{"id":"869c148b24db","type":"article","url":"https://hartvaat.nl/2017/04/20/ldl-reductievariabiliteit-en-antilichaamvorming-bij-bococizumab-nejm/","title":"LDL-reductievariabiliteit en antilichaamvorming bij bococizumab: NEJM","title_en":"Lipid-Reduction Variability and Antidrug-Antibody Formation with Bococizumab.","category":"cholesterol","category_label":"Cholesterol","professions":["apotheker","cardioloog","internist"],"tags":["bempedoïnezuur","cetp-remmers","ezetimibe","lipidenverlaging","niet-statine-therapie","obicetrapib","pcsk9-remmers","pcsk9-remmers-nieuwe-generatie","statines"],"journal":"The New England journal of medicine","doi":"10.1056/NEJMoa1614062","source_url":"https://doi.org/10.1056/NEJMoa1614062","authors":["Paul M Ridker","Jean-Claude Tardif","Pierre Amarenco","William Duggan","Robert J Glynn","J Wouter Jukema","John J P Kastelein","Albert M Kim","Wolfgang Koenig","Steven Nissen","James Revkin","Lynda M Rose","Raul D Santos","Pamela F Schwartz","Charles L Shear","Carla Yunis"],"significance":8,"published":"2017-04-20","source_date":"2017-04-20","image":"","kennis":["https://hartvaat.nl/kennis/lipiden/ldl-cholesterol-mechanisme/"],"congress":"","summary_en":"This NEJM study showed that bococizumab, a humanized PCSK9 monoclonal antibody, triggered anti-drug antibody formation that progressively attenuated its LDL-lowering effect. The immunogenicity issue led to the drug's discontinuation and highlighted the advantage of fully human antibodies like evolocumab and alirocumab.","created":"2026-07-03T10:26:40Z","updated":"2026-07-03T13:25:58Z","licence":"Citeer vrij, met bronvermelding en een link naar hartvaat.nl (de url van het record). Samenvattingen zijn redactioneel werk van HartVaat; de oorspronkelijke publicaties blijven van hun uitgevers (doi). Geen medisch advies.","body_markdown":"NEJM-studie die aantoonde dat bococizumab (PCSK9-remmer) leidt tot antilichaamvorming met afnemende werkzaamheid. Een van de redenen voor het stopzetten van het bococizumab-programma.","abstract_original":"BACKGROUND: 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. METHODS: 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. RESULTS: 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) (P<0.001 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). CONCLUSIONS: 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 .)."}