Lipid-reduction variability and antidrug-antibody formation with bococizumab
Open accessAbstract
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 .).
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Both alirocumab and evolocumab effectively lower LDL-C in high cardiovascular risk patients, including those with diabetes mellitus.
“Both alirocumab and evolocumab have also been shown to effectively lower LDL-C levels in patients who are at high CV risk, including those with DM [284].”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [284]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Rosuvastatin to Prevent Vascular Events in Men and Women with Elevated C-Reactive Protein
Ridker, P. M., Danielson, E., Fonseca, F. A. H., Genest, J., Gotto, A. M., Kastelein, J. J. P., Koenig, W., Libby, P., Lorenzatti, A. J., MacFadyen, J. G., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0807646 · Cited by 6,674 · see citing works
Self-citationEzetimibe Added to Statin Therapy after Acute Coronary Syndromes
Cannon, C. P., Blazing, M. A., Giugliano, R. P., McCagg, A., White, J. A., Theroux, P., Darius, H., Lewis, B. S., Ophuis, T. O., Jukema, J. W., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1410489 · Cited by 4,487 · see citing works
Self-citationCollaborators, C. T. T. (. (2012) · The Lancet · doi:10.1016/s0140-6736(12)60367-5 · Cited by 2,833 · see citing works
Efficacy and Safety of Alirocumab in Reducing Lipids and Cardiovascular Events
Robinson, J. G., Farnier, M., Krempf, M., Bergeron, J., Luc, G., Averna, M., Stroes, E. S., Langslet, G., Raal, F. J., El Shahawy, M., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1501031 · Cited by 2,296 · see citing works
Self-citationEfficacy and Safety of Evolocumab in Reducing Lipids and Cardiovascular Events
Sabatine, M. S., Giugliano, R. P., Wiviott, S. D., Raal, F. J., Blom, D. J., Robinson, J., Ballantyne, C. M., Somaratne, R., Legg, J., Wasserman, S. M., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1500858 · Cited by 1,509 · see citing works
Ference, B. A., Yoo, W., Alesh, I., Mahajan, N., Mirowska, K. K., Mewada, A., Kahn, J., Afonso, L., Williams, K. A., & Flack, J. M. (2012) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2012.09.017 · Cited by 898 · see citing works
The biology and therapeutic targeting of the proprotein convertases
Seidah, N. G., & Prat, A. (2012) · Nature Reviews Drug Discovery · doi:10.1038/nrd3699 · Cited by 819 · see citing works
Cardiovascular Efficacy and Safety of Bococizumab in High-Risk Patients
Ridker, P. M., Revkin, J., Amarenco, P., Brunell, R., Curto, M., Civeira, F., Flather, M., Glynn, R. J., Gregoire, J., Jukema, J. W., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1701488 · Cited by 624 · see citing works
Self-citationVery Low Levels of Atherogenic Lipoproteins and the Risk for Cardiovascular Events
Boekholdt, S. M., Hovingh, G. K., Mora, S., Arsenault, B. J., Amarenco, P., Pedersen, T. R., LaRosa, J. C., Waters, D. D., DeMicco, D. A., Simes, R. J., et al. (2014) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2014.02.615 · Cited by 581 · see citing works
Self-citationRidker, P. M., Mora, S., & Rose, L. M. (2016) · European Heart Journal · doi:10.1093/eurheartj/ehw046 · Cited by 222 · see citing works
