P656 Are trough levels of anti-TNF drugs related with treatment failure and duration of treatment?

Abstract

Introduction: Therapeutic drug monitoring of infliximab (IFX) and adalimumab (ADA) in inflammatory bowel disease are commonly used if patients show loss of response, but there are scarce data about the influence of trough levels on prognosis. Aims & Methods: The aim of the study was to evaluate the relationship between drug concentration of anti-TNF and treatment failure and duration of treatment in a real life environment. METHODS A prospective observational study was performed in a cohort of patients with inflammatory bowel disease. Patients were included consecutively through visits to the hospital to receive IFX or ADA. Inclusion criteria were all age >18 year patients, being treated with one of the study drugs at standard dose as maintenance therapy and giving consent to participate in the study. In the first visit, blood samples were extracted for drug concentration determination. Patients were followed-up for the next 2 years. Trough drug concentrations and drug antibodies were measured by an ELISA technique (Promonitor). Patients with IFX levels <3 mcg/mL and ADA <5 mcg/mL were considered under lower limit of therapeutic range (LLTR). After the follow-up period, the number of patients that continued (success) or discontinued (failures) the treatment were analyzed. Any change in dosage (intensification) or in the type of drug was considered as discontinuation of the treatment. Chi square test was used to analyze the dependence between the categorical variables and t-student for continuous variables with normal distribution. Result(s): 134 patients were consecutively included, 53 male (40%), 92 (68%) patients with Crohn's disease (CD) and 42 (32%) with ulcerative colitis (UC), 82 (61%) received maintenance treatment with IFX and 52 (39%) with ADA. Mean age was 43 [19-71] years. After finishing the follow-up, 107 (79%) patients continued the same treatment regimen (success). A total of 59% of this group of patients were with drug concentrations above LLTR. The remaining 27 patients changed their treatment (failures). In the failure group, only 41% of the patients were above LLTR, 18.2% less with respect to success treatment group. These results did not reach statistical significance (p=0.09), but are in agreement with current evidence. When type of inflammatory disease was analyzed, a greater percentage of patients below the LLTR were found in the UC group (41.3% vs 52.4%, CD and UC respectively), but the difference did not reach statistical significance. Regarding the duration of the treatments, the duration was similar in the group of patients with low concentrations compared to the group with high drug concentrations (46.6 vs 42.6 months). However, when the duration of treatment was analyzed in patients who discontinued, significant differences were observed (43.8 vs 20.2 months in the LLTR groups respectively). Therefore, there are patients who relapse rapidly even with drug levels above LLTR. We observed 14 patients with positive antibodies, all of them with drug concentrations below the LLTR. Conclusion(s): The percentage of patients who continue treatment was higher when drug concentrations were above LLTR. However, these high levels did not prevent the early relapse of some of them.