• Antibody targeted therapy
• immunogenetics
• TNF

If you adhere to Homer's account of what happened in Troy, the greatest of all warriors, Achilles, would have been invincible if it hadn't been for the soft spot on his heel. So be it for all therapeutic antibodies, undoubtedly a successful innovation of modern-day pharmacotherapy and biotechnology. All engineered proteins, even recombinant human proteins such as γ-interferon or erythropoietin, are foreign to the human immune system and can induce antidrug antibodies, a phenomenon commonly known as immunogenicity.1–3 Antidrug antibodies are particularly important when they neutralise the drug or induce side effects such as infusion reactions. The antitumour necrosis factor (TNF) agents used to treat inflammatory bowel disease (IBD) are all engineered monocolonal antibodies or antibody fragments, and they are typically used in scheduled maintenance treatment. Therefore, a durable response over time is paramount and, as physicians caring for patients with Crohn's disease and ulcerative colitis, we have learnt to deal with immunogenicity and with the loss of response to anti-TNF treatment. However, burning questions on the nature and the relevance of antidrug antibodies remain unanswered >10 years after the introduction of these agents into the care of patients with IBD. Many open questions pertaining to the immunogenicity of monoclonal antibodies are generated by corporate proprietary interests of the pharmaceutical companies who have engineered these compounds. During the subsequent phases of clinical development antidrug antibodies are measured with in-house, not publically available, assays. Also for commercially available compounds, standardisation of trough level or antidrug antibody assays has not yet been achieved. Cohort studies released within years after the introduction of infliximab (IFX) into clinical practice have shown that anti-IFX antibodies (ATIs) are found in the majority of patients with IBD when this drug is used episodically.4 5 Scheduled maintenance use6 7 concomitant immunosuppressives4 6 7 and premedication …