Drug Trough Levels And Primary Nonresponse To Antitnf Therapy In Moderate-Severe Crohn Disease. Results Of The Optimiza Study

Background and aim: Biological therapy is now the mainstay treatment for the patients with moderate/severe IBD. The efficacy of treatment is no longer measured only in the induction of clinical remission, endoscopic healing being considered more important since it's achievement can influence the long term outcome of the disease. The majority of clinical trials report endoscopic results after one year of maintenance treatment. The aim of our study was to observe the frequency of mucosal healing and its persistence in a group of IBD patients with clinical response to biological therapy during long term follow up (over 2 years). Methods: All patients with IBD that received biological treatment admitted in our department were prospectively followed. In all ileocolonoscopies were performed at 6 months intervals with description of all lesions encountered (periodic endoscopic or radiologic evaluations are part of the protocol issued by National Health Insurance House and are required for the approval of reimbursed biological treatment). Mucosal healing (MH) was defined as lack of ulcers, ulcerations or aftous erosions. The presence of erythema, edema, and inflammatory pseudopolyps did not preclude the diagnosis of MH. Demographic and clinical data were noted as well as the type, dose, and frequency of biological and associated (e.g. immunosuppressive) treatments. Only patients treated over 2 years were included in the analysis. Results: 52 patients (27 males, 25 females, mean age 36.9+/-12.2 years) received biological therapy (38 infliximab and 14 adalimumab) for a period longer than 24 months (24-72, mean 38.67 months), 43 with Crohn's disease (CD) and 9 with ulcerative colitis (UC). Mucosal healing was obtained in 80.77% patients. The mean time to MH was of 10.85 (6-36) months. 26.19% of patients needed more than one year to achieve MH. From patients with MH, 40.48% experienced recurrent endoscopic lesions and clinical flare during follow up. The only factor associated with long term MH (maintained during the observation period) was the presence of MH 6 months after initiation of maintenance treatment with biologics (p=0.022). The combined treatment with immunosupressors or the use of biological therapy at first flare of disease did not influence the occurrence or persistence of MH in our group of patients. Conclusions: In patients with clinical remission obtained with biological treatment long term endoscopic follow up shows that mucosal healing can be achieved in the majority of cases. A rapid endoscopic response (mucosal healing after the first 6 months of maintenance therapy) predicts sustained, long term, endoscopic remission.