HMO-4 Immunogenicity to second anti-TNF therapy (IMSAT): implications for sequencing of biologic therapy

IntroductionAnti-TNF treatment failure in patients with IBD is common. International guidelines recommend switching out of class when anti-TNF drug levels are therapeutic and within class with an immunomodulator when anti-TNF drug levels are suboptimal and associated with antibody development.We sought to define the: 1) risk of immunogenicity to a second anti-TNF stratified by immunogenicity to first anti-TNF, 2) rates of drug persistence following failure to first anti-TNF drug and 3) strategies to mitigate development of immunogenicity.MethodsWe performed a retrospective cohort study across 38 UK hospitals. 1058 patients [532 (51%) male, 755 (71%) Crohn’s disease] had both infliximab and adalimumab therapeutic drug monitoring performed by our service from May 2013 to October 2020 were identified. Drug and antibody levels were measured using the IDKmonitor® drug-tolerant ELISA assays. Treatment failure included primary nonresponse, secondary loss of response, adverse drug reactions and IBD-related surgery, and patients were identified by case note review. Immunogenic failure was defined as treatment failure with suboptimal drug levels (infliximab level