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Would your patient benefit from a monoclonal antibody?

The Journal of Family Practice. 2022 October;71(8):E1-E8 | doi: 10.12788/jfp.0481
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These unique agents may be the answer when other treatments fail or are intolerable for patients with asthma, atopic dermatitis, hyperlipidemia, osteoporosis, or migraine headaches.

PRACTICE RECOMMENDATIONS

› Consider anti-immunoglobulin E, anti-interleukin 5, or anti-interleukin 4/interleukin 13 for patients with moderate-to-severe asthma and type 2 airway inflammation. B

› Consider dupilumab for patients with moderate-to-severe atopic dermatitis (with or without topical corticosteroids), or when traditional oral therapies are inadequate or contraindicated. B

› Consider proprotein convertase subtilisin/kexin type 9 inhibitors for patients with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease when maximally tolerated statins or ezetimibe have not lowered low-density lipoprotein cholesterol levels far enough. A

Strength of recommendation (SOR)

A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series

Hyperlipidemia

Three MAbs are approved for use in hyperlipidemia: the angiopoietin-like protein 3 ­(ANGPTL3) inhibitor evinacumab (Evkeeza)24 and 2 proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, evolocumab (Repatha)25 and alirocumab (Praluent).26

ANGPTL3 inhibitors block ­ANGPTL3 and reduce endothelial lipase and lipoprotein lipase activity, which in turn decreases low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol ­(HDL-C), and triglyceride formation. PCSK9 inhibitors prevent PCSK9 from binding to LDL receptors, thereby maintaining the number of active LDL receptors and increasing LDL-C removal.

Evinacumab is indicated for homozygous familial hypercholesterolemia and is administered intravenously every 4 weeks. Evinacumab has not been evaluated for effects on cardiovascular morbidity and mortality.

Evolocumab 140 mg SC every 2 weeks or 420 mg SC monthly has been studied in patients on statin therapy with LDL-C ≥ 70 mg/dL. Patients on evolocumab experienced significantly less of the composite endpoint of cardiovascular death, myocardial infarction (MI), stroke, hospitalization for unstable angina, or coronary revascularization compared with placebo (9.8% vs 11.3%; hazard ratio [HR] = 0.85; 95% CI, 0.79-0.92; NNT = 67.27

Alirocumab 75 mg SC every 2 weeks has also been studied in patients receiving statin therapy with LDL-C ≥ 70 mg/dL. Patients taking alirocumab experienced significantly less of the composite endpoint of death from coronary heart disease, nonfatal MI, ischemic stroke, or hospitalization for unstable angina compared with placebo (9.5% vs 11.1%; HR = 0.85; 95% CI, 0.78-0.93; NNT = 63).28

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