Comparative Acceptability of Therapeutic Maintenance Regimens in Patients With Inflammatory Bowel Disease: Results From the Nationwide ACCEPT2 Study.

BACKGROUND: Owing to growing number of therapeutic options with similar efficacy and safety, we compared the acceptability of therapeutic maintenance regimens in inflammatory bowel disease (IBD). METHODS: From a nationwide study (24 public or private centers), IBD patients were consecutively included for 6 weeks. A dedicated questionnaire including acceptability numerical scales (ANS) ranging from 0 to 10 (highest acceptability) was administered to both patients and related physicians. RESULTS: Among 1850 included patients (65.9% with Crohn's disease), the ANS were 8.68 ± 2.52 for oral route (first choice in 65.8%), 7.67 ± 2.94 for subcutaneous injections (first choice in 21.4%), and 6.79 ± 3.31 for intravenous infusions (first choice in 12.8%; P < .001 for each comparison). In biologic-naïve patients (n = 315), the most accepted maintenance regimens were oral intake once (ANS = 8.8 ± 2.2) or twice (ANS = 6.9 ± 3.4) daily and subcutaneous injections every 12 or 8 weeks (ANS = 7.9 ± 3.0 and ANS = 7.2 ± 3.2, respectively). Among 342 patients with prior exposure to subcutaneous biologics, the preferred regimens were subcutaneous injections (≥2 week-intervals; ANS between 9.1 ± 2.3 and 8.1 ± 2.7) and oral intake once daily (ANS = 7.7 ± 3.2); although it was subcutaneous injections every 12 or 8 weeks (ANS = 8.4 ± 3.0 and ANS = 8.1 ± 3.0, respectively) and oral intake once daily (ANS = 7.6 ± 3.1) in case of prior exposure to intravenous biologics (n = 1181). The impact of usual therapeutic escalation or de-escalation was mild (effect size <0.5). From patients' acceptability perspective, superiority and noninferiority cutoff values should be 15% and 5%, respectively. CONCLUSIONS: Although oral intake is overall preferred, acceptability is highly impacted by the rhythm of administration and prior medication exposures. However, SC treatment with long intervals between 2 injections (≥8 weeks) and oral intake once daily seems to be the most accepted modalities.

Considering both the route of medication delivery and the interval between 2 administrations, we observed a strong impact of patients' experience regarding previous treatments. The most accepted maintenance regimens were subcutaneous injections with interval ≥8 weeks and oral intake.

Bariatric Surgery in Patients With Inflammatory Bowel Disease: A Case-Control Study from the GETAID.

BACKGROUND: The prevalence of obesity and the number of bariatric surgeries in both the general population and in patients with inflammatory bowel disease (IBD) have increased significantly in recent years. Due to small sample sizes and the lack of adequate controls, no definite conclusions can be drawn from the available studies on the safety and efficacy of bariatric surgery (BS) in patients with IBD. Our aim was to assess safety, weight loss, and deficiencies in patients with IBD and obesity who underwent BS and compare findings to a control group. METHODS: Patients with IBD and a history of BS were retrospectively recruited to centers belonging to the Groupe d'Etude Thérapeutique des Affections Inflammatoires du Tube Digestif (GETAID). Patients were matched 1:2 for age, sex, body mass index (BMI), hospital of surgery, and type of BS with non-IBD patients who underwent BS. Complications, rehospitalizations, weight, and deficiencies after BS were collected in cases and controls. RESULTS: We included 88 procedures in 85 patients (64 Crohn's disease, 20 ulcerative colitis, 1 unclassified IBD) with a mean BMI of 41.6 ± 5.9 kg/m2. Bariatric surgery included Roux-en-Y gastric bypass (n = 3), sleeve gastrectomy (n = 73), and gastric banding (n = 12). Eight (9%) complications were reported, including 4 (5%) requiring surgery. At a mean follow-up of 34 months, mean weight was 88.6 ± 22.4 kg. No difference was observed between cases and controls for postoperative complications (P = .31), proportion of weight loss (P = .27), or postoperative deficiencies (P = .99). CONCLUSIONS: Bariatric surgery is a safe and effective procedure in patients with IBD and obesity; outcomes in this patient group were similar to those observed in a control population.

An Anti-migration Self-expandable and Removable Metal Stent for Crohn's Disease Strictures: A Nationwide Study From GETAID and SFED.

