Lipid-Reduction Variability and Antidrug-Antibody Formation with Bococizumab
| Autor: | Ridker, P.M., Tardif, J.C., Amarenco, P., Duggan, W., Glynn, R.J., Jukema, J.W., Kastelein, J.J.P., Kim, A.M., Koenig, W., Nissen, S., Revkin, J., Rose, L.M., Santos, R.D., Schwartz, P.F., Shear, C.L., Yunis, C., SPIRE Investigators |
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| Přispěvatelé: | Vascular Medicine, ACS - Amsterdam Cardiovascular Sciences, ACS - Pulmonary hypertension & thrombosis, ACS - Atherosclerosis & ischemic syndromes |
| Rok vydání: | 2017 |
| Předmět: |
Male
medicine.medical_specialty medicine.drug_class Injections Subcutaneous Hypercholesterolemia 030204 cardiovascular system & hematology Bococizumab Monoclonal antibody Placebo Antibodies Monoclonal Humanized Gastroenterology Antibodies 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine Hyperlipidemia medicine Humans 030212 general & internal medicine biology Cholesterol business.industry PCSK9 Anticholesteremic Agents PCSK9 Inhibitors General Medicine Cholesterol LDL Middle Aged medicine.disease Lipids Endocrinology Treatment Outcome chemistry biology.protein lipids (amino acids peptides and proteins) Female Antibody Proprotein Convertase 9 business Lipoprotein Follow-Up Studies |
| Zdroj: | New England Journal of Medicine, 376(16), 1517-1526 New England journal of medicine, 376(16), 1517-1526. Massachussetts Medical Society |
| ISSN: | 1533-4406 0028-4793 |
| Popis: | Bococizumab, a humanized monoclonal antibody targeting proprotein convertase subtilisin-kexin type 9 (PCSK9), reduces levels of low-density lipoprotein (LDL) cholesterol. However, the variability and durability of this effect are uncertain.We conducted six parallel, multinational lipid-lowering trials enrolling 4300 patients with hyperlipidemia who were randomly assigned to receive 150 mg of bococizumab or placebo subcutaneously every 2 weeks and who were followed for up to 12 months; 96% were receiving statin therapy at the time of enrollment. The patients were assessed for lipid changes over time, stratified according to the presence or absence of antidrug antibodies detected during the treatment period.At 12 weeks, patients who received bococizumab had a reduction of 54.2% in the LDL cholesterol level from baseline, as compared with an increase of 1.0% among those who received placebo (absolute between-group difference, -55.2 percentage points). Significant between-group differences were also observed in total cholesterol, non-high-density lipoprotein cholesterol, apolipoprotein B, and lipoprotein(a) (P0.001 for all comparisons). However, high-titer antidrug antibodies developed in a substantial proportion of the patients who received bococizumab, which markedly diminished the magnitude and durability of the reduction in LDL cholesterol levels. In addition, among patients with no antidrug antibodies, there was wide variability in the reduction in LDL cholesterol levels at both 12 weeks and 52 weeks. Major cardiovascular events occurred in 57 patients (2.5%) who received bococizumab and in 55 (2.7%) who received placebo (hazard ratio, 0.96; 95% confidence interval, 0.66 to 1.39; P=0.83). The most common adverse event among patients who received bococizumab was injection-site reaction (12.7 per 100 person-years).In six multinational trials evaluating bococizumab, antidrug antibodies developed in a large proportion of the patients and significantly attenuated the lowering of LDL cholesterol levels. Wide variation in the relative reduction in cholesterol levels was also observed among patients in whom antidrug antibodies did not develop. (Funded by Pfizer; SPIRE ClinicalTrials.gov numbers, NCT01968954 , NCT01968967 , NCT01968980 , NCT02100514 , NCT02135029 , and NCT02458287 .). |
| Databáze: | OpenAIRE |
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