Self-citationBallantyne, C. M., Neutel, J., Cropp, A., Duggan, W. T., Wang, E. Q., Plowchalk, D. R., Sweeney, K., Kaila, N., Vincent, J., & Bays, H. E. (2015) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2015.02.006 · Cited by 170 · see citing works
Self-citationEvolution and Emergence of Therapeutic Monoclonal Antibodies
Foltz, I. N., Karow, M. L., & Wasserman, S. M. (2013) · Circulation · doi:10.1161/circulationaha.113.002033 · Cited by 99 · see citing works
Antidrug Antibodies in Patients Treated with Alirocumab
Roth, E. M., Goldberg, A. C., Catapano, A. L., Torri, A., Yancopoulos, G. D., Stahl, N., Brunet, A., Lecorps, G., & Colhoun, H. M. (2017) · New England Journal of Medicine · doi:10.1056/nejmc1616623 · Cited by 90 · see citing works
Ridker, P. M., Amarenco, P., Brunell, R., Glynn, R. J., Jukema, J. W., Kastelein, J. J. P., Köenig, W., Nissen, S. E., Revkin, J. H., Santos, R. D., et al. (2016) · American Heart Journal · doi:10.1016/j.ahj.2016.05.010 · Cited by 62 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Mach, F., Baigent, C., Catapano, A. L., Koskinas, K. C., Casula, M., Badimon, L., Chapman, M. J., De Backer, G. G., Delgado, V., Ference, B. A., et al. (2019) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2019.08.014 · Cited by 4,854 · see citing works
Inclisiran for the Treatment of Heterozygous Familial Hypercholesterolemia
Raal, F. J., Kallend, D., Ray, K. K., Turner, T., Koenig, W., Wright, R. S., Wijngaard, P. L. J., Curcio, D., Jaros, M. J., Leiter, L. A., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa1913805 · Cited by 818 · see citing works
Self-citationNext generation antibody drugs: pursuit of the 'high-hanging fruit'
Carter, P. J., & Lazar, G. A. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.227 · Cited by 760 · see citing works
Cardiovascular Efficacy and Safety of Bococizumab in High-Risk Patients
Ridker, P. M., Revkin, J., Amarenco, P., Brunell, R., Curto, M., Civeira, F., Flather, M., Glynn, R. J., Gregoire, J., Jukema, J. W., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1701488 · Cited by 624 · see citing works
Self-citationLloyd‐Jones, D. M., Morris, P. B., Ballantyne, C. M., Birtcher, K. K., Daly, D. D., DePalma, S. M., Minissian, M., Orringer, C. E., & Smith, S. C. (2017) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2017.07.745 · Cited by 383 · see citing works
PCSK9 inhibitors: clinical evidence and implementation
Sabatine, M. S. (2018) · Nature Reviews Cardiology · doi:10.1038/s41569-018-0107-8 · Cited by 363 · see citing works
PCSK9: From Basic Science Discoveries to Clinical Trials
Shapiro, M. D., Tavori, H., & Fazio, S. (2018) · Circulation Research · doi:10.1161/circresaha.118.311227 · Cited by 285 · see citing works
Designing antibodies as therapeutics
Carter, P. J., & Rajpal, A. (2022) · Cell · doi:10.1016/j.cell.2022.05.029 · Cited by 275 · see citing works
Residual Inflammatory Risk on Treatment With PCSK9 Inhibition and Statin Therapy
Pradhan, A. D., Aday, A. W., Rose, L. M., & Ridker, P. M. (2018) · Circulation · doi:10.1161/circulationaha.118.034645 · Cited by 258 · see citing works
Self-citationThe Evolving Future of PCSK9 Inhibitors
Rosenson, R. S., Hegele, R. A., Fazio, S., & Cannon, C. P. (2018) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2018.04.054 · Cited by 264 · see citing works
Cholesterol transport system: An integrated cholesterol transport model involved in atherosclerosis.
