Abstract
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 <2 mg/L, adalimumab level <6 mg/L) with an antibody concentration ≥10 AU/ml. Pharmacodynamic (PD) failure was defined as treatment failure despite adequate drug levels.ResultsPatients who developed immunogenicity to adalimumab (first) were more likely to develop immunogenicity to infliximab (second) (64% vs 40%, p < 0.001), and patients who developed immunogenicity to infliximab (first) were more likely to develop immunogenicity to adalimumab (second) (34% vs 20%, p = 0.002). Patients who developed: antibodies and undetectable drug, low drug levels, or low drug levels with immunogenicity to infliximab (first), were more likely to develop these outcomes to adalimumab (second) (all p<0.001).There was no difference in drug persistence to second anti-TNF in patients with pharmacodynamic and immunogenic treatment failure to first anti-TNF (p = 0.86). In patients with immunogenic (but not pharmacodynamic) failure, commencing an immunomodulator at the time of switching to second anti-TNF drug was associated with longer drug persistence than in patients treated with an immunomodulator throughout or not all (Figure 1).Abastract HMO-4 Figure 1Drug persistence to second anti-TNF in patients stratified by immunomodulator useConclusionsImmunogenicity to the first anti-TNF was associated with immunogenicity to the second anti-TNF, irrespective of drug sequence. Commencing an immunomodulator at the time of switching to second anti-TNF was associated with improved drug persistence in immunogenic, but not pharmacodynamic, failure. However, 50% of patients remained on second anti-TNF at 5 years in both groups, suggesting switching in-class may be appropriate, irrespective of the cause of treatment failure to first anti-TNF.