title: Effect of mipomersen on LDL-cholesterol in patients with severe LDL-hypercholesterolaemia and atherosclerosis treated by lipoprotein apheresis (The MICA-Study).
abstract: In this study, we evaluated the effect of mipomersen in patients with severe LDL-hypercholesterolaemia and atherosclerosis, treated by lipid lowering drugs and regular lipoprotein apheresis.
  
  
  
  This prospective, randomized, controlled phase II single center trial enrolled 15 patients (9 males, 6 females; 59 ± 9 y, BMI 27 ± 4 kg/m2) with established atherosclerosis, LDL-cholesterol ≥130 mg/dL (3.4 mmol/L) despite maximal possible drug therapy, and fulfilling German criteria for regular lipoprotein apheresis. All patients were on stable lipid lowering drug therapy and regular apheresis for >3 months. Patients randomized to treatment (n = 11) self-injected mipomersen 200 mg sc weekly, at day 4 after apheresis, for 26 weeks. Patients randomized to control (n = 4) continued apheresis without injection. The primary endpoint was the change in pre-apheresis LDL-cholesterol.
  
  
  
  Of the patients randomized to mipomersen, 3 discontinued the drug early (<12 weeks therapy) for side effects. For these, another 3 were recruited and randomized. Further, 4 patients discontinued mipomersen between 12 and 26 weeks for side effects (moderate to severe injection site reactions n = 3 and elevated liver enzymes n = 1). In those treated for >12 weeks, mipomersen reduced pre-apheresis LDL-cholesterol significantly by 22.6 ± 17.0%, from a baseline of 4.8 ± 1.2 mmol/L to 3.7 ± 0.9 mmol/L, while there was no significant change in the control group (+1.6 ± 9.3%), with the difference between the groups being significant (p=0.006). Mipomersen also decreased pre-apheresis lipoprotein(a) (Lp(a)) concentration from a median baseline of 40.2mg/dL (32.5,71) by 15% (-19.4,3.6) though without significance (p=0.3).
  
  
  
  Mipomersen reduces LDL-cholesterol (significantly) and Lp(a) (non-significantly) in patients on maximal lipid-lowering drug therapy and regular apheresis, but is often associated with side effects.
authors.affiliation: Medizinische Klinik II, LMU, Klinikum der Universität München, Campus Großhadern, Germany. Electronic address: elisa.waldmann@med.uni-muenchen.de.
authors.forename: Elisa
authors.initials: E
authors.lastname: Waldmann
authors.affiliation: Medizinische Klinik IV, LMU, Klinikum der Universität München, Campus Innenstadt, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Vogt
authors.affiliation: Department of Medical Informatics, Biometry, and Epidemiology, Ludwig Maximilians University Munich, Munich, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Crispin
authors.affiliation: Medizinische Klinik II, LMU, Klinikum der Universität München, Campus Großhadern, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Altenhofer
authors.affiliation: Medizinische Klinik II, LMU, Klinikum der Universität München, Campus Großhadern, Germany.
authors.forename: Ina
authors.initials: I
authors.lastname: Riks
authors.affiliation: Medizinische Klinik II, LMU, Klinikum der Universität München, Campus Großhadern, Germany.
authors.forename: Klaus G
authors.initials: KG
authors.lastname: Parhofer
mesh_terms: D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D053299:Apolipoprotein B-100 / Q000235:genetics; D050197:Atherosclerosis / Q000097:blood / Q000175:diagnosis / Q000235:genetics / Q000628:therapy*; D015415:Biomarkers / Q000097:blood; D001781:Blood Component Removal / Q000379:methods*; D008078:Cholesterol, LDL / Q000097:blood*; D003131:Combined Modality Therapy; D005260:Female; D005858:Germany; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000175:diagnosis / Q000235:genetics / Q000628:therapy*; D017270:Lipoprotein(a) / Q000097:blood; D008297:Male; D008875:Middle Aged; D009841:Oligonucleotides / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: C569471:APOB protein, human; D000924:Anticholesteremic Agents; D053299:Apolipoprotein B-100; D015415:Biomarkers; D008078:Cholesterol, LDL; D017270:Lipoprotein(a); D009841:Oligonucleotides; C524142:mipomersen
keywords: Antisense oligonucleotide; Apolipoprotein B; Familial hypercholesterolaemia; Lipoprotein