Yu, X.-H., Zhang, D.-W., Zheng, X.-L., & Tang, C.-K. (2019) · Progress in lipid research · doi:10.1016/j.plipres.2018.12.002 · Cited by 179 · see citing works
PCSK9 monoclonal antibodies for the primary and secondary prevention of cardiovascular disease
Schmidt, A. F., Pearce, L. S., Wilkins, J. T., Overington, J. P., Hingorani, A. D., & Casas, J. P. (2017) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd011748.pub2 · Cited by 202 · see citing works
Landmesser, U., Chapman, M. J., Stock, J. K., Amarenco, P., Belch, J. J. F., Borén, J., Farnier, M., Ference, B. A., Gielen, S., Graham, I., et al. (2018) · European Heart Journal · doi:10.1093/eurheartj/ehx549 · Cited by 200 · see citing works
Self-citationHolmes, M. V., Richardson, T. G., Ference, B. A., Davies, N. M., & Davey Smith, G. (2021) · Nature Reviews Cardiology · doi:10.1038/s41569-020-00493-1 · Cited by 184 · see citing works
Immunogenicity of Protein Pharmaceuticals
Dingman, R. K., & Balu‐Iyer, S. V. (2018) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2018.12.014 · Cited by 157 · see citing works
Ray, K. K., Stoekenbroek, R. M., Kallend, D., Leiter, L. A., Landmesser, U., Wright, R. S., Wijngaard, P., & Kastelein, J. J. P. (2018) · Circulation · doi:10.1161/circulationaha.118.034710 · Cited by 154 · see citing works
Self-citationImmunogenicity assessment during the development of protein therapeutics
Rosenberg, A. S., & Sauna, Z. E. (2018) · Journal of Pharmacy and Pharmacology · doi:10.1111/jphp.12810 · Cited by 131 · see citing works
Lipid lowering therapy and circulating PCSK9 concentration
Nozue, T. (2017) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.rv17012 · Cited by 127 · see citing works
Mhaimeed, O., Burney, Z. A., Schott, S. L., Kohli, P., Marvel, F. A., & Martin, S. S. (2024) · American Journal of Preventive Cardiology · doi:10.1016/j.ajpc.2024.100649 · Cited by 136 · see citing works
Mach, F., Baigent, C., Catapano, A. L., Koskinas, K. C., Casula, M., Badimon, L., Chapman, M. J., De Backer, G. G., Delgado, V., Ference, B. A., et al. (2020) · European Heart Journal · doi:10.1093/eurheartj/ehz455 · Cited by 8,961 · see citing works
PCSK9 monoclonal antibodies for the primary and secondary prevention of cardiovascular disease
Schmidt, A. F., Carter, J.-P. L., Pearce, L. S., Wilkins, J. T., Overington, J. P., Hingorani, A. D., & Casas, J. (2020) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd011748.pub3 · Cited by 123 · see citing works
Neutralizing Anti-Rituximab Antibodies and Relapse in Membranous Nephropathy Treated With Rituximab
Boyer‐Suavet, S., Andreani, M., Lateb, M., Savenkoff, B., Brglez, V., Benzaken, S., Bernard, G., Nachman, P. H., Esnault, V. L. M., & Seitz‐Polski, B. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2019.03069 · Cited by 126 · see citing works
Inclisiran—New hope in the management of lipid disorders?
Dyrbuś, K., Gąsior, M., Penson, P., Ray, K. K., & Banach, M. (2020) · Journal of Clinical Lipidology · doi:10.1016/j.jacl.2019.11.001 · Cited by 120 · see citing works
Evaluating and mitigating the immunogenicity of therapeutic proteins
Sauna, Z. E., Lagassé, D., Pedras-Vasconcelos, J., Golding, B., & Rosenberg, A. S. (2018) · Trends in biotechnology · doi:10.1016/j.tibtech.2018.05.008 · Cited by 118 · see citing works
Davis, J. D., Padros, M. B., Conrado, D. J., Ganguly, S., Guan, X., Hassan, H. E., Hazra, A., Irvin, S. C., Jayachandran, P., Kosloski, M. P., et al. (2023) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.3150 · Cited by 119 · see citing works
Lu, Y., Cui, X., Zhang, L., Wang, X., Xu, Y., Qin, Z., Liu, G., Wang, Q., Tian, K., Lim, K. S., et al. (2022) · Aging and Disease · doi:10.14336/ad.2021.0929 · Cited by 114 · see citing works
Immunogenicity risk assessment and mitigation for engineered antibody and protein therapeutics
Carter, P. J., & Quarmby, V. E. (2024) · Nature Reviews Drug Discovery · doi:10.1038/s41573-024-01051-x · Cited by 114 · see citing works
Small Interfering RNA Therapeutic Inclisiran: A New Approach to Targeting PCSK9
German, C. A., & Shapiro, M. D. (2019) · BioDrugs · doi:10.1007/s40259-019-00399-6 · Cited by 115 · see citing works
Established and Emerging Lipid-Lowering Drugs for Primary and Secondary Cardiovascular Prevention
Michaeli, D. T., Michaeli, J. C., Albers, S., Boch, T., & Michaeli, T. (2023) · American Journal of Cardiovascular Drugs · doi:10.1007/s40256-023-00594-5 · Cited by 109 · see citing works
“PCSK9 inhibitors were also discussed to induce the expression of auto-antibodies and increase the risk of diabetes mellitus [89, 90].”
