Prospective Observational Evaluation of the Time-Dependency of Adalimumab Immunogenicity and Drug Concentration in Ulcerative Colitis Patients: the POETIC II Study.

BACKGROUND AND AIMS: Home self-injection of the human anti-tumour necrosis alpha [anti-TNFα] monoclonal adalimumab complicates prospective serial-sampling studies. Although a recent study examined adalimumab levels and immunogenicity in Crohn's disease [CD] patients, prospective real-world data from ulcerative colitis [UC] patients are lacking. METHODS: A three-monthly home-visit programme from induction was established prospectively for UC patients. Clinical scores were determined at each visit, and sera were obtained for assessment of drug and anti-adalimumab antibody levels. Calprotectin was measured using a smartphone-based app. This cohort was compared to a parallel prospective cohort of adalimumab-treated CD patients [POETIC1]. RESULTS: Fifty UC patients starting adalimumab [median follow-up 28 weeks] were compared to 98 adalimumab-treated CD patients [median follow-up 44 weeks]. Only 11/50 UC patients [22%] continued treatment to the end of the follow-up compared with 50/98 [51%] CD patients (odds ratio [OR] = 0.27, p = 0.001). Loss of response was significantly more common in UC patients [OR = 3.2, p = 0.001]. Seventeen patients [34%] in the UC cohort developed anti-adalimumab antibodies, 9/17 [52.9%] as early as week 2. There was no difference between patient cohorts in the overall development of anti-adalimumab antibodies [34% vs 30.6%, respectively, OR = 1.67, p = 0.67], nor was there a difference in early immunogenicity [OR = 1.39, p = 0.35]. There was no difference in low drug levels [<3 µg/mL] between the two cohorts [OR = 0.87, p = 0.83]. CONCLUSIONS: Loss of response to adalimumab therapy was significantly more common in the UC compared to the CD cohort and was driven by a higher rate of non-immunogenic, pharmacodynamic parameters.

Infantile-onset inflammatory bowel disease has variable long-term outcomes.

Objective and aim: Infantile-onset inflammatory bowel disease (IO-IBD), defined as IBD diagnosed at age 2 years or younger, tends to be more severe and refractory to conventional treatment than IBD diagnosed at a later age. However, data about IO-IBD and its long-term follow up are limited. We thus aimed to evaluate the presentation and long-term outcomes of patients with IO-IBD in a retrospective multicenter study. Methods: Medical records of patients diagnosed with IO-IBD in eight medical centers during 2000-2017 with at least 1-year follow up were reviewed. Demographics and disease characteristics at diagnosis including age of onset, disease phenotype and location, surgeries, medical therapy, and comorbid conditions were recorded. Results: Twenty-three patients with IO-IBD (16 males, 70%) were identified and followed for a median (range) of 51.2 (26.0-110.3) months. The mean ages at presentation and at the last follow up were 14 ± 9.8 and 101 ± 77 months, respectively. Six (26%) patients needed ileostomy already at the time of diagnosis and 20 (87%) were treated with corticosteroids. During long-term follow up, remission was achieved in 16 (73%) patients; of whom, 3 (14%) were without medications and 7 (32%) were in remission with the use of 5-aminosalicylic acid only. One patient needed hemicolectomy and one developed a severe EBV related infection. Conclusion: The majority of patients with IO-IBD achieved long-term remission, despite a severe disease presentation at diagnosis. Surgery rate however is high, mainly during the first months from diagnosis.

Outcomes, dosing, and predictors of vedolizumab treatment in children with inflammatory bowel disease (VEDOKIDS): a prospective, multicentre cohort study.

