Current Practice for Therapeutic Drug Monitoring of Biopharmaceuticals in Inflammatory Bowel Disease.

Since the late 90s, biopharmaceuticals targeting tumor necrosis factor alpha have revolutionized the treatment of moderately to severely active inflammatory bowel disease. The robust efficacy witnessed in many patients stands in stark contrast with the observation of a proportion of patients who fail to respond or who lose response over time. Therapeutic drug monitoring has been proposed as a means to understand and respond to the variability in clinical response and remission. Various treatment algorithms have been proposed, but optimal use of these measurements in daily practice awaits additional prospective validation trials. This review provides an updated overview on the subject of therapeutic drug monitoring of biopharmaceuticals for the management of inflammatory bowel disease and how we could implement its concepts in a changing landscape.

Effectiveness of adalimumab in perianal fistulas in crohn's disease patients naive to anti-TNF therapy.

BACKGROUND: Data regarding the effectiveness of adalimumab (ADA) in the treatment of perianal fistula in patients with Crohn's disease (CD) naive to antitumor necrosis factor (TNF) therapy are scarce. AIM: : To assess the effectiveness of ADA in the treatment of perianal fistulas in CD patients naive to anti-TNF therapy. METHODS: A retrospective multicenter study was designed. The Fistula Drainage Assessment Index was used to assess the clinical response, and the Van Assche and Ng indexes to classify radiologic response (magnetic resonance imaging). RESULTS: A total of 46 patients (83% women, 83% complex fistula) were included. At 6 months, 72% of patients responded to ADA (54% remission, 18% partial response) and at 12 months 49% responded (41% remission, 8% partial response). Among patients with complex fistula, the response rate was 66% at 6 months and 39% at 12 months. Nine patients escalated the ADA dose to 40 mg weekly, 6 for partial response and 3 for absence of response. Thirty-three percent of these patients achieved remission after dose escalation. There was a good correlation between clinical and radiologic assessment of response (κ=0.68). In the multivariate analysis, complex fistula was the only predictor of a worse response (hazard ratio 0.083; 95% confidence interval, 0.0009-0.764; P=0.028). Adverse effects were recorded in 11% of patients. CONCLUSIONS: ADA was effective for the treatment of perianal fistulas in CD patients naive to anti-TNF drugs. We found a good correlation between clinical and radiologic assessment of therapy response.

Infliximab Dose Escalation as an Effective Strategy for Managing Secondary Loss of Response in Ulcerative Colitis.

BACKGROUND: The outcomes of infliximab dose escalation in ulcerative colitis (UC) have not been well evaluated. AIMS: To assess the short- and long-term outcomes of infliximab dose escalation in a cohort of patients with UC. METHODS: This was a multicenter, retrospective, cohort study. All consecutive UC patients who had lost response to infliximab maintenance infusions and who underwent infliximab dose escalation were included. Post-escalation short-term clinical response and remission were evaluated. In the long term, the cumulative probabilities of infliximab failure-free survival and colectomy-free survival were calculated. Predictors of short-term response and event-free survival were estimated using logistic regression analysis and Cox proportional hazard regression analysis. RESULTS: Seventy-nine patients were included. Fifty-four patients (68.4%) achieved short-term clinical response and 41 patients (51.9%) entered in clinical remission. After a median follow-up of 15 months [interquartile range (IQR) 8-26], 33 patients (41.8%) had infliximab failure. Patients with short-term response had a significantly lower adjusted rate of infliximab failure [hazard ratio (HR) 0.24, 95% confidence interval (CI) 0.12-0.49; p < 0.001]. During a median follow-up of 24 months (IQR 13-34), 9 patients (11.4%) needed colectomy. Short-term response was identified as a predictor of colectomy avoidance (HR 0.14; 95% CI 0.03-0.69; p < 0.007). CONCLUSIONS: In UC patients who lost response to infliximab during maintenance, infliximab dose escalation enabled recovery of short-term response in nearly 70% of patients. In the long term, 58% of patients maintained sustained clinical benefit, and 9 of 10 avoided colectomy. Short-term response was associated with an 86% reduction in the relative risk of colectomy.

HLA-DQA1*05 Not Associated With Ustekinumab Loss of Response and Antidrug Antibodies in Ulcerative Colitis and Crohn's Disease Patients.

It is unknown if inflammatory bowel disease patients carrying the HLA-DQA1*05 allele have a greater risk of immunogenicity to ustekinumab. We observed that ustekinumab-treated patients carrying the allele did not have increased immunogenicity or reduced efficacy/serum ustekinumab concentrations vs noncarriers.

Incidence and Management of Recurrence in Patients with Crohn's Disease Who Have Undergone Intestinal Resection: The Practicrohn Study.

BACKGROUND: More than 50% of patients with Crohn's disease require intestinal resection at least once. Postoperative recurrence (POR) is almost uniform if prophylactic treatment is not started early. Endoscopic monitoring is generally advised. We studied the incidence and management of recurrence in patients who had undergone intestinal resection. METHODS: Practicrohn was an observational retrospective study performed in 26 Spanish hospitals including patients aged ≥18 years who underwent Crohn's disease-related ileocolonic resection between January 2007 and December 2010. We recorded preventive treatments, the incidence of clinical recurrence in daily practice, and associated risk factors. RESULTS: The study population comprised 314 patients. Median (interquartile range) time from diagnosis to surgery was 6 (1-12) years. Prophylaxis for POR was administered to 208 patients (68%). Endoscopy was performed in 143 (46%) patients the first year after surgery. Clinical POR was detected in 97 patients (31%) after a median 315 (65-748) days. The cumulative probability of clinical POR was 16%, 27%, and 31% at 1, 3, and 5 years, respectively, being higher among patients not receiving immunomodulators as compared to those who received prophylaxis (P = 0.014). Forty-five patients (14%) required reoperation at 5 years after a median time from the first intervention of 228 (133-527) days. CONCLUSIONS: In this real-life study, up to one-third of patients with Crohn's disease did not start preventive therapy after intestinal resection, and almost half of them were not endoscopically monitored as recommended. In this setting, 30% of patients developed clinical POR within the first 5 years after surgery, thus indicating that there is room for improvement.