title: Immunogenicity of infliximab and adalimumab: what is its role in hypersensitivity and modulation of therapeutic efficacy and safety?
abstract: BACKGROUND
  TNF-α inhibitors have demonstrated efficacy both as monotherapy and in combination with disease-modifying antirheumatic drugs (DMARDs) in the treatment of chronic inflammatory immune-mediated diseases such as rheumatoid arthritis, Crohn's disease, ankylosing spondylitis, psoriasis and/or psoriatic arthritis, and may be administered off-label to treat disseminated granuloma annulare systemic lupus erythematosus and systemic sclerosis. There are several TNF-α inhibitors available for clinical use including infliximab, adalimumab, golimumab, certolizumab pegol and etanercept.
  
  
  METHODS
  infliximab and adalimumab can induce the development of anti-infliximab (anti-IFX) and anti-adalimumab (anti-ADA) monoclonal antibodies (mAbs). In this review, we discuss the impact of anti-IFX and anti-ADA mAbs upon efficacy and safety of these biological agents.
  
  
  CONCLUSIONS
  IgG/IgE neutralizing antibodies against infliximab and adalimumab decrease the possibility of achieving a minimal disease activity state or clinical remission, decrease drug survival, increase the need for doctors to prescribe a higher drug dosage and, finally, favor the occurrence of adverse events. Concomitant administration of DMARDs such as methotrexate or leflunomide prevents the development of neutralizing Abs against infliximab and adalimumab.
authors.affiliation: a Department of Internal Medicine, Clinical immunology Unit , University of Genova , Viale Benedetto XV, n. 6, 16132 , Genova , Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Murdaca
authors.affiliation: a Department of Internal Medicine, Clinical immunology Unit , University of Genova , Viale Benedetto XV, n. 6, 16132 , Genova , Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Spanò
authors.affiliation: a Department of Internal Medicine, Clinical immunology Unit , University of Genova , Viale Benedetto XV, n. 6, 16132 , Genova , Italy.
authors.forename: Miriam
authors.initials: M
authors.lastname: Contatore
authors.affiliation: a Department of Internal Medicine, Clinical immunology Unit , University of Genova , Viale Benedetto XV, n. 6, 16132 , Genova , Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Guastalla
authors.affiliation: a Department of Internal Medicine, Clinical immunology Unit , University of Genova , Viale Benedetto XV, n. 6, 16132 , Genova , Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Penza
authors.affiliation: a Department of Internal Medicine, Clinical immunology Unit , University of Genova , Viale Benedetto XV, n. 6, 16132 , Genova , Italy.
authors.forename: Ottavia
authors.initials: O
authors.lastname: Magnani
authors.affiliation: a Department of Internal Medicine, Clinical immunology Unit , University of Genova , Viale Benedetto XV, n. 6, 16132 , Genova , Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Puppo
mesh_terms: D000068879:Adalimumab / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007154:Immune System Diseases / Q000188:drug therapy / Q000276:immunology; D007073:Immunoglobulin E / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D000069285:Infliximab / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D018124:Receptors, Tumor Necrosis Factor / Q000037:antagonists & inhibitors
chemical_list: D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D007073:Immunoglobulin E; D000069285:Infliximab; D000068879:Adalimumab
keywords: adalimumab; hypersensitivity reactions; immune-mediated diseases; immunogenicity; infliximab