BACKGROUND: Scarce data are available on the use of vedolizumab in children with inflammatory bowel disease (IBD). We aimed to evaluate the safety, effectiveness, and dosing of vedolizumab to induce remission of IBD. METHODS: VEDOKIDS was a paediatric, multicentre, prospective cohort study done in 17 centres in six countries. We report the 14-week outcomes as the first analyses of the planned 3-year follow-up of the VEDOKIDS cohort. Children (aged 0-18 years) with IBD who had commenced vedolizumab were followed up at baseline and at 2, 6, and 14 weeks. Children were managed according to local prescribing practices without standardisation of dosing or criteria for escalation, but the study protocol suggested dosing of 177 mg/m2 body surface area (up to 300 mg maximum). The primary outcome was steroid-free and exclusive enteral nutrition-free remission at 14 weeks, analysed according to the intention-to-treat principle. Serum samples were taken for analysis of drug concentration and faecal calprotectin at baseline, and at 2, 6, and 14 weeks. Adverse events were recorded in real time and classified as severe or non-severe and related or unrelated to vedolizumab. This study is registered with ClinicalTrials.gov, NCT02862132. FINDINGS: Between May 19, 2016, and April 1, 2022, 142 children (76 [54%] girls and 66 [46%] boys; mean age 13·6 years [SD 3·6]) were enrolled. 65 (46%) children had Crohn's disease, 68 (48%) had ulcerative colitis, and nine (6%) had unclassified IBD (those with unclassified IBD were analysed with the ulcerative colitis group). 32 (42% [95% CI 30-54]) of 77 children with ulcerative colitis and 21 (32% [23-45]) of 65 children with Crohn's disease were in steroid-free and exclusive enteral nutrition-free remission at 14 weeks. Median drug concentrations at week 14 were higher in children with ulcerative colitis than in those with Crohn's disease (11·5 µg/mL [IQR 5·5-18·1] vs 5·9 µg/mL [3·0-12·7]; p=0·006). In children who weighed less than 30 kg, the optimal drug concentration associated with steroid-free and exclusive enteral nutrition-free clinical remission was 7 µg/mL at week 14 (area under the curve 0·69 [95% CI 0·41-0·98]), corresponding to a dose of 200 mg/m2 body surface area or 10 mg/kg. 32 (23%) of 142 children reported at least one adverse event, the most common were headache (five [4%]), myalgia (four [3%]), and fever (three [2%]). None of the adverse events were classified as severe, and only two (1%) patients discontinued treatment due to adverse events. INTERPRETATION: Vedolizumab showed good safety and effectiveness at inducing remission in children with IBD at 14 weeks, especially those with ulcerative colitis. Vedolizumab should be considered in children when other approved drug interventions for IBD are unsuccessful. In children who weigh less than 30 kg, vedolizumab should be dosed by the child's body surface area (200 mg/m2) or weight (10 mg/kg). FUNDING: The European Crohn's and Colitis Organization, the European Society for Paediatric Gastroenterology Hepatology and Nutrition, and Takeda.

Video Capsule Endoscopy Has a Minor Long-term Therapeutic Impact on Patients with Iron Deficiency Anemia.

BACKGROUND: One of the main causes of iron deficiency anemia (IDA) is chronic gastrointestinal blood loss. The use of video capsule endoscopy (VCE) after negative bidirectional endoscopy in patients with IDA is controversial. OBJECTIVES: To evaluate the effect of VCE in the management and long-term outcomes of IDA patients. METHODS: A retrospective case-control study was performed on all patients with IDA undergoing VCE over a 5-year period. We compared those with positive findings on VCE to those with normal findings. All participants previously underwent a negative bidirectional endoscopy. RESULTS: We performed 199 VCE examinations; median follow-up time was 4 years (IQR 2-5). Positive findings were identified in 66 patients (diagnostic yield 33.2%). Double balloon enteroscopy or push enteroscopy was performed in eight patients (18.6%); only one was therapeutic. The main therapy in both groups was iron supplementation. There were no significant differences in iron treatment before and after VCE in each group and between groups. Anemia improved in both groups. There was no difference in the level of hemoglobin change between the groups during each year of follow-up compared to the baseline level prior to VCE. Anemia resolved in 15 patients (35%) in the positive VCE group and in 19 (45%) in the negative VCE group (P = 0.33). CONCLUSIONS: Positive findings on VCE led to subsequent endoscopic interventions only in a small percentage of patients with IDA. Anemia improved and resolved equally whether or not there were VCE findings. The main intervention that appears to help IDA is iron supplementation.

Effect of inflammatory bowel disease and related medications on COVID-19 incidence, disease severity, and outcome: the Israeli experience.

OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic raised concerns among inflammatory bowel disease (IBD) patients fearing an increased risk of infection and poor outcomes. We aimed to evaluate the incidence of COVID-19 among IBD patients; its influence on disease severity and outcome; its relationship to medication use and how the pandemic affected IBD management. METHODS: An anonymous questionnaire was posted online to members of the Israel Crohn's Disease and Ulcerative Colitis Foundation (November 2020-January 2021). The questionnaire addressed the course of IBD disease and COVID-19 infection over the past year. RESULTS: Total 2152 IBD patients completed the questionnaire. Of which 104 (4.8%) had been infected with COVID-19, significantly lower than the 'expected' infected cases among the Israeli population (P = 0.033). The median age of participants was 39 years; 60.5% were female. Most patients (75.6%) had no comorbidities other than IBD. No correlation was found between IBD type or disease severity and COVID-19 infection. Most IBD patients reported mild COVID-19 disease, regardless of the type of IBD medications. Multivariable logistic regression analysis revealed that younger age, elevated BMI and diabetes were independent risk factors for COVID-19 infection. IBD treatment methods including 5-aminosalicylic acid, smoking and hypertension were protective factors. In total 25.2% of COVID-19 patients discontinued their IBD treatment, compared to 8.5% of non-COVID-19-infected patients. IBD flares were significantly higher in those who discontinued treatment (P < 0.001). CONCLUSIONS: IBD patients do not have an increased risk for COVID-19, regardless of IBD activity or treatment. Patients should be encouraged to continue effective IBD therapy, including biologics and steroids, to minimize active IBD.

Natural Progression of Helicobacter pylori-Negative Gastritis with Lymphoid Follicles in Children: Prospective Evaluation and Outcome.

BACKGROUND: The association of Helicobacter pylori-negative gastritis with lymphoid follicles (LFs) in children is still unclear. Therefore, we aimed to investigate the natural history and significance of H. pylori-negative gastritis with LFs in children. METHODS: We identified children with histologically proven H. pylori-negative gastritis with LFs between June 2014 and January 2017. The children were invited for a follow-up examination. The clinical, endoscopic, and histological findings of the index esophagogastroduodenoscopy (EGD) were revised and compared to the follow-up findings. RESULTS: A total of 754 children underwent EGD. Among the 48 children diagnosed with H. pylori-negative gastritis, 17 (35.41%) had gastric LFs. Eight agreed to participate in the study. The mean follow-up was 25.58 ± 4.52 (range, 20.53-35.73) months. Three children still had histologic findings of chronic gastritis with LFs. Four children had resolution of the gastritis but still had LFs, and 1 patient had resolution of both the gastritis and LFs. CONCLUSION: LFs were still present in children with H. pylori-negative gastritis after a mean follow-up of 2 years, and in some children, despite resolution of the gastritis. Therefore, this histological finding might be a non-pathological feature in children and does not need any contribution or follow-up.

The inflammatory bowel disease disk application: A platform to assess patients' priorities and expectations from treatment.

OBJECTIVE: Inflammatory bowel disease (IBD) significantly impacts on patients' well-being. Patients' preferences for treatment outcomes do not necessarily fit physicians' goals. We aimed to investigate patients' priorities and expectations from treatment. METHODS: A questionnaire based on the IBD Disk application was distributed to patients through social media. Patient's preferences were assessed by grading the 10 IBD Disk items on a Likert-type scale from 1 to 10. A cluster analysis was used to classify patients into homogeneous subgroups according to their preferred items, using the K-means method. RESULTS: Among the 224 patients, 69.2% had Crohn's disease (CD). Their mean age was (38.9 ± 14.9) years and 62.9% were female. More CD patients compared with those with ulcerative colitis were treated with biologics compared with those with ulcerative colitis (71.0% vs 39.1%, P < 0.001). Most IBD Disk items ranked high in patients' preferences for treatment outcomes. Their leading preference was reducing abdominal pain, which was more prominent in CD patients, followed by regulating defecation and energy. Least important were interpersonal interactions, sexual functions, and body image. Patients were categorized into three clusters. Cluster 3 patients gave lower scores to most items and were characterized by tertiary education (P = 0.001), higher income (P < 0.001), less active disease (P = 0.02), and higher prevalence of successful treatment (P = 0.04). CONCLUSIONS: Patients' preferences for treatment outcomes are influenced by higher education, higher income, rural-dwelling, and disease activity. Better understanding of individual patient's preferences and the factors that affect them might bridge the gap between patients' and physicians' priorities to achieve better teamwork in controlling disease outcomes.

