title: Evaluation of immunogenicity of LY2963016 insulin glargine compared with Lantus® insulin glargine in patients with type 1 or type 2 diabetes mellitus.
abstract: OBJECTIVE
  To compare the immunogenicity profiles and the potential effects on clinical outcomes of LY2963016 insulin glargine (LY IGlar) and Lantus® insulin glargine (IGlar), products with identical primary amino acid sequences, in patients with type 1 or type 2 diabetes mellitus (T1DM or T2DM).
  
  
  METHODS
  To assess immunogenicity, anti-insulin glargine antibodies (measured as percent binding) were compared between treatments in 52-week (open-label) and 24-week (double-blind) randomized studies in total study populations of patients with T1DM (N = 535) and T2DM (N = 756), respectively, and two subgroups of patients with T2DM: insulin-naïve patients and those reporting prestudy IGlar treatment (prior IGlar). Relationships between insulin antibody levels and clinical outcomes were assessed using analysis of covariance and partial correlations. Insulin antibody levels were assessed using Wilcoxon rank sum. Treatment comparisons for treatment-emergent antibody response (TEAR) and incidence of detectable antibodies were analysed using Fisher's exact test.
  
  
  RESULTS
  No significant treatment differences were observed for insulin antibody levels, incidence of detectable anti-insulin glargine antibodies, or incidence of TEAR [overall and endpoint, by last-observation-carried-forward (LOCF)] in patients with T1DM or patients with T2DM, including the insulin-naïve subgroup. A statistically significant difference was noted in the overall incidence of detectable antibodies but not at endpoint (LOCF) nor in TEAR for the prior IGlar subgroup of patients with T2DM. Insulin antibody levels were low (<5%) in both treatment groups. Insulin antibody levels or developing TEAR was not associated with clinical outcomes.
  
  
  CONCLUSIONS
  LY IGlar and IGlar have similar immunogenicity profiles; anti-insulin glargine antibody levels were low for both treatments, with no observed effect on efficacy and safety outcomes.
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: L L
authors.initials: LL
authors.lastname: Ilag
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Deeg
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: T
authors.initials: T
authors.lastname: Costigan
authors.affiliation: Baylor Endocrine Center, Dallas, TX, USA.
authors.forename: P
authors.initials: P
authors.lastname: Hollander
authors.affiliation: Texas Diabetes and Endocrinology, Austin, TX, USA.
authors.forename: T C
authors.initials: TC
authors.lastname: Blevins
authors.affiliation: University of California, San Diego, San Diego, CA, USA.
authors.forename: S V
authors.initials: SV
authors.lastname: Edelman
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Konrad
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Ortmann
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: R K
authors.initials: RK
authors.lastname: Pollom
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: W J
authors.initials: WJ
authors.lastname: Huster
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: J S
authors.initials: JS
authors.lastname: Zielonka
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Prince
mesh_terms: D058070:Asymptomatic Diseases / Q000453:epidemiology; D059451:Biosimilar Pharmaceuticals / Q000009:adverse effects / Q000627:therapeutic use; D003429:Cross Reactions; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D004311:Double-Blind Method; D004342:Drug Hypersensitivity / Q000150:complications / Q000453:epidemiology / Q000209:etiology* / Q000276:immunology; D006801:Humans; D006943:Hyperglycemia / Q000517:prevention & control; D007003:Hypoglycemia / Q000139:chemically induced / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D055261:Immunogenetic Phenomena / Q000187:drug effects; D015994:Incidence; D007330:Insulin Antibodies / Q000032:analysis*; D000069036:Insulin Glargine / Q000009:adverse effects* / Q000031:analogs & derivatives* / Q000627:therapeutic use; D061386:Insulin, Regular, Human / Q000009:adverse effects / Q000031:analogs & derivatives / Q000235:genetics / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D059451:Biosimilar Pharmaceuticals; D007004:Hypoglycemic Agents; D007330:Insulin Antibodies; D061386:Insulin, Regular, Human; C000606659:LY2963016 insulin glargine; D011994:Recombinant Proteins; D000069036:Insulin Glargine
keywords: LY2963016 insulin glargine; biosimilar insulin; insulin antibody; insulin glargine