Taltz ® (ixekizumab) injektion

För fullständig produktresumé för Taltz® se FASS.

Denna information är endast avsedd för sjukvårdspersonal verksam i Sverige och som svar på din fråga. Informationen nedan är på engelska

Taltz® (ixekizumab): humana kontra humaniserade monoklonala antikroppar

Aktuella bevis tyder på att beteckningen för en monoklonal antikropp som human eller humaniserad inte har någon inverkan på total effekt och säkerhetsprofil.

Differences Between Human and Humanized Monoclonal Antibodies

Ixekizumab is a humanized IgG4 mAb that selectively binds with high affinity (<3pM) and specificity to IL-17A, a proinflammatory cytokine.1,2

The nomenclature assigned to an mAb (ie, human or humanized) is dependent on the variable region of the immunoglobulin. This site confers binding specificity and affinity of a therapeutic antibody.3

Although there are a number of differences between human and humanized mAbs, current evidence indicates that this distinction is not associated with a measurable impact on overall efficacy and safety profiles of a therapeutic antibody.3 This is reflected in the updated mAb nomenclature recommended by the International Nonproprietary Names Expert Group.4

Clinicians should individually assess each mAb for its clinical impact, in particular safety and efficacy.3

Human Monoclonal Antibodies

Generation of fully human mAbs can

  • start with either phage display technology or animal immunizations

  • be developed in transgenic mice that have been genetically engineered with the human Ig locus, and

  • have mutations which have been introduced by the mouse somatic mutation machinery.3,5

Humanized Monoclonal Antibodies

Generation of humanized mAbs

  • starts with animal immunizations, typically utilizing mice

  • involves developing initially in wild-type mice with a native genome bearing the mouse Ig locus

  • involved grafting the mouse-derived variable region onto a human antibody sequence utilizing molecular engineering technology to create the humanized mAb

  • can result in mAbs that, in total, have high human amino acid sequence homology with differences limited to complementarity determining regions within the variable region of the antibody, and

  • can be specifically engineered to have fully human frameworks with no mutations from germline in these areas.3

Impact on Safety or Efficacy

Changes in the amino acid sequence homology to human amino acid sequences of either fully human or humanized mAbs can contribute to the development of ADAs, thereby potentially limiting clinical efficacy.3,6

The distinction between fully human and humanized mAbs has no predictable impact on the development of ADAs. Rather, a number of intrinsic and extrinsic factors, including but not limited to the amino acid sequence of an mAb, are involved in the development of ADAs for a given therapeutic mAb.3

Approximately 9–17% of adult plaque psoriasis patients treated with ixekizumab at the recommended dosing regimen developed anti-drug antibodies, the majority of which were low titres and not associated with reduced clinical response up to 60 weeks of treatment.2

  • However, approximately 1% of patients treated with ixekizumab had confirmed neutralising antibodies associated with low drug concentrations and reduced clinical response.2

In paediatric psoriasis patients treated with ixekizumab at the recommended dosing regimen up to 12 weeks, 21 patients (18%) developed anti-drug antibodies, approximately half were low titer and 5 patients (4%) had confirmed neutralizing antibodies associated with low drug concentrations.2

  • There was no association with clinical response or adverse events.2

In psoriatic arthritis patients treated with ixekizumab at the recommended dosing regimen up to 52 weeks, approximately 11% developed anti-drug antibodies, the majority of which were low titre, and approximately 8% had confirmed neutralising antibodies.2

  • No apparent association between the presence of neutralising antibodies and impact on drug concentration or efficacy was observed. 2

In radiographic axial spondyloarthritis patients treated with ixekizumab at the recommended dosing regimen up to 16 weeks, 5.2% developed anti-drug antibodies, the majority of which were low titer, and 1.5% (3 patients) had neutralising antibodies (NAb). In these 3 patients, NAb-positive samples had low ixekizumab concentrations and none of these patients achieved an ASAS40 response.2

In non‑radiographic axial spondyloarthritis patients treated with ixekizumab at the recommended dosing regimen for up to 52 weeks, 8.9% developed anti-drug antibodies, all of which were low titer; no patient had neutralising antibodies; and no apparent association between the presence of anti‑drug antibodies and drug concentration, efficacy, or safety was observed.2

Across all indications, an association between immunogenicity and treatment emergent adverse events has not been clearly established.2

References

1. Data on file, Eli Lilly and Company and/or one of its subsidiaries.

2. Taltz [summary of product characteristics]. Eli Lilly Nederland B.V., The Netherlands.

3. Mallbris L, Davies J, Glasebrook A, et al. Molecular insights into fully human and humanized monoclonal antibodies: what are the differences and should dermatologists care? J Clin Aesthet Dermatol. 2016;9(7):13-15. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5022998/

4. World Health Organization. Revised monoclonal antibody (mAb) nomenclature scheme. https://www.who.int/medicines/services/inn/Revised_mAb_nomenclature_scheme.pdf?uaD1. Published May 26, 2017. Accessed January 5, 2021.

5. Di Noia JM, Neuberger MS. Molecular mechanisms of antibody somatic hypermutation. Annu Rev Biochem. 2007;76:1-22. http://dx.doi.org/10.1146/annurev.biochem.76.061705.090740

6. Jullien D, Prinz JC, Nestle FO. Immunogenicity of biotherapy used in psoriasis: the science behind the scenes. J Invest Dermatol. 2015;135(1):31-38. http://dx.doi.org/10.1038/jid.2014.295

Glossary

ADA = anti-drug antibody

Ig = immunoglobulin

IgG4 = immunoglobulin G subclass 4

IL-17A = interleukin-17A

mAb(s) = monoclonal antibody

Datum fӧr senaste ӧversyn 2021 M01 05


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