Monitoring Enables Progress: A Nationwide Quality Improvement Program in Children With Crohn Disease.

OBJECTIVES: In this quality improvement program, named quality in pediatric inflammatory bowel disease, we constructed a nation-wide platform that prospectively recorded clinically important quality indicators in pediatric inflammatory bowel diseases (PIBD), aiming at improving clinical management across the country. METHODS: Representatives of all 21 PIBD facilities in Israel formed a Delphi group to select quality indicators (process and outcomes), recorded prospectively over 2 years in children with Crohn's disease 2-18 years of age seen in the outpatient clinics. Monthly anonymized reports were distributed to all centers, allowing comparison and improvement. Trends were analyzed using the Mann-Kendall test, reporting τ (tau) values. RESULTS: The indicators of 3254 visits from 1709 patients were recorded from September 2017 to September 2019 (mean age 14.7 ±â€Š3.1 years, median disease duration 1.8 years (interquartile range 0.69-4.02)). An increase in three of five process indicators was demonstrated: obtaining drug levels of anti-tumor necrosis factor (TNF) (τ = 0.4; P = 0.005), utilization of fecal calprotectin (τ = 0.38; P = 0.008) and bone density testing (τ = 0.45; P = 0.002). Among outcome indicators, three of nine improved as measured during the preceding year: calprotectin <300 µg/mg (τ = 0.35; P = 0.015), and "resolution of inflammation" defined as a composite of endoscopy, imaging and fecal calprotectin (τ = 0.39; P = 0.007). Endoscopic healing reached borderline significance (τ = 0.28; P = 0.055). An increase in the use of biologics throughout the study was observed (τ = 0.47; P = 0.001) with a concurrent decrease in the use of immunomodulators (τ = -0.47; P = 0.001). CONCLUSIONS: Quality improvement nationwide programs can be implemented with limited resources while facilitating standardization of care, and may be associated with improvements in measured indicators.

The Effect of Adalimumab Treatment on Linear Growth in Children With Crohn Disease: A Post-hoc Analysis of the PAILOT Randomized Control Trial.

OBJECTIVES: Growth impairment is common in children with Crohn disease (CD). We aimed to assess the effect of adalimumab (ADL) treatment on linear growth in children with CD in a post-hoc analysis of the Pediatric Crohn's Disease AdalImumab Level-based Optimization Treatment randomized controlled trial. METHODS: Children 6 to 17 years who responded to ADL induction were assessed consecutively for anthropometric parameters. Associations of these parameters with disease characteristics and disease activity were analyzed. RESULTS: Overall, 66 patients completed 72 weeks of follow-up (25% girls, mean age of 15.6 ±â€Š2.5 years). Median (interquartile range [IQR]) height z score improved from -0.6 (-1.6-0.15) at baseline to -0.33 (-1.3-0.5) at week 72 (P = 0.005) with lesser improvement in patients with perianal disease. Similar effect was noted in children with growth potential (boys younger than 16 years, girls younger than 14 years). Median (IQR) height velocity standard deviation was -0.32 (-1.5-0.8) at week 26, and +0.11 (-1.1-1.3) at week 72. Median weight z score increased from -0.54 (-1.2-0.15) to -0.1 (-0.9-0.6), P < 0.001 and body mass index from -0.4 (-1.0-0.5) to 0.0 (-0.8-0.9), P = 0.005. Pediatric CD activity index and erythrocyte sedimentation rate at week 4 correlated negatively with height z score changes (P = 0.043 and P = 0.048, respectively), whereas sustained clinical and biologic remission (week 4-72) were positively associated with changes in height z scores. Significant improvement in linear growth was predicted by lower pediatric CD activity index and erythrocyte sedimentation rate at the end of induction and sustained clinical remission (P = 0.05) and sustained normal C-reactive protein (P = 0.001) at all visits. CONCLUSION: In children with moderate-to-severe CD, ADL treatment had a significant effect on linear growth, with normalization of weight and body mass index (clinicaltrials.gov no: NCT02256462).

The Safety and Feasibility of a New Through-the-scope Balloon-assisted Enteroscopy in Children.