BACKGROUND AND AIMS: In Crohn's disease, strictures are frequent and may require surgical resection or endoscopic balloon dilation. An anti-migration, removable and shaped self-expandable metal stent is available. We evaluated its effectiveness and safety in a real-life setting. METHODS: All centres were asked to collect retrospectively or prospectively all data on patients who had a stent for a stricture. The anti-migration stent [Hanarostent HRC-20-080-230-MITech, Seoul, South Korea] was maintained 7 days before its extraction during a second colonoscopy. Short- and long-term efficacy and safety outcomes were evaluated. RESULTS: A total of 46 patients were enrolled. Strictures were anastomotic in 73.9% of cases. The median length of the stricture evaluated by cross-sectional imaging and during colonoscopy was 3.1 ± 1.7 and 2.7 ± 1.4 cm, respectively. Immediate success [no obstructive symptom at Day 30] was reported in 93.5% of cases (95% confidence interval [CI] = [86.3; 99.9]). Sixteen patients needed a new balloon dilation [n = 8] or surgery [n = 8]. The overall success rate [obstruction-free without any intervention] was 58.7% [n = 27] after a median follow-up of 26 months [8-41 months]. No perforation occurred and three migrations were observed [6.5%]. Perianal disease (hazard ratio [HR] = 0.1 [0.02; 0.58]) and discontinuation of an immunosuppressant (0.12 [0.02; 0.86]), were associated with a lower probability of success, whereas performing imaging (HR = 5.3 [1.2; 23.5]) before stent placement was associated with success. CONCLUSIONS: The anti-migration stent is safe and effective in about half of patients, with no perforation reported in this study, and has an extremely low migration rate.

Cost savings using a test-based de-escalation strategy for patients with Crohn's disease in remission on optimized infliximab: A discrete event model study.

BACKGROUND: Drug de-escalation is considered in Crohn's disease patients in sustained remission on optimized infliximab treatment. AIM: We built a model to evaluate the magnitude of cost savings in patients' disease course with or without drug de-escalation guided by infliximab trough levels. METHODS: We designed 4 virtual cohorts (P1-P4) of 10,000 patients in clinical remission on optimized infliximab treatment followed for 2 years. P1: no drug de-escalation - 10 mg/kg/8 weeks; P2: drug de-escalation from 10 mg/kg/8 weeks to 5 mg/kg/8 weeks according to trough levels; P3: no drug de-escalation - 10 mg/kg/6 weeks; and P4: drug de-escalation from 10 mg/kg/6 weeks to 10 mg/kg/8 weeks according to trough levels. For P2 and P4 cohorts, drug de-escalation was decided if trough levels were ≥7 µg/mL and no de-escalation if trough levels were <7 µg/mL. Only costs related to drug administration were considered. RESULTS: The cost differences when comparing P1 versus P2 and P3 versus P4 were 7.6% and 4.6%, respectively, corresponding to costs savings of €30.5 millions and €20.3 million for 10,000 patients. CONCLUSION: Over a 2-year period, infliximab de-escalation according to trough levels led to cost saving of about 6%, corresponding to around €25.4 million.

Cost-effectiveness of drug monitoring of anti-TNF therapy in inflammatory bowel disease and rheumatoid arthritis: a systematic review.

BACKGROUND: Therapeutic drug monitoring (TDM) of anti-TNF is increasingly used to manage inflammatory bowel diseases (IBD) and rheumatoid arthritis (RA). The cost-effectiveness of this strategy is debated. METHODS: All studies comparing the cost-effectiveness of a TDM-based strategy and an empirical dose management of anti-TNF in IBD or RA were screened. Studies were identified through the MEDLINE electronic database (up to July 2016), and annual international meeting abstracts were also manually reviewed. RESULTS: Seven studies were included: two randomized controlled trials (RCTs) enrolling 332 patients [247 Crohn's disease (CD) and 85 ulcerative colitis (UC)] and five modeling approaches. Four studies included only CD patients, one included both CD and UC patients, and two included only RA patients. Three studies compared the cost-effectiveness of the two strategies in patients with secondary infliximab (IFX) failure (dose-escalation strategy), one in patients in remission on optimized IFX (de-escalation strategy), one in patients starting adalimumab, and two in patients with clinical response to maintenance anti-TNF therapy. The two RCTs demonstrated that a TDM strategy led to major cost savings, ranging from 28 to 34 %. The three modeling approaches with regard to CD patients demonstrated cost savings ranging from $5396 over a 1-year period to €13,130 per patient at 5 years of follow-up. A TDM strategy also led to major cost savings in the two modeling approaches in RA patients. CONCLUSIONS: Available evidence indicates that a TDM strategy leads to major cost savings related to anti-TNF therapy in both IBD and RA patients, with no negative impact on efficacy.

