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SP0082 Immunogenicity of biologics in inflammatory bowel diseases
  1. A Gils
  1. Dept of Pharmaceutical Sciences, KU Leuven, Leuven, Belgium


Anti-tumor necrosis factor-alpha and anti-integrin monoclonal antibodies show great benefits for inducing and maintaining remission, healing the mucosa and restoring the quality of life of patients with inflammatory bowel diseases. The therapeutic potential of these intrinsically powerful biologicals is tempered by a high variability in clinical response. Whereas primary non-response is defined as the lack of clinical response to treatment, assessed 8–12 weeks after initiation, secondary loss of response is defined as loss of clinical benefit after initially responding which can be attributed to disease-related or drug-related factors. Assays have been developed to determine the concentration of the therapeutic antibody in serum of the treated patient. The trough concentration is the concentration just before the next administration and for practical reasons therapeutic drug monitoring is mainly based on measurement of these trough concentrations. Several studies have reported correlations between through concentration of infliximab, adalimumab, golimumab, vedolizumab and clinical outcome. Optimal therapeutic windows have been defined for both infliximab and adalimumab. A panel of prospective studies in which dosage regimens are adapted in order to achieve target trough infliximab concentrations that correlate with beneficial therapeutic outcomes have been initiated.

Immunogenicity is the capability of biologicals to elicit an unwanted immune response that results in the formation of anti-drug antibodies. Anti-drug antibodies can be non-neutralizing or neutralizing. Non-neutralizing antibodies do not impair the drug-target interaction but may increase clearance of the drug resulting in lower serum concentrations. Neutralizing anti-drug antibodies compete with the target for the antigen-binding site and modulate directly the activity of the drug in addition to the enhanced clearance of the drug. A number of anti-drug antibody assays to quantify the immunogenicity of biologicals have been developed. Most of the assays quantify the total amount of anti-drug antibodies but comparing anti-drug antibody concentrations between different assays is hampered by the use of different calibrators and by the fact that drug tolerance differs among assays ranging from extreme drug sensitive over various forms of drug tolerant to drug resistant anti-drug antibody asssays. The clinical relevance of the different type of anti-drug antibody assays remains to be proven.

Combining therapeutic drug concentrations and anti-drug antibody concentrations with relevant patient, disease and drug information will lead to optimal dosing of patients aiming at optimal clinical, biochemical and endoscopic outcomes.

Disclosure of Interest A. Gils Grant/research support from: IIR grants from pfizer, Speakers bureau: speakers fee by Pfizer, MSD, Abbvie, Takeda, JnJ

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