OBJECTIVES: Small bowel involvement in Crohn disease (CD) is clinically important for diagnosis and treatment. Single and double-balloon enteroscopy have already become important diagnostic tools in such cases. The on-demand NaviAid AB device enables deep advancement into the small bowel, using an anterograde or retrograde approach. In adults, this procedure is feasible, safe, and rapid. This work aimed to assess the safety and feasibility of NaviAid AB enteroscopy in pediatric patients. METHODS: Single-center, prospective study using the through-the-scope balloon-assisted-enteroscopy (TTS-BAE) NaviAid AB device for the evaluation of the small bowel in children with suspected or known inflammatory bowel disease (IBD). The system consists of a single-use balloon catheter inserted through the instrument channel of a standard colonoscope. It consists of an inflation/deflation system (NaviAid SPARK), which is inflated to anchoring pressure. The repetitive push-pull technique enables the advancement of the colonoscope along the small intestine. RESULTS: Fifty analyzed endoscopic procedures (30 retrograde, 20 anterograde) were performed in 34 children (52.9% boys, mean age 13.7 years). Average maximal depth of insertion (MDI), advancement depth using the NaviAid AB and average total procedure time were 138 cm (range 100-190 cm), 81 cm (range 40-120 cm), and 12.8 minutes (range 7.3-19.0 minutes), respectively, for the anterograde approach and 143 cm (range 100-170 cm), 64 cm (range 20-95 cm), and 21.9 minutes (range 13.9-32.0 minutes), respectively, for the retrograde approach. No serious or device-related adverse events were reported. CONCLUSIONS: NaviAid AB enteroscopy in children is safe, feasible, and enables assessment of the small intestine in a short period of time.

Is administration of proton pump inhibitors in functional dyspepsia worth the risk of developing gastric cancer: a Markov model to bridge the gap between scientific evidence and clinical practice.

OBJECTIVE: To formulate a decision analysis model based on recently published data that addresses the dilemma, whether improvement in quality of life rationalises continued proton pump inhibitors (PPI) use despite the risk of gastric cancer (GC) in patients with functional dyspepsia (FD). DESIGN: A Markov model consisting of an initial decision regarding treatment with PPI (denoting it by PPI strategy) or any other treatment without PPI (denoting it by placebo strategy) was designed. DATA SOURCES: Data from prospective cross-sectional studies indicating risk stratification for GC after the use of PPI, combined with a Markov model that comprised the following states: Live, GC stages 1-4, Death. OUTCOME MEASURES: The primary outputs included quality-adjusted life years (QALYs) and life expectancy (LE). The improvement in utility in FD without PPI as compared with PPI use was tested (PPI vs placebo strategies). Sensitivity analyses were performed to evaluate the robustness of the model and address uncertainty in the estimation of model parameters. SETTING: We considered only patients whose symptoms were relieved with PPIs and thus, had a better quality of life compared with patients who did not receive PPIs. RESULTS: The base case model showed that PPIs compared with placebo decreased LE by 58.4 days with a gain of 2.1 QALY. If utility (quality of life of patients with FD using PPI compared with patients with FD without PPI) improved by more than 0.8%, PPI use is considered better than placebo. Older patients benefited less from PPI treatment than did younger patients. CONCLUSION: To bridge the gap between evidence and decision making, we found that even a small improvement in the QALY justified continuing PPI treatment.

Early Surgery Versus Biologic Therapy in Limited Nonstricturing Ileocecal Crohn's Disease-A Decision-making Analysis.

BACKGROUND: Surgery is the preferred option for patients with symptomatic localized fibrostenotic ileocecal Crohn's disease (CD) but not for those with predominantly active inflammation without obstruction. The benefit of early surgery in patients with a limited nonstricturing ileocecal CD over biologic treatment is still a debate. OBJECTIVE: Our objective is to formulate a decision analysis model based on recently published data to explore whether early surgery in patients with limited nonstricturing CD is preferred over biologic treatment. METHODS: We constructed a Markov model comparing 2 strategies of treatment: (1) early surgery vs (2) biologic treatment. To estimate the quality-adjusted life years (QALYs) and the costs in each strategy, we simulated 10,000 virtual patients with the Markov model using a Monte Carlo simulation 100 times. Sensitivity analyses were performed to evaluate the robustness of the model and address uncertainties in the estimation of model parameters. RESULTS: The costs were $29,457 ± $407 and $50,382 ± $525 (mean ± SD) for early surgery strategy and biologic treatment strategy, respectively. The QALY was 6.24 ± 0.01 and 5.81 ± 0.01 for early surgery strategy and biologic treatment strategy, respectively. CONCLUSION: The strategy of early surgery dominates (higher QALY value [efficacy] and less cost) compared with the strategy of biologic treatment in patients with limited ileocecal CD.

