ◽  
...  
Keyword(s):  
Health Condition ◽  
Chronic Health Conditions ◽  
Health Conditions ◽  
Unrelated Donor ◽  
Chronic Health ◽  
Threatening Condition ◽  
Life Threatening ◽  
Grade 3

Abstract Long-term survival is an expected outcome after HCT. However, no study has assessed the burden of long-term morbidity in these survivors, or attempted to identify subpopulations at highest risk for severe, debilitating conditions. In this study, we determined the prevalence and severity of chronic health conditions in a large population of long-term HCT survivors and compared these outcomes with their siblings. BMTSS, a collaborative effort between City of Hope National Medical Center and University of Minnesota, examined self-reported chronic health conditions in individuals who underwent HCT between 1976 and 1998, and survived two or more years. A severity score (grade 1 through 4, ranging from mild to life-threatening or disabling) was assigned to each health condition according to the Common Terminology Criteria for Adverse Events (version 3). A partial list of conditions graded as severe or life-threatening (grade 3 or 4) included congestive heart failure, second malignant neoplasms, coronary artery disease, cerebrovascular accident, renal failure/dialysis/renal transplant, and active chronic graft vs. host disease. Adverse psychosocial outcomes were not included. Cox proportional-hazard models were used to estimate hazard ratios and their 95% confidence intervals. We compared the prevalence and severity of chronic conditions in 1013 HCT survivors (455 autologous, 460 related donor, and 98 unrelated donor HCT survivors) with 309 siblings. The median age at study participation was 44 (range 18–73) and 45 years (range 17–79) for survivors and siblings, and the median follow-up for the survivors was 7.3 years (range 2–28) from HCT. Among the 1013 survivors, 69% had at least one chronic condition, and 29% had a severe or life-threatening condition (grade 3 or 4). The comparable figures in siblings were 39% and 7%, respectively (p<0.001 compared to survivors). After adjustment for age at HCT, sex and race/ethnicity, survivors were 2.4 times as likely as their siblings to develop any chronic health conditions (95%CI, 2.0–2.9), and 4.5 times more likely to develop severe/life threatening conditions (95%CI, 3.0–6.7). Groups at highest risk for a severe or life-threatening condition are summarized in the Table. Among survivors, the cumulative incidence of a chronic health condition reached 84% at 20 years post HCT, with a cumulative incidence of 55% for severe/life threatening conditions at 15 years after HCT. The chronic health burden of this population is significant, and life-long follow-up of patients who receive transplantation is recommended. Table: Groups at highest risk for severe or life-threatening condition Risk Factors Relative Risk 95% CI Siblings 1.0 __ CML 5.8 3.8–8.9 AML 4.9 3.2–7.5 ALL 5.2 3.3–8.3 Allogeneic sibling donor 5.9 3.9–8.7 Unrelated donor 7.4 4.9–11.1 TBI 5.0 3.4–7.5

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