BackgroundMark, H. (2017) · doi:10.1016/j.jacc.2017.10.001 · Cited by 107 · see citing works
The PCSK9 revolution: Current status, controversies, and future directions
Warden, B. A., Fazio, S., & Shapiro, M. D. (2019) · Trends in Cardiovascular Medicine · doi:10.1016/j.tcm.2019.05.007 · Cited by 100 · see citing works
Chen, E., Chuang, L.-S. F., Giri, M., Villaverde, N., Hsu, N.-Y., Sabic, K., Joshowitz, S., Gettler, K., Nayar, S., Chai, Z., et al. (2021) · Gastroenterology · doi:10.1053/j.gastro.2020.12.076 · Cited by 100 · see citing works
Meta-Analysis of Inclisiran for the Treatment of Hypercholesterolemia
Khan, S. A., Naz, A., Qamar Masood, M., & Shah, R. (2020) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2020.08.018 · Cited by 98 · see citing works
Pratt, K. P. (2018) · Antibodies · doi:10.3390/antib7020019 · Cited by 96 · see citing works
A Comprehensive Review of PCSK9 Inhibitors
Coppinger, C., Movahed, M. R., Azemawah, V., Peyton, L., Gregory, J., & Hashemzadeh, M. (2022) · Journal of Cardiovascular Pharmacology and Therapeutics · doi:10.1177/10742484221100107 · Cited by 99 · see citing works
Physiological and therapeutic regulation of PCSK9 activity in cardiovascular disease
Glerup, S., Schulz, R., Laufs, U., & Schlüter, K. (2017) · Basic Research in Cardiology · doi:10.1007/s00395-017-0619-0 · Cited by 92 · see citing works
Antidrug Antibodies in Patients Treated with Alirocumab
Roth, E. M., Goldberg, A. C., Catapano, A. L., Torri, A., Yancopoulos, G. D., Stahl, N., Brunet, A., Lecorps, G., & Colhoun, H. M. (2017) · New England Journal of Medicine · doi:10.1056/nejmc1616623 · Cited by 90 · see citing works
Fifty years of monoclonals: the past, present and future of antibody therapeutics
Chan, A. C., Martyn, G. D., & Carter, P. J. (2025) · Nature reviews. Immunology · doi:10.1038/s41577-025-01207-9 · Cited by 96 · see citing works
PCSK9 Inhibition: Insights From Clinical Trials and Future Prospects
Katzmann, J. L., Gouni‐Berthold, I., & Laufs, U. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.595819 · Cited by 89 · see citing works
Gragnano, F., & Calabrò, P. (2018) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2018.01.012 · Cited by 87 · see citing works
PCSK9 inhibitors for treating hypercholesterolemia
Pasta, A., Cremonini, A. L., Pisciotta, L., Buscaglia, A., Porto, I., Barra, F., Ferrero, S., Brunelli, C., & Rosa, G. M. (2020) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2019.1702970 · Cited by 87 · see citing works
Nutraceuticals as therapeutic agents for atherosclerosis
Moss, J. W. E., Williams, J. O., & Ramji, D. P. (2018) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2018.02.006 · Cited by 85 · see citing works
PCSK9 Inhibitors: Mechanisms of Action, Metabolic Effects, and Clinical Outcomes
Hess, C. N., Wang, C. C. L., & Hiatt, W. R. (2017) · Annual Review of Medicine · doi:10.1146/annurev-med-042716-091351 · Cited by 84 · see citing works
Cunningham, O., Scott, M. J., Zhou, Z., & Finlay, W. J. J. (2021) · mAbs · doi:10.1080/19420862.2021.1999195 · Cited by 72 · see citing works
Lipid-Modifying Agents, From Statins to PCSK9 Inhibitors
Preiss, D., Tobert, J. A., Hovingh, G. K., & Reith, C. (2020) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2019.11.072 · Cited by 75 · see citing works
Zhang, W., Wang, H., Feng, N., Li, Y., Gu, J., & Wang, Z. (2022) · Antibody Therapeutics · doi:10.1093/abt/tbac029 · Cited by 74 · see citing works
