Evolocumab side effects
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Evolocumab Side Effects: A Comprehensive Review
Introduction to Evolocumab and Its Use
Evolocumab is a fully human monoclonal antibody that targets proprotein convertase subtilisin/kexin type 9 (PCSK9), significantly reducing low-density lipoprotein cholesterol (LDL-C) levels. It is primarily used in patients with hypercholesterolemia, particularly those who are statin-intolerant or have familial hypercholesterolemia .
General Safety and Tolerability
Overall Adverse Events (AEs)
In a pooled safety analysis involving over 6000 patients from phase 2 and 3 trials, the overall rates of adverse events (AEs) were similar between the evolocumab and control groups. Specifically, 51.1% of patients on evolocumab experienced AEs compared to 49.6% in the control group during the parent trials, and 70.0% versus 66.0% during the first year of open-label extension (OLE) trials.
Serious Adverse Events (SAEs)
The incidence of serious adverse events (SAEs) was also comparable between the evolocumab and control groups in both the parent and OLE trials. This suggests that evolocumab does not significantly increase the risk of serious health issues compared to standard treatments.
Specific Side Effects
Muscle-Related Adverse Events
Muscle-related side effects are a common concern with cholesterol-lowering therapies. In the GAUSS-2 trial, muscle-related AEs were reported in 12% of evolocumab-treated patients, which was lower than the 23% reported in the ezetimibe-treated group. This indicates a favorable muscle safety profile for evolocumab.
Neurocognitive Adverse Events
Neurocognitive AEs were infrequent but slightly more common in the evolocumab group. In the parent studies, neurocognitive events were reported in 0.1% of evolocumab patients compared to 0.3% in the control group. However, in the OLE trials, 0.9% of evolocumab patients reported neurocognitive AEs compared to 0.3% in the control group .
Laboratory Abnormalities
Elevations in serum transaminases, bilirubin, and creatine kinase were infrequent and similar between the evolocumab and control groups. This suggests that evolocumab does not significantly impact liver or muscle enzyme levels.
Vitamin E and Steroid Hormone Levels
A study examining the effects of evolocumab on vitamin E and steroid hormone levels found that while absolute vitamin E levels decreased by 16%, they increased by 19% when normalized for cholesterol. There were no significant changes in cortisol, adrenocorticotropic hormone, or gonadal hormones, indicating no adverse effects on these parameters.
Long-Term Safety
Cardiovascular Events
Long-term studies, including the OSLER-1 trial, demonstrated that evolocumab significantly reduced LDL-C levels and the incidence of cardiovascular events over a median follow-up of 11.1 months. The rate of cardiovascular events was reduced from 2.18% in the standard-therapy group to 0.95% in the evolocumab group .
Diabetes and Glycaemia
In the FOURIER trial, evolocumab did not increase the risk of new-onset diabetes or worsen glycaemia in patients with or without diabetes at baseline. The incidence of adverse events was similar between the evolocumab and placebo groups, regardless of diabetes status.
Conclusion
Evolocumab is generally well-tolerated with a safety profile comparable to standard cholesterol-lowering therapies. While some specific side effects such as neurocognitive events and muscle-related AEs have been reported, their incidence is relatively low. Long-term studies support the safety and efficacy of evolocumab in reducing cardiovascular events without significantly increasing the risk of serious adverse events or new-onset diabetes. Overall, evolocumab presents a favorable benefit-risk profile for patients requiring significant LDL-C reduction.
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