P436 Secondary loss of response to anti-TNF in inflammatory bowel diseases. Therapeutic drug monitoring. Utility in clinical practice
Jimenez M.*1, Sierra-Ausin M.1, Cano N.1, Suarez P.1, Fernandez-Gundin M.1, Saez-Villafañe M.2, Monteserin L.1, Molina G.1, Reyes N.1, Viso D.1, Jorquera F.1
1Hospital Universitario de Leόn, Gastroenterology, Leόn, Spain 2Hospital Universitario de Leόn, Pharmacoloy, Leόn, Spain
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.
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.
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.
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.