Dyson, M. R., Masters, E. W., Pazeraitis, D., Perera, R. L., Syrjänen, J. L., Surade, S. B., Thorsteinson, N., Parthiban, K., Jones, P. C., Sattar, M., et al. (2020) · mAbs · doi:10.1080/19420862.2020.1829335 · Cited by 68 · see citing works
Advances in biological therapies for dyslipidemias and atherosclerosis
Valanti, E.-K., Dalakoura-Karagkouni, K., Siasos, G., Kardassis, D., Eliopoulos, A. G., & Sanoudou, D. (2020) · Metabolism · doi:10.1016/j.metabol.2020.154461 · Cited by 68 · see citing works
Wang, X., Wen, D., Chen, Y., Ma, L., & You, C. (2022) · Cardiovascular Diabetology · doi:10.1186/s12933-022-01542-4 · Cited by 67 · see citing works
Inclisiran: a novel agent for lowering apolipoprotein B–containing lipoproteins
Warden, B. A., & Duell, P. B. (2021) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0000000000001053 · Cited by 62 · see citing works
Lipid Management in Patients Presenting With Acute Coronary Syndromes: A Review
Claessen, B. E. P. M., Guedeney, P., Gibson, C. M., Angiolillo, D. J., Cao, D., Lepor, N. E., & Mehran, R. (2020) · Journal of the American Heart Association · doi:10.1161/jaha.120.018897 · Cited by 65 · see citing works
Guedeney, P., Sorrentino, S., Giustino, G., Chapelle, C., Laporte, S., Claessen, B. E. P. M., Ollier, É., Camaj, A., Kalkman, D. N., Vogel, B., et al. (2020) · European Heart Journal - Cardiovascular Pharmacotherapy · doi:10.1093/ehjcvp/pvaa024 · Cited by 64 · see citing works
Development of ImmTOR Tolerogenic Nanoparticles for the Mitigation of Anti-drug Antibodies
Kishimoto, T. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00969 · Cited by 63 · see citing works
New Pharmacological Approaches to Target PCSK9
Catapano, A. L., Pirillo, A., & Norata, G. D. (2020) · Current Atherosclerosis Reports · doi:10.1007/s11883-020-00847-7 · Cited by 61 · see citing works
Sands, E., Kivitz, A., DeHaan, W., Leung, S. S., Johnston, L., & Kishimoto, T. K. (2022) · Nature Communications · doi:10.1038/s41467-021-27945-7 · Cited by 61 · see citing works
Interindividual Variation in Low-Density Lipoprotein Cholesterol Level Reduction With Evolocumab
Qamar, A., Giugliano, R. P., KEECH, A. C., Kuder, J., Murphy, S. A., Kurtz, C. E., Wasserman, S. M., Sever, P. S., Pedersen, T. R., & Sabatine, M. S. (2018) · JAMA Cardiology · doi:10.1001/jamacardio.2018.4178 · Cited by 61 · see citing works
Hu, B., Boakye‐Yiadom, K. O., Yu, W., Yuan, Z., Ho, W., Xu, X., & Zhang, X. (2020) · Advanced Healthcare Materials · doi:10.1002/adhm.202000336 · Cited by 62 · see citing works
Ridker, P. M., Rose, L. M., Kastelein, J. J. P., Santos, R. D., Wei, C., Revkin, J. H., Yunis, C., Tardif, J., & Shear, C. L. (2018) · Journal of clinical lipidology · doi:10.1016/j.jacl.2018.03.088 · Cited by 60 · see citing works
Self-citationSingh, S. K., Mahler, H., Hartman, C., & Stark, C. A. (2018) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2018.07.016 · Cited by 60 · see citing works
Farnier, M., Hovingh, G. K., Langslet, G., Dufour, R., Baccara‐Dinet, M. T., Din-Bell, C., Manvelian, G. Z., & Guyton, J. R. (2018) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2018.08.036 · Cited by 58 · see citing works
Targeted Strategy in Lipid-Lowering Therapy
Dayar, E., & Pecháňová, O. (2022) · Biomedicines · doi:10.3390/biomedicines10051090 · Cited by 59 · see citing works
Familial Hypercholesterolemia: New Horizons for Diagnosis and Effective Management
Mytilinaiou, M. G., Kyrou, I., Khan, M., Grammatopoulos, D. K., & Randeva, H. S. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.00707 · Cited by 59 · see citing works
Development of small-molecule PCSK9 inhibitors for the treatment of hypercholesterolemia.