Screening of esophageal varices by esophageal capsule endoscopy: results of a French multicenter prospective study.

BACKGROUND AND STUDY AIM: Esophageal video capsule endoscopy (ECE) is a new technique that allows examination of the esophagus using a noninvasive approach. The aim of this study was to compare ECE with esophagogastroduodenoscopy (EGD) for the diagnosis of esophageal varices in patients with cirrhosis. PATIENTS AND METHODS: A total of 330 patients with cirrhosis and with no known esophageal varices were prospectively enrolled. Patients underwent ECE first, followed by EGD (gold standard). The endoscopists who performed EGD were blind to the ECE result. Patient satisfaction was assessed using a visual analog scale (maximum score 100). RESULTS: A total of 30 patients were excluded from the analysis because they did not undergo any endoscopic examinations. Patients (mean age 56 years; 216 male) had mainly alcoholic (45 %) or viral (27 %) cirrhosis. The diagnostic indices of ECE to diagnose and correctly stage esophageal varices were: sensitivity 76 % and 64 %, specificity 91 % and 93 %, positive predictive value 88 % and 88 %, and negative predictive value 81 % and 78 %, respectively. ECE patient satisfaction scored significantly higher than EGD (87 ±â€Š22 vs. 58 ±â€Š35; P < 0.0001). CONCLUSIONS: ECE was well tolerated and safe in patients with liver cirrhosis and suspicion of portal hypertension. The sensitivity of ECE is not currently sufficient to replace EGD as a first exploration in these patients. However, due to its excellent specificity and positive predictive value, ECE may have a role in cases of refusal or contraindication to EGD. ECE might also improve compliance to endoscopic follow-up and aid important therapeutic decision making in the prophylaxis of bleeding. TRIAL REGISTRATION: EudraCT (ID RCB 2009-A00532-55) and ClinicalTrials.gov (NCT00941421).

Cost savings of anti-TNF therapy using a test-based strategy versus an empirical dose escalation in Crohn's disease patients who lose response to infliximab.

BACKGROUND: The use of pharmacokinetics is associated with cost savings in anti-tumor necrosis factor (anti-TNF) therapy, but the long-term cost savings in a large cohort of Crohn's disease (CD) patients are unknown. AIM: The goal of this study was to compare the cost of anti-TNF therapy in two cohorts of CD patients losing response to infliximab, one using a test-based strategy and one an empirical dose escalation. METHODS: We used a selected mathematical model to describe the trajectories of CD patients based on a discrete event system. This design allowed us to track over a given period a double cohort of patients who moved randomly and asynchronously from one state to another, while keeping all the information on their entire trajectory. Both cohorts were modeled using state diagram parameters where transition probabilities from one state to another are derived from literature data. Costs were estimated based on the French health care system. RESULTS: Cost savings among the 10,000 CD patients using a test-based strategy were €131,300,293 at 5 years. At 5 years the mean cost saving was €13,130 per patient. The direct cost of the test had no impact on the results until the cost per test reached €2,000. CONCLUSIONS: A test-based strategy leads to major cost savings related to anti-TNF therapy in CD.

Bevacizumab as rescue treatment for severe recurrent gastrointestinal bleeding in hereditary hemorrhagic telangiectasia.

Hereditary hemorrhagic telangiectasia (HHT) also known as Rendu Osler syndrome is a vascular hereditary autosomal dominant disease, leading to a dysfunction in the development of arteriovenous capillaries, usually resulting in epistaxis, gastrointestinal (GI) bleeding, and iron deficiency anemia. It is believed that by interfering and stopping angiogenesis, anti-vascular endothelial growth factor molecules could be an option for HHT patients. Indeed, an intranasal treatment regime of diluted Avastin (bevacizumab; recombinant humanized antivascular epithelial growth factor immunoglobin G1) has proven clinically efficacious in patients with HHT1. However, there are no data available regarding bevacizumab's effect in patients with HHT and GI bleeding. We report here the case of an 85-year-old woman, suffering from life-threatening GI bleeding due to HHT with an impressive clinical response using anti-vascular endothelial growth factor infusion.

