P436 Secondary loss of response to anti-TNF in inflammatory bowel diseases. Therapeutic drug monitoring. Utility in clinical practice

Abstract

Background: Secondary loss of response (LOR) occurs in 23-46% when determined acording to dose intensification. Intensification of treatment is effective in about 60-90% of the cases and switching to non antiTNF drugs in 19-68%. Immunogenicity is not the only fac-tor affecting anti-TNF drug clearance and efficacy. The assessment of disease activity by measuring the seric levels of anti-TNF drug levels facilitates rational decisions on management of LOR. Method(s): Restrospective study in our institution in patients with ulcerative colitis (UC) or Crohn's disease (CD) with LOR and thera-peutic drug monitoring from february 2015 to september 2016.The measurement of anti-TNF drug levels and anti-drugs antibodies (ADAS) levels was performed with ELISA assays drug concentration. The cut-off for drug levels in therapeutic range was 3-5 ug/mL for infliximab and 5-8 ug/mL for adalimumab. Result(s): A total of 42 patients were included, 32 with CD (76%) with Harvey-Bradshaw Index (HBI) >4 points and 10 patients with UC with Partial Mayo Score (PMS) >2 points with increase in C-reactive protein (PCR) or fecal calprotectin. 18 patients underwent in treatment with infliximab and 24 with adalimumab. The average time of evolution of disease was 12.6+/-8.77 years. The average time under biological treatment was 55.92+/-30.6 months. 38% had previously received another biological drug, 52% had previous intensifications and 58% received concomitant immunomodulators. 24% of patients presented levels in therapeutic range, 40% had low drug levels and absence of anti drugs antibodies (ADAS-), 10% had unde-tectable drug levels and positive anti drug antibodies (ADAS+), 26% of patients had high drugs level. The therapeutic strategy chosen for each group was: 15% of patients no change in treatment, 44% increase antiTNF dose or decrease infusion interval (intensification), 10% switch to another antiTNF drug, 24% switch to non anti-TNF. The clinical response (decrease of the PMS for UC >=3 points and de-crease of HBI >=3 points for CD) was reached in 42.8% of patients and remission (PMS 8 and a PMS >8 allowed to identify low drug levels with accuracy AUC = 0.689 and 0.88 (p<0.0001) respectively. Conclusion(s): Patients with LOR frequently had low drug levels and negative anti-drug antibodies. Intensification treatment sought to be effective despite the high number of patients who previously needed an increase in the dose of their anti-TNF treatment. 26% of patients needed to switch to non anti-TNF and, in these patients, monitoring anti-TNF, drug levels might allow to change the drug prescribed in order to avoid non-effective treatments.