Ahamad, S., Mathew, S., Khan, W. A., & Mohanan, K. (2022) · Drug Discovery Today · doi:10.1016/j.drudis.2022.01.014 · Cited by 44 · see citing works
Inclisiran for the treatment of dyslipidemia
Nishikido, T., & Ray, K. K. (2018) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2018.1442435 · Cited by 56 · see citing works
Safety of recombinant human hyaluronidase PH20 for subcutaneous drug delivery
Knowles, S. P., Printz, M. A., Kang, D. W., LaBarre, M. J., & Tannenbaum, R. P. (2021) · Expert Opinion on Drug Delivery · doi:10.1080/17425247.2021.1981286 · Cited by 54 · see citing works
Low LDL cholesterol by PCSK9 variation reduces cardiovascular mortality
Benn, M., Tybjærg-Hansen, A., & Nordestgaard, B. G. (2019) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2019.03.517 · Cited by 51 · see citing works
Meta‐analysis of clinical outcomes of PCSK9 modulators in patients with established ASCVD
Talasaz, A. H., Ho, A. (., Bhatty, F., Koenig, R. A., Dixon, D. L., Baker, W. L., & Van Tassell, B. W. (2021) · Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy · doi:10.1002/phar.2635 · Cited by 48 · see citing works
Safety and tolerability of injectable lipid-lowering drugs: an update of clinical data
Strilchuk, L. M., Fogacci, F., & Cicero, A. F. G. (2019) · Expert Opinion on Drug Safety · doi:10.1080/14740338.2019.1620730 · Cited by 48 · see citing works
Adair, P., Kim, Y. C., Zhang, A.-H., Yoon, J., & Scott, D. W. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01117 · Cited by 44 · see citing works
PCSK9: from biology to clinical applications
Blanchard, V., Khantalin, I., Ramin‐Mangata, S., Chemello, K., Nativel, B., & Lambert, G. C. (2018) · Pathology · doi:10.1016/j.pathol.2018.10.012 · Cited by 45 · see citing works
Khoury, P. E., Elbitar, S., Ghaleb, Y., Khalil, Y. A., Varret, M., Boileau, C., & Abifadel, M. (2017) · Current Atherosclerosis Reports · doi:10.1007/s11883-017-0684-8 · Cited by 42 · see citing works
Casula, M., Olmastroni, E., Boccalari, M. T., Tragni, E., Pirillo, A., & Catapano, A. L. (2019) · Pharmacological Research · doi:10.1016/j.phrs.2019.03.021 · Cited by 42 · see citing works
The evolving landscape of PCSK9 inhibition in cancer
Oza, P. P., & Kashfi, K. (2023) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2023.175721 · Cited by 42 · see citing works
Sun, R., Qian, M. G., & Zhang, X. (2024) · mAbs · doi:10.1080/19420862.2024.2324836 · Cited by 44 · see citing works
Plant Viruses and Bacteriophage-Based Reagents for Diagnosis and Therapy
Shukla, S., Hu, H., Cai, H., Chan, S. K., Boone, C. E., Beiss, V., Chariou, P. L., & Steinmetz, N. F. (2020) · Annual Review of Virology · doi:10.1146/annurev-virology-010720-052252 · Cited by 40 · see citing works
PCSK9 inhibitors: current status and emerging frontiers in lipid control
Agnello, F. G., Mauro, M. S., Rochira, C., Landolina, D., Finocchiaro, S., Greco, A., Ammirabile, N., Raffo, C., Mazzone, P. M., Spagnolo, M., et al. (2023) · Expert Review of Cardiovascular Therapy · doi:10.1080/14779072.2023.2288169 · Cited by 40 · see citing works