Urgent endoscopy in severe non-variceal upper gastrointestinal hemorrhage: does the Glasgow-Blatchford score help endoscopists?

OBJECTIVE: The Glasgow-Blatchford score (GBS) has been validated to select severe patients with non-variceal upper gastrointestinal hemorrhage (UGIH). The aim was to compare the yield of the triage based on the GBS with an endoscopist' decision to perform an urgent upper gastrointestinal endoscopy (UGIE) in newly admitted patients and inpatients with UGIH in the setting of an endoscopy on-duty service in 13 tertiary care centers. MATERIAL AND METHODS: During a 6-month period, GBS and patient data were collected for all patients with non-variceal UGIH for whom an UGIE was requested in emergency. If patients experienced severe endoscopic lesion, surgery or death, they were categorized as patients who had been at need for urgent UGIE. RESULTS: The 102 UGIH patients included (mean age 62, men 73%) had a median GBS of 12 (range 0-21), significantly lower for new patients compared with inpatients (11, range 0-21 vs. 14, range 2-21, respectively, p = 0.001). If triage for urgent UGIE had followed the GBS, no more patients would have had an urgent UGIE compared with what endoscopists performed (99/102 (97%) vs. 92/102 (90%), respectively, p = 0.09). Sensitivity for the detection of patients who needed an UGIE was no different with the GBS than endoscopists (98% vs. 98%, respectively, p = 0.10) and both showed insufficient specificity (4% and 19%, respectively). CONCLUSIONS: The GBS does not detect more patients at need for urgent UGIE than on-duty endoscopists. Both methods lead to numerous unjustified UGIEs. A score that would equally help endoscopists in their decision to intervene urgently is still warranted.

Safety and efficacy of extractible self-expandable metal stents in the treatment of Crohn's disease intestinal strictures: a prospective pilot study.

BACKGROUND: Endoscopic management of Crohn's disease (CD) intestinal strictures with balloon dilation is effective; however, recurrences are frequent and require further dilations or surgery. The use of extractible metallic stents may be as effective as balloon dilation with fewer recurrences. The aim was to investigate in a prospective pilot study the feasibility and clinical effectiveness of the use of extractible stents in the treatment of CD intestinal strictures. METHODS: In two tertiary referral centers, quiescent CD patients except for obstructive symptoms associated with intestinal stenosis of less than 50 mm length on enterography were eligible for transitory stent placement, initially planned to be retrieved after 8 weeks, which was secondarily reduced to 4 weeks after patient 3. RESULTS: Eleven patients (six males, five females, median age 34 years [range 18-66]) were prospectively included. The sites of intestinal stenosis were an ileocolonic anastomosis, an ileosigmoidic anastomosis, and the surgically untreated terminal ileum in eight, one, and two patients, respectively. Stent placement was technically successful in 10 patients. Obstructive symptoms were relieved in 6 out of 10 patients. Two patients needed surgery related to the procedure. Six downstream migrations were observed. Only one patient could have the stent extracted as scheduled on day 28 and remains symptom-free after 73 months of follow-up. CONCLUSIONS: Even if stenting appears an effective technique in treating symptomatic CD intestinal strictures, the procedure is associated with a prohibitively high rate of spontaneous migrations and complications.

Which magnetic resonance imaging findings accurately evaluate inflammation in small bowel Crohn's disease? A retrospective comparison with surgical pathologic analysis.

BACKGROUND: The aim was to evaluate the value of magnetic resonance imaging (MRI) findings in Crohn's disease (CD) in correlation with pathological inflammatory score using surgical pathology analysis as a reference method. METHODS: CD patients who were to undergo bowel resection surgery underwent MR enterography before surgery. The CD pathological inflammatory score of the surgical specimens was classified into three grades: mild or nonactive CD, moderately active CD, and severely active CD; fibrosis was also classified into three grades: mild, moderate, and severe. Mural and extramural MRI findings were correlated with pathological inflammatory and fibrosis grades. RESULTS: Fifty-three consecutive patients were included retrospectively. The mean delay between MRI and surgery was 24 days (range 1-90, median 14). The CD pathological inflammatory score was graded as follows: grade 0 (11 patients, 21%), grade 1 (15 patients, 28%), and grade 2 (27 patients, 51%). MRI findings significantly associated with pathological inflammatory grading were wall thickness (P < 0.0001), degree of wall enhancement on delayed phase (P < 0.0001), pattern of enhancement on both parenchymatous (P = 0.02), and delayed phase, (P = 0.008), T2 relative hypersignal wall (P < 0.0001), blurred wall enhancement (P = 0.018), comb sign (P = 0.004), fistula (P < 0.0001), and abscess (P = 0.049). The inflammation score correlated with the fibrosis score (r = 0.63, P = 0.0001). CONCLUSIONS: Our study identified MRI findings significantly associated with surgical pathological inflammation. These lesions are considered potentially reversible and may be efficiently treated medically. We also showed that fibrosis was closely and positively related to inflammation.

