Adalimumab Concentration Changes After Dose Escalation in Inflammatory Bowel Disease.

BACKGROUND: Dose escalation of adalimumab (ADA) for loss or response in inflammatory bowel disease (IBD) is a common practice. Recent data suggest improved outcomes with an ADA concentration of 12 mcg/mL, but limited data are available on the ability to achieve a target concentration. The aim of this study was to determine the expected change in serum ADA concentration after a dose escalation performed every 7 days in patients with IBD. METHODS: A retrospective cohort of patients with IBD receiving ADA was divided into every fourteen-day dosing, every 7-day dosing, and dose escalation (ie, q14 to q7 day dosing). The primary outcome was the change in ADA concentration. Multiple logistic regression was performed to identify predictors of achieving a target ADA concentration of ≥12 mcg/mL. RESULTS: Overall, 380 patients were identified, of whom 200 underwent dose escalation, 100 remained on q14 days dosing, and 80 were maintained on q7 day dosing. After dose escalation, the mean ADA concentration increased by 5.5 mcg/mL (P < 0.0001). After dose escalation, a significant proportion of patients achieved an ADA concentration ≥12 mcg/mL (P = 0.0019), as well as clinical remission (P = 0.0053). Based on multiple logistic regression, age of <46 years [odds ratio (OR): 2.4; 95% confidence interval (CI): 1.3, 4.6; P < 0.01], body mass index of <29 (OR: 0.21; 95% CI: 0.1, 0.5; P < 0.0001), and initial ADA concentration of ≥3.0 mcg/mL were found to be associated with a target ADA concentration ≥12 mcg/mL (OR: 4.76; 95% CI: 2.3, 9.7; P < 0.0001). CONCLUSIONS: The average expected increase in serum ADA concentration after dose escalation from q14 to q7 days was 5.5 mcg/mL. The initial ADA concentration, age, and body mass index may influence the ability to achieve a target ADA concentration after dose escalation.

Significance of serrated epithelial change in inflammatory bowel disease.

OBJECTIVES: The clinical significance of hyperplastic polyp-like histologic changes in random biopsy samples ('serrated epithelial change' or SEC) from patients with inflammatory bowel disease (IBD) remains uncertain, with some studies suggesting an increased risk of dysplasia and even carcinoma. Controlled studies are few. We studied the significance of SEC on the development of dysplasia in follow-up surveillance of IBD patients in our system. METHODS: We identified 94 IBD patients with SEC and 187 IBD patients without SEC identified in index biopsy samples, and retrospectively collated results of follow-up surveillance samples in each group, with the development of dysplasia and/or adenocarcinoma as study endpoints. RESULTS: IBD patients with SEC had a 12.8% likelihood of developing dysplasia of any type within IBD-affected areas vs a 4.3% likelihood in non-SEC patients (follow-up in the 1-4 year range for each group). This was significant in univariate analysis (p = 0.013) but not in multivariate analysis, likely due to increased frequency of follow-up sampling in the SEC patients. One cancer developed in each group (p = NS). CONCLUSION: Our data, in the context of other studies, neither prove nor conclusively exclude an increased risk of dysplasia in IBD patients with SEC. But cancer risk appears low and continued surveillance at usual intervals seems reasonable.

Correction: Anti-TNF and thiopurine therapy in pregnant IBD patients does not significantly alter a panel of B-cell and T-cell subsets in 1-year-old infants.

The original version of this article contained an error in Fig. 2, in which part of the text in the legend was omitted. This has now been corrected in the PDF and HTML versions of the paper.Furthermore, the figure legends were missing for the Supplementary figure files. The HTML has now been updated to include a corrected version of the Supplementary Information.

Anti-TNF and thiopurine therapy in pregnant IBD patients does not significantly alter a panel of B-cell and T-cell subsets in 1-year-old infants.

OBJECTIVES: Infants exposed to combination therapy with anti-tumor necrosis factor (anti-TNF) agents and thiopurines may exhibit increased infections at 1 year of age compared to unexposed infants. We hypothesized that this increased risk of infection is due to abnormal development of the newborn immune system. METHODS: We immunophenotyped B-cell and T-cell subsets using multiparameter flow cytometry in 1-year-old infants whose mothers were exposed to therapeutic agents for IBD. We analyzed samples from infants exposed to infliximab (IFX) or adalimumab (ADA) monotherapy (IFX/ADA, n = 11), certolizumab pegol (CZP) monotherapy (CZP, n = 4), IFX or ADA plus thiopurine combination therapy (IFX/ADA + IM, n = 4), and CZP plus thiopurine combination therapy (CZP + IM, n = 2). RESULTS: Percentages of B cells, CD4+ T helper cells, T regulatory cells (Tregs), and CD8+ cytotoxic T cells, were similar among the groups. Infants exposed to combination therapy (IFX/ADA + IM) exhibited trends toward fewer CD27+ B cells, switched memory B cells, plasmablasts, interferon gamma (IFNγ)-producing CD4+ and CD8+ T cells, and CCR5+CD4+ T cells, but these did not reach statistical significance. CONCLUSIONS: Multiparameter immunophenotyping of major B-cell and T-cell subsets suggests that the adaptive newborn immune system develops largely unaltered after exposure to combination therapy as compared to anti-TNF monotherapy.

Long-term durability of Crohn's disease treatment with infliximab.

BACKGROUND: There is a paucity of data providing insight into the durability of Crohn's disease treatment with infliximab for periods longer than 12 months. Our aim was to assess the long-term durability of infliximab therapy. MATERIALS AND METHODS: A total of 198 Crohn's patients under a maintenance regimen with infliximab, with at least a 30-month follow-up, were evaluated retrospectively. Long-term response maintenance was estimated using Kaplan-Meier analysis. The effect of specific variables was calculated using logistic regression and proportional hazard regression analyses. RESULTS: Maintenance of response rates at 72 months was estimated to be 66.4% for initial responders and 58.2% for all patients treated. Concurrent immunomodulators enhanced response maintenance in all patients treated, particularly if started >3 months before the initiation of infliximab therapy. Smoking significantly decreased the maintenance of response in initial responders. CONCLUSIONS: Infliximab treatment of Crohn's disease is reasonably durable beyond 12 months. Concurrent immunosuppressive therapy may increase - and smoking may decrease - long-term response maintenance.

Gastrointestinal Manifestations of Non-AIDS Immunodeficiency.

Most primary immunodeficiencies are diagnosed in children and, therefore, are managed by pediatricians and pediatric specialists. Generally, internists and adult gastroenterologists only rarely encounter patients with primary immunodeficiency, and have little or no involvement in actual treatment. However, gastroenterologists should be familiar with primary immunodeficiency because 1) current and future therapy for immunodeficiency will allow more patients to survive into adulthood, 2) some primary immunodeficiencies, particularly common variable immunodeficiency, may have their first clinical manifestation in adolescence or early adulthood, and 3) recently it has been hypothesized that Crohn's disease may be an immunodeficiency. Detailed treatment recommendations are not included in this review, as subspecialists in pediatrics, immunology, and hematology manage such treatments. Of far greater importance, even in this treatment-oriented forum, is the enhancement of our awareness of these disorders.