Quarmby, V. E., Phung, Q. T., & Lill, J. R. (2018) · Expert Review of Proteomics · doi:10.1080/14789450.2018.1521279 · Cited by 37 · see citing works
Cohen, S., Myneni, S., Batt, A. R., Guerrero, J., Brumm, J., & Chung, S. (2021) · mAbs · doi:10.1080/19420862.2021.1898831 · Cited by 37 · see citing works
Chasing LDL cholesterol to the bottom — PCSK9 in perspective
Libby, P., & Tokgözoğlu, L. S. (2022) · Nature Cardiovascular Research · doi:10.1038/s44161-022-00085-x · Cited by 38 · see citing works
Garwood, C. L., Cabral, K. P., Brown, R., & Dixon, D. L. (2024) · Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy · doi:10.1002/phar.4635 · Cited by 44 · see citing works
Efficacy and Safety of Alirocumab Versus Ezetimibe Over 2 Years (from ODYSSEY COMBO II)
Shahawy, M. E., Cannon, C. P., Blom, D. J., McKenney, J. M., Cariou, B., Lecorps, G., Pordy, R. C., Chaudhari, U., & Colhoun, H. M. (2017) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2017.06.023 · Cited by 36 · see citing works
Shores, L. S., Kelly, S. H., Hainline, K. M., Suwanpradid, J., MacLeod, A. S., & Collier, J. H. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01855 · Cited by 36 · see citing works
Arca, M., Celant, S., Olimpieri, P. P., Colatrella, A., Tomassini, L., D'Erasmo, L., Averna, M., Zambon, A., Catapano, A. L., & Russo, P. (2023) · Journal of the American Heart Association · doi:10.1161/jaha.122.026550 · Cited by 35 · see citing works
PCSK9 in cholesterol metabolism: from bench to bedside
Reiss, A. B., Shah, N. B., Muhieddine, D., Zhen, J., Yudkevich, J., Kasselman, L. J., & DeLeon, J. R. (2018) · Clinical Science · doi:10.1042/cs20180190 · Cited by 35 · see citing works
Du, H., Li, X., Su, N., Li, L., Hao, X., Gao, H., Kwong, J. S.-W., Vandvik, P. O., Yang, X., Németh, I., et al. (2019) · Heart · doi:10.1136/heartjnl-2019-314763 · Cited by 35 · see citing works
Hepatic Sensing Loop Regulates PCSK9 Secretion in Response to Inhibitory Antibodies
Oleaga, C., Shapiro, M. D., Hay, J., Mueller, P. A., Miles, J., Huang, C., Friz, E., Tavori, H., Toth, P. P., Wójcik, C., et al. (2021) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2021.07.056 · Cited by 35 · see citing works
Lipid-Lowering Drug Therapy: Critical Approach for Implementation in Clinical Practice
Rossi, M., Fabris, E., Barbisan, D., Massa, L., & Sinagra, G. (2021) · American Journal of Cardiovascular Drugs · doi:10.1007/s40256-021-00497-3 · Cited by 35 · see citing works
MK-0616: an oral PCSK9 inhibitor for hypercholesterolemia treatment
Burnett, J. R., & Hooper, A. J. (2023) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2023.2267972 · Cited by 34 · see citing works
Baragetti, A., Grejtáková, D., Casula, M., Olmastroni, E., Jotti, G. S., Norata, G. D., Catapano, A. L., & Bellosta, S. (2018) · Pharmacological Research · doi:10.1016/j.phrs.2018.01.025 · Cited by 34 · see citing works
Individualized Dosing of Therapeutic Monoclonal Antibodies—a Changing Treatment Paradigm?
