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Anti‐TNF‐alpha Antibodies : Pharmacological Properties and Clinical Aspect in Autoimmune Diseases
Author(s) -
Cetrone Michela,
Tricarico Domenico
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1202.2
Subject(s) - adalimumab , infliximab , medicine , golimumab , etanercept , antibody dependent cell mediated cytotoxicity , drug , pharmacology , certolizumab pegol , pharmacodynamics , biosimilar , immunogenicity , immunology , antibody , monoclonal antibody , tumor necrosis factor alpha , pharmacokinetics
Therapeutic IgG1 mAbs have high efficacy in treating TNFα‐related immunological diseases, however differing in their pharmacological and clinical responses. Several mAbs are currently available: Infliximab, Etanercept, Adalimumab, Certolizumab, Golimumab, and the biosimilars of Infliximab. These mAbs show a neutralizing action against TNF‐α, which is mediated by the FAB fragment, and complement‐dependent cytotoxicity (CDC) and antibody‐mediated cellular cytotoxicity (ADCC) which are mediated by the Fc fragment. However, the current therapy in these disorders does not fulfill the clinical requests in some patients and the factors affecting the lack of response are not fully understood. Possible explanations for therapeutic failure include insufficient compliance/bioavailability, pharmacokinetics (PK) and pharmacodynamic (PD) issues and the induction of anti‐drug‐antibodies (ADA). Two main strategies available in case of non response are: (1) increasing drug exposure by shortening the dosing interval or increasing the dose and (2) switching to another drug. More recently, the use of therapeutic strategies based on the measurements of the anti‐TNF drug levels and ADA, rather than dose‐escalation has proven to be cost‐effective, as this allows individualized patient‐tailored strategies. In the present review we have analyzed the state of the art and possible perspectives in the TNF‐α related autoimmune diseases taking into account the pharmaco‐economic impact of the novel strategy and of the biosimilar drugs.