Combination Therapy of Adalimumab With an Immunomodulator Is Not More Effective Than Adalimumab Monotherapy in Children With Crohn's Disease: A Post Hoc Analysis of the PAILOT Randomized Controlled Trial.

BACKGROUND: The PAILOT trial was a randomized controlled trial aimed to evaluate proactive vs reactive therapeutic drug monitoring in children with Crohn's disease (CD) treated with adalimumab. Our aim in this post hoc analysis of the PAILOT trial was to assess the efficacy and safety of adalimumab combination treatment in comparison with monotherapy at week 72 after adalimumab induction. METHODS: Participants were children 6-17 years old, biologic naïve, with moderate to severe CD, who responded to adalimumab induction at week 4. Patients receiving immunomodulators at baseline maintained a stable dose until week 24; patients could then discontinue immunomodulators. At each visit, patients were assessed for disease index, serum biomarkers, fecal calprotectin, adalimumab trough concentration, and anti-adalimumab antibodies. RESULTS: Out of the 78 patients (29% female; mean age, 14.3 ± 2.6 years), 34 patients (44%) received combination therapy. During the study period, there was no significant difference in the rates of sustained corticosteroid-free clinical remission (25/34, 73%, vs 28/44, 63%; P = 0.35) or sustained composite outcome of clinical remission, C-reactive protein ≤0.5 mg/dL, and calprotectin ≤150 µg/g (10/34, 29%, vs 14/44, 32%; P = 0.77) between the combination group and the monotherapy group, respectively. Clinical and biological outcomes did not differ between the proactive and reactive subgroups within the combination and monotherapy groups. Adalimumab trough concentrations and immunogenicity were not significantly different between groups. The rate of serious adverse events was not significantly different between groups but was numerically higher in the monotherapy group. CONCLUSIONS: Combination therapy of adalimumab and an immunomodulator was not more effective than adalimumab monotherapy in children with CD (ClinicalTrials.gov No. NCT02256462).

Proactive Monitoring of Adalimumab Trough Concentration Associated With Increased Clinical Remission in Children With Crohn's Disease Compared With Reactive Monitoring.

BACKGROUND & AIMS: Proactive monitoring of drug trough concentrations and antibodies against drugs might help determine whether patients are likely to respond to treatment and increase efficacy. We investigated whether proactive drug monitoring is associated with higher rates of clinical remission in pediatric patients with Crohn's disease (CD). METHODS: We performed a nonblinded, randomized controlled trial of 78 children with CD (6-18 years old; 29% female; mean age, 14.3 ± 2.6 years) who had not received prior treatment with a biologic agent but had responded to adalimumab induction therapy, under scheduled monitoring of clinical and biologic measures (based on clinical factors and levels of C-reactive protein and fecal calprotectin), at pediatric gastroenterology units in Israel from July 2015 through December 2018. The patients were randomly assigned to groups that received proactive monitoring (trough concentrations measured at weeks 4 and 8 and then every 8 weeks until week 72, n = 38) or reactive monitoring (physicians were informed of trough concentrations after loss of response, n = 40). In both groups, doses and intervals of adalimumab were adjusted to achieve trough concentrations of 5 µg/mL. The primary endpoint was sustained corticosteroid-free clinical remission at all visits (week 8 through week 72). RESULTS: The primary endpoint was achieved by 31 children (82%) in the proactive group and 19 children (48%) in the reactive group (P = .002). Sixteen patients in the proactive monitoring group (42%) achieved a composite outcome of sustained corticosteroid-free remission, C-reactive protein ≤0.5 mg/dL, and level of fecal calprotectin ≤150 µg/g compared with 5 patients in the reactive monitoring group (12%) (P = .003). By week 72 of treatment, 33 patients in the proactive monitoring group had received adalimumab intensification (87%) compared with 24 patients in the reactive monitoring group (60%) (P = .001). CONCLUSIONS: In a randomized controlled trial of pediatric patients with CD, we found that proactive monitoring of adalimumab trough concentrations and adjustment of doses and intervals resulted in significantly higher rates corticosteroid-free clinical remission than reactive monitoring (measuring trough concentration after loss of response). Clinicaltrials.gov no.: NCT02256462.

