Tumor necrosis factor-α (TNFα) antagonists have advanced the management of inflammatory bowel diseases patients leading to an improvement of patient's quality of life with the reduction of number of surgeries and hospitalizations. Despite these advances, many patients do not respond to the induction therapy (primary non-response-PNR) or lose response during the treatment (secondary loss of response-LOR). In this paper we will provide an overview of the definition, epidemiology and risk factors for PNR and LOR, as well as discuss the therapeutic options for managing LOR.

Loss of Response to Anti-TNFs: Definition, Epidemiology, and Management.

American Gastroenterological Association Institute Guideline on Therapeutic Drug Monitoring in Inflammatory Bowel Disease

https://www.cghjournal.org/article/S1542-3565(15)01492-5/pdf

Optimizing Anti-TNF-α Therapy: Serum Levels of Infliximab and Adalimumab Are Associated With Mucosal Healing in Patients With Inflammatory Bowel Diseases

Background:The contemporary management of ambulatory ulcerative colitis (UC) continues to be challenging with ∼20% of children needing a colectomy within childhood years. We thus aimed to standardize daily treatment of pediatric UC and inflammatory bowel diseases (IBD)-unclassified through d

/pdf/management-of-paediatric-ulcerative-colitis-part-1-4jrh6ti3dq.pdf

Management of Paediatric Ulcerative Colitis, Part 1: Ambulatory Care-An Evidence-based Guideline From European Crohn's and Colitis Organization and European Society of Paediatric Gastroenterology, Hepatology and Nutrition.

https://www.cghjournal.org/article/S1542-3565(13)01050-1/pdf

Association Between Pharmacokinetics of Adalimumab and Mucosal Healing in Patients With Inflammatory Bowel Diseases

SummaryBackground
Adalimumab is an effective treatment for Crohn's disease (CD). Anti-adalimumab antibodies (AAA) and low trough serum drug concentrations have been implicated as pre-disposing factors for treatment failure.

Aims
To assess adalimumab and AAA serum levels, and to examine their association and discriminatory ability with clinical response and serum C-reactive protein (CRP).

Methods
We performed a cross-sectional study using trough sera from adalimumab-treated CD patients. Demographical data, Montreal classification, treatment regimen and clinical status were recorded. Serum adalimumab, AAA and CRP were measured. Receiver operating characteristic analysis and a multivariate regression model were performed to find drug and antibody thresholds for predicting disease activity at time of serum sampling.

Results
One hundred and eighteen trough serum samples were included from 71 patients. High adalimumab trough serum concentration was associated with disease remission (Area Under Curve 0.748, P < 0.001). A cut-off drug level of 5.85 μg/mL yielded optimal sensitivity, specificity and positive likelihood ratio for remission prediction (68%, 70.6% and 2.3, respectively). AAA were inversely related with adalimumab drug levels (Spearman's r = −0.411, P < 0.001) and when subdivided into categorical values, positively related with disease activity (P < 0.001). High drug levels and stricturing vs. penetrating or inflammatory phenotype, but not AAA levels, independently predicted disease remission in a multivariate logistic regression model.

Conclusions
Adalimumab drug levels were inversely related to disease activity. High levels of anti-adalimumab antibodies were positively associated with disease activity, but this association was mediated mostly by adalimumab drug levels.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/apt.12869

Adalimumab drug and antibody levels as predictors of clinical and laboratory response in patients with Crohn's disease

P517 Evaluating Adalimumab drug and antibody levels as predictors of clinical and laboratory response in Crohn's disease patients

Background: Crohn’s disease (CD) and ulcerative colitis (UC) are chronic, immune-mediated inflammatory bowel diseases (IBD) affecting millions of people worldwide. IBD therapies, designed for continuous immune suppression, often render patients more susceptible to infections. The effect of the immune suppression on the risk of coronavirus disease-19 (COVID-19) is not fully determined yet. Objective: To describe COVID-19 characteristics and outcomes and to evaluate the association between IBD phenotypes, infection outcomes and immunomodulatory therapies. Methods: In this multi-center study, we prospectively followed IBD patients with proven COVID-19. De-identified data from medical charts were collected including age, gender, IBD type, IBD clinical activity, IBD treatments, comorbidities, symptoms and outcomes of COVID-19. A multivariable regression model was used to examine the effect of immunosuppressant drugs on the risk of infection by COVID-19 and the outcomes. Results: Of 144 IBD patients, 104 (72%) were CD and 40 (28%) were UC. Mean age was 32.2 ± 12.6 years. No mortalities were reported. In total, 94 patients (65.3%) received biologic therapy. Of them, 51 (54%) at escalated doses, 10 (11%) in combination with immunomodulators and 9 (10%) with concomitant corticosteroids. Disease location, behavior and activity did not correlate with the severity of COVID-19. Biologics as monotherapy or with immunomodulators or corticosteroids were not associated with more severe infection. On the contrary, patients receiving biologics had significantly milder infection course (p = 0.001) and were less likely to be hospitalized (p = 0.001). Treatment was postponed in 34.7% of patients until recovery from COVID-19, without consequent exacerbation. Conclusion: We did not witness aggravated COVID-19 outcomes in patients with IBD. Patients treated with biologics had a favorable outcome.

/pdf/covid-19-in-patients-with-inflammatory-bowel-disease-the-3vr2iqoc.pdf

COVID-19 in Patients with Inflammatory Bowel Disease: The Israeli Experience

Su1572: PATTERNS OF MEDICATION USE IN ELDERLY-ONSET INFLAMMATORY BOWEL DISEASE (IBD) - A POPULATION BASED STUDY FROM THE EPIDEMIOLOGIC DATABASE OF THE ISRAEL IBD RESARCH NUCLEUS (EPI-IIRN)

D. Ben Hur

Papers

Adalimumab drug and antibody levels as predictors of clinical and laboratory response in patients with Crohn's disease

P517 Evaluating Adalimumab drug and antibody levels as predictors of clinical and laboratory response in Crohn's disease patients

COVID-19 in Patients with Inflammatory Bowel Disease: The Israeli Experience

Su1572: PATTERNS OF MEDICATION USE IN ELDERLY-ONSET INFLAMMATORY BOWEL DISEASE (IBD) - A POPULATION BASED STUDY FROM THE EPIDEMIOLOGIC DATABASE OF THE ISRAEL IBD RESARCH NUCLEUS (EPI-IIRN)

Tu1068: THE ASSOCIATION BETWEEN LOW BODY-MASS INDEX AND SERIOUS ENDOSCOPIC ADVERSE EVENTS