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PCSK9 Inhibitor Non-Response in a Patient with Preserved LDL Receptor

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PCSK9 Inhibitor Non-Response in a Patient with Preserved LDL Receptor PCSK9 inhibitor non-response in a patient with preserved LDL receptor function: A case study Losh C, Underberg J Murray Hill Medical Group and New York University School of Medicine, New York, NY Background Results Conclusions PCSK9 inhibitors (PCSK9Is) are monoclonal LDL-C levels after three and seven weeks Absence of LDL receptor activity is not the antibodies that bind to serum PCSK9 and Response to Statin Therapy of therapy with alirocumab 75 mg were 235 only mechanism of PCSK9 inhibitor non- delay LDL receptor degradation. Two mg/dL and 239 mg/dL respectively. Three response. An alteration in the PCSK9 PCSK9Is are commercially available: and seven weeks after up-titration, LDL-C Intervention LDL-C (mg/dL) Change (%) evolocumab and alirocumab. FDA approved binding site for alirocumab and indications include LDL cholesterol (LDL-C) was 249 mg/dL and 292 mg/dL, evolocumab is proposed as a hypothetical lowering on maximally tolerated statin respectively. Total duration of alirocumab None 283 — mechanism for non-response in this therapy was 16 weeks. LDL-C was 253 therapy in patients with ASCVD and Familial patient. Other alternatives include Hypercholesterolemia (FH). Among patients mg/dL after 3 weeks of therapy with pitavastatin 2 mg 238 -15.9% immunogenicity, noncompliance, or faulty with LDL receptor mutations, those with evolocumab, at which time PCSK9 1 dose/week partial loss of function typically respond well inhibitor therapy was discontinued due to pitavastatin 2 mg injection techniqueReferences. 216 -23.7% to PCSK9 inhibition, while those with lack of clinical response. 2 doses/week Amgen Inc. (2015). Repatha: Highlights of homozygous receptor-negative mutations, pitavastatin 2 mg ie. the null-null genotype, have minimal to no 195 -31.1% Prescribing Information. Retrieved from 5 doses/week response. http://pi.amgen.com/united_states/repatha/repa tha_pi_hcp_english.pdf Blom, D. J., Hala, T., Bolognese, M., Lillestol, M. Objective Non-Response to PCSK9I Therapy J., Toth, P. D., Burgess, L., …Stein, E. A. To describe PCSK9I non-response in a patient with preserved LDL receptor function. (2014). A 52-week placebo-controlled trial of Intervention evolocumab in hyperlipidemia. The New LDL-C (mg/dL) Change (%) Methods (duration) England Journal of Medicine, 370, 1809-19. Regeneron Pharmaceuticals Inc. (2015). Praluent: A 67 year old female with lifelong off-treatment LDL-C in the range of 250-280 mg/dL alirocumab 75 mg and statin intolerance presented to our clinic. The family history was limited by 235 -17.0% Highlights of Prescribing Information. Retrieved (3 weeks) from premature non-cardiac death of both parents. Two of her children have normal lipid alirocumab 75 mg http://www.regeneron.com/Praluent/Praluent- panels; the third was not evaluated. The physical exam was unremarkable. The initial 239 -15.5% (7 weeks) fpi.pdf off-treatment lipid panel showed a total cholesterol of 366 mg/dL and an LDL-C of 283 Robinson J. G., Farnier, M., Krempf, M., alirocumab 150 mg mg/dL, with normal triglycerides and HDL-C. Her LDL levels were strongly suggestive 249 -12.0% Bergeron, J., Luc, G., Averna, M., Stroes, E. S., of heterozygous FH, and she was treated accordingly. The patient was re-challenged (3 weeks) …Kastelein, J. J. P. (2015). Efficacy and safety alirocumab 150 mg of alirocumab in reducing lipids and with pitavastatin 2 mg. On maximally tolerated dose frequency of 5 times/week she 292 +3.2% experienced a LDL reduction of 31.1%, suggestive of preserved LDL receptor function. (7 weeks) cardiovascular events. The New England Journal of Medicine, 372, 1489-99. Subsequent adverse effects led to discontinuation of pitavastatin. Monotherapy with evolocumab 140 mg 253 -10.6% alirocumab was initiated at 75 mg subcutaneously every 2 weeks and up-titrated after 8 (3 weeks) weeks to 150 mg. Subsequently she was given a trial of evolocumab 140 mg. Injection technique training and direct observation of periodic injections were used to support compliance..
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