Sense of coherence in people with and without inflammatory bowel diseases - is there a difference?

BACKGROUND AND AIMS: Sense of coherence (SOC) is a theoretical concept reflecting a person's resources and orientation, which enable individuals to cope with stressors in a health-promoting manner. In several multifactorial chronic diseases, such as diabetes mellitus and systemic lupus erythematosus, SOC was correlated with disease development. It was also related with the emotional distress in patients with inflammatory bowel disease (IBD).The aim of this study was to investigate the possible correlation between low SOC scores and the presence of IBD. METHODS: A total of 183 Crohn's disease (CD) and 71 ulcerative colitis (UC) patients completed questionnaires including demographic data and the 13 items for the SOC questionnaire. The IBD patients were matched to 124 healthy people according to age, gender, education, employment status and marital status. RESULTS: In the CD cohort, 96 patients were matched to the healthy cohort according to the propensity score value, and in the UC cohort 57 were matched. Patients with Crohns' disease had a median SOC score of 63 (IQR 56-71), and healthy matching controls of 62.5 (IQR 55.25- 68.75) p=0.369. Patients with ulcerative patients had a median SOC score of 66 (IQR 56-73) and healthy controls 62 (IQR 55-69) p=0.354. CONCLUSIONS: In our study SOC was not related to the development of IBD. The question of whether SOC is associated with the development of chronic disease and particularly with IBD remains open.

Prospective Observational Evaluation of Time-Dependency of Adalimumab Immunogenicity and Drug Concentrations: The POETIC Study.

OBJECTIVES: Adalimumab is usually self-injected at home, making prospective serial-sampling studies challenging and scarce. This has led to a gap in knowledge about evolution of anti-adalimumab antibodies (AAAs) over time and its correlation with clinical and inflammatory outcomes. METHODS: A program for home visits by physicians at induction, every 3 months and at event of relapse, was established prospectively for Crohn's disease (CD) patients. At each visit, patients' clinical scores were determined and sera were obtained for C-reactive protein, drug, and AAA levels. This cohort was compared to a parallel prospective cohort of infliximab-treated CD patients. In a subgroup of 29 patients, trough and in-between-trough levels were compared, to elucidate the importance of timing of sampling during the injection cycle. RESULTS: Ninety-eight CD patients starting adalimumab were prospectively followed (median follow-up 44 weeks) and 621 serum samples were analyzed. Thirty-three patients (32%) developed AAA; 18/33 (55%) of them as early as week 2, and 26/33 (79%) by week 14. Induction period AAAs were strongly associated with primary non-response (odds ratio (OR) = 5.4, 95% confidence interval (CI): 1.6-17.8, p = 0.005). As compared to antibodies-to-infliximab (ATI), AAA formation rate over time was significantly lower (p = 0.01) and AAA were much more specific-85% of AAA events were associated with loss-of-response compared with 58% rate for ATI (p = 0.01). In 29 patients sampled serially during an injection cycle, levels of drug and AAA seemed comparable between four time-points during a single cycle both in patients with or without AAA (n = 8, n = 21, respectively). CONCLUSIONS: When followed prospectively and serially, AAAs are found to arise earlier than previously appreciated and their impact may be more pronounced for primary rather than secondary, non-response. Drug and AAA levels were similar both at trough and in-between injections, enabling to simplify therapeutic drug monitoring of adalimumab.

Expression of Duodenal Iron Transporter Proteins in Diabetic Patients with and without Iron Deficiency Anemia.

