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

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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 factor 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.

Methods: Restrospective study in our institution in patients with ulcerative colitis (UC) or Crohn's disease (CD) with LOR and therapeutic 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.

Results: 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 undetectable 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 decrease of HBI ≥3 points for CD) was reached in 42.8% of patients and remission (PMS≤2 for CU and HBI ≤4 for CD) in 57% at the end of follow-up. The baseline CRP was associated with a baseline mean CRP of 4.12±4.98 mg/L (p=0.018). A HBI >8 and a PMS >8 allowed to identify low drug levels with accuracy AUC = 0.689 and 0.88 (p<0.0001) respectively.

Conclusions: 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.

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