Strik, A. S., Wang, Y., Ruff, L. E., Yashar, W. M., Messmer, B. T., & Mould, D. R. (2018) · The AAPS Journal · doi:10.1208/s12248-018-0257-y · Cited by 34 · see citing works
Mu, G., Xiang, Q., Zhou, S., Liu, Z., Qi, L., Jiang, J., Gong, Y., Xie, Q., Wang, Z., Zhang, H., et al. (2020) · Advances in Therapy · doi:10.1007/s12325-020-01259-4 · Cited by 33 · see citing works
Role of PCSK9 Inhibitors in Patients with Familial Hypercholesterolemia
Tomlinson, B., Patil, N. G., Fok, M., & Lam, C. W. K. (2021) · Endocrinology and Metabolism · doi:10.3803/enm.2021.964 · Cited by 34 · see citing works
Biology, pathophysiology and current therapies that affect lipoprotein (a) levels
Rawther, T., & Tabet, F. (2019) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2019.04.005 · Cited by 31 · see citing works
PCSK9 inhibition and atherosclerotic cardiovascular disease prevention: does reality match the hype?
Hadjiphilippou, S., & Ray, K. K. (2017) · Heart · doi:10.1136/heartjnl-2016-310844 · Cited by 30 · see citing works
Müller‐Wieland, D., Leiter, L. A., Cariou, B., Letierce, A., Colhoun, H. M., Prato, S. D., Henry, R. R., Tinahones, F. J., Aurand, L. A., Maroni, J. M., et al. (2017) · Cardiovascular Diabetology · doi:10.1186/s12933-017-0552-4 · Cited by 30 · see citing works
Kimball, A. B., Kerbusch, T., van Aarle, F., Kulkarni, P., Li, Q., Blauvelt, A., Papp, K. A., Reich, K., & Montgomery, D. L. (2019) · British Journal of Dermatology · doi:10.1111/bjd.17918 · Cited by 30 · see citing works
Duke, B. R., & Mitra‐Kaushik, S. (2019) · Journal of Pharmaceutical Innovation · doi:10.1007/s12247-019-09412-5 · Cited by 30 · see citing works
Cordero, A., Rodríguez‐Mañero, M., Fácila, L., Fernández-Olmo, M. R., Gómez-Martínez, M. J., Valle, A., Castellano, J. M., Toro, M. M., Seijas‐Amigo, J., Vicedo-López, Á., et al. (2020) · Journal of Diabetes & Metabolic Disorders · doi:10.1007/s40200-020-00557-6 · Cited by 30 · see citing works
Efficacy and safety of PCSK9 monoclonal antibodies: an evidence-based review and update
Kaddoura, R., Orabi, B., & Salam, A. M. (2020) · Journal of Drug Assessment · doi:10.1080/21556660.2020.1801452 · Cited by 30 · see citing works
Estimation of the major cardiovascular events prevention with Inclisiran
Cordero, A., Santos‐Gallego, C. G., Fácila, L., Rodríguez‐Mañero, M., Bertomeu‐González, V., Castellano, J. M., Seijas‐Amigo, J., Núñez, J. E., Zuazola, P., González‐Juanatey, J. R., et al. (2020) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2020.09.021 · Cited by 29 · see citing works
- Authors
- 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.
- Affiliations
- Brigham and Women's Hospital (US)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2017-04-20
- Volume
- 376
- Issue
- 16
- Pages
- 1517-1526
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2596676407
- Cited by
- 369
- References
- 14
- Citations by year
- 2026: 18 · 2025: 32 · 2024: 25 · 2023: 31 · 2022: 33 · 2021: 27 · 2020: 46 · 2019: 50 · 2018: 56 · 2017: 51
- FWCI
- 56.82
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (publishedVersion, other-oa)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- bococizumab, PCSK9 inhibitors, antidrug antibodies, LDL cholesterol lowering, hyperlipidemia, statin therapy, apolipoprotein B, lipoprotein(a), cardiovascular events, injection site reactions, monoclonal antibody therapy, drug durability, treatment response heterogeneity, cardiovascular risk reduction
- MeSH terms
- Proprotein Convertase 9, PCSK9 Inhibitors, Antibodies, Anticholesteremic Agents, Female, Follow-Up Studies, Humans, Hypercholesterolemia, Injections, Subcutaneous, Lipids, Cholesterol, LDL, Male, Middle Aged, Treatment Outcome, Antibodies, Monoclonal, Humanized
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