The role of iron transport proteins in the pathogenesis of anemia in patients with diabetes mellitus (T2DM) is still unclear. We investigated the expression of duodenal transporter proteins in diabetic patients with and without iron deficiency anemia (IDA). Methods. Overall, 39 patients were included: 16 with T2DM and IDA (group A), 11 with T2DM without IDA (group B), and 12 controls (group C). Duodenal mucosal expression of divalent metal transporter 1 (DMT1), ferroportin 1 (FPN), hephaestin (HEPH), and transferrin receptor 1 (TfR) was evaluated by Western blotting. Chronic disease activity markers were measured as well. Results. FPN expression was increased in group A compared to group B and controls: 1.17 (0.72-1.46), 0.76 (0.53-1.04), and 0.71 (0.64-0.86), respectively (p = 0.011). TfR levels were over expressed in groups A and B compared to controls: 0.39 (0.26-0.61), 0.36 (0.24-0.43), and 0.18 (0.16-0.24), respectively, (p = 0.004). The three groups did not differ significantly with regard to cellular HEPH and DMT1 expression. The normal CRP and serum ferritin levels, accompanied with normal FPN among diabetic patients without IDA, do not support the association of IDA with chronic inflammatory state. Conclusion. In patients with T2DM and IDA, duodenal iron transport protein expression might be dependent on body iron stores rather than by chronic inflammation or diabetes per se.

Corrigendum to "Expression of Duodenal Iron Transporter Proteins in Diabetic Patients with and without Iron Deficiency Anemia".

[This corrects the article DOI: 10.1155/2018/7494821.].

Cost effectiveness of routine duodenal biopsies in iron deficiency anemia.

AIM: To investigate the cost effectiveness of routine small bowel biopsies (SBBs) in patients with iron deficiency anemia (IDA) independent of their celiac disease (CD) serology test results. METHODS: We used a state transition Markov model. Two strategies were compared: routine SBBs during esophagogastroduodenoscopy (EGD) in all patients with IDA regardless their celiac serology status (strategy A) vs SBBs only in IDA patients with positive serology (strategy B). The main outcomes were quality adjusted life years (QALY), average cost and the incremental cost effectiveness ratio (ICER). One way sensitivity analysis was performed on all variables and two way sensitivity analysis on selected variables were done. In order to validate the results, a Monte Carlo simulation of 100 sample trials with 10, and an acceptability curve were performed. RESULTS: Strategy A of routine SBBs yielded 19.888 QALYs with a cost of $218.10 compared to 19.887 QALYs and $234.17 in strategy B. In terms of cost-effectiveness, strategy A was the dominant strategy, as long as the cost of SBBs stayed less than $67. In addition, the ICER of strategy A was preferable, providing the cost of biopsy stays under $77. Monte Carlo simulation demonstrated that strategy A yielded the same QALY but with lower costs than strategy B. CONCLUSION: Our model suggests that EGD with routine SBBs is a cost-effective approach with improved QALYs in patients with IDA when the prevalence of CD is 5% or greater. SBBs should be a routine screening tool for CD among patients with IDA, regardless of their celiac antibody status.

Genetic and electrophysiological characteristics of recurrent acute pancreatitis.

OBJECTIVES: The aim was to present the workup of patients with acute recurrent pancreatitis (ARP) for genetic analysis and electrophysiological testing. METHODS: Patients with ARP with unknown etiology were referred for genetic testing and evaluation of cystic fibrosis transmembrane conductor regulator (CFTR) function by nasal potential difference (NPD) testing. RESULTS: A total of 67 patients were evaluated. The mean age was 23 ±â€Š17 years (median 17.0 years, range 1.5-72 years); 90% were Jewish and 10% Arab. Ten (15%) patients carried PRSS1 gene mutation (K23R(7), R122H(2), and D21A(1)). One patient had K172E/- (chymotrypsin C [CTRC]) mutation, 1 had I42M (serine protease inhibitor Kazal type 1 [SPINK1])/V235I (CTRC) together with ΔF508/5T, 1 patient had R67H (SPINK1)/V235I (CTRC), and 1 patient had V235I (CTRC)/-. Ten of 67 (15%) patients submitted for CFTR gene testing carried mutations (ΔF508/L997F, ΔF508/5T(11TG), W1282/5T(12TG), W1282X/Y1014C, ΔF508/R31C, R117H/-, R117H/Y1014C, D1152H/-, 5T(11TG)/-, and L997F/-). Fifty-four (80%) patients underwent sweat testing. Of these, 5 had sweat chloride ≥60 mEq/L, and 22 patients had sweat chloride from 40 to 60 mEq/L. Of the 56 (83%) patients had nasal potential difference testing, 4 (6%) with abnormal results. CONCLUSIONS: One-third (34%) of patients with ARP carry mutations for hereditary pancreatitis including rare mutations (K23R), and 12.5% have evidence of cftr mutations and 10% had CFTR dysfunction underscoring the importance of genetic and functional workup of these patients.