Nutritional status affects treatment tolerability and survival in metastatic colorectal cancer patients: results of an AGEO prospective multicenter study.

BACKGROUND: The possible impact of malnutrition on the tolerability and efficacy of modern chemotherapy regimens for metastatic colorectal cancer (mCRC) is unclear. METHODS: In this prospective, cross-sectional, multicenter study, we collected demographic, oncological and nutritional data for all consecutive mCRC patients during a 14-day period in eight hospitals. Nutritional status was assessed with the nutritional risk index (NRI), and patients were classified as severely malnourished when NRI was <83.5; drug-induced toxicities were evaluated using the National Cancer Institute Common Toxicity Criteria (version 3.0). Survival times were calculated from the date of the nutritional assessment. RESULTS: We enrolled 114 mCRC patients (median age: 65 years, range: 22-92; WHO performance status 0/1/2/3: 21/54/21/4%) of whom 88% had at least 2 metastatic sites and 49% were receiving chemotherapy as first-line treatment. Malnutrition was diagnosed in 65% of the patients and was severe in 19%. Severe malnutrition was associated with more adverse effects following chemotherapy (p = 0.01) and with shorter median overall survival (14.0 vs. 36.2 months in non-/moderately malnourished patients, p = 0.02). CONCLUSIONS: In mCRC patients, severe malnutrition is associated with greater chemotherapy toxicity and reduced overall survival.

Four-week short chain fructo-oligosaccharides ingestion leads to increasing fecal bifidobacteria and cholesterol excretion in healthy elderly volunteers.

BACKGROUND: Short-chain fructo-oligosaccharides (scFOS) are increasingly used in human diet for their prebiotic properties. We aimed at investigating the effects of scFOS ingestion on the colonic microflora and oro-fecal transit time in elderly healthy humans. METHODS: Stools composition, oro-fecal transit time, and clinical tolerance were evaluated in 12 healthy volunteers, aged 69 +/- 2 yrs, in three consecutive periods: basal period (2 weeks), scFOS (Actilight) ingestion period (8 g/d for 4 weeks) and follow-up period (4 weeks). Two-way ANOVA, with time and treatment as factors, was used to compare the main outcome measures between the three periods. RESULTS: Fecal bifidobacteria counts were significantly increased during the scFOS period (9.17 +/- 0.17 log cfu/g vs 8.52 +/- 0.26 log cfu/g during the basal period) and returned to their initial values at the end of follow-up (8.37 +/- 0.21 log cfu/g; P < 0.05). Fecal cholesterol concentration increased during the scFOS period (8.18 +/- 2.37 mg/g dry matter vs 2.81 +/- 0.94 mg/g dry matter during the basal period) and returned to the baseline value at the end of follow-up (2.87 +/- 0.44 mg/g dry matter; P < 0.05). Fecal pH tended to decrease during scFOS ingestion and follow-up periods compared to the basal period (P = 0.06). Fecal bile acids, stool weight, water percentage, and oro-fecal transit time did not change throughout the study. Excess flatus and bloating were significantly more frequent during scFOS ingestion when compared to the basal period (P < 0.05), but the intensity of these symptoms was very mild. CONCLUSION: Four-week 8 g/d scFOS ingestion is well tolerated and leads to a significant increase in fecal bifidobacteria in healthy elderly subjects. Whether the change in cholesterol metabolism found in our study could exert a beneficial action warrants further studies.

Incidence, risk factors, and complications of cholelithiasis in patients with home parenteral nutrition.

BACKGROUND: Previous studies showed high prevalence rates of cholelithiasis in patients with home parenteral nutrition (HPN). Our aim was to determine, in an HPN population, the incidence and risk factors for gallstones and sludge and their complications. STUDY DESIGN: Retrospective chart review was conducted in a tertiary care center. One hundred fifty-three consecutive patients who received HPN for longer than 2 months (range 2 to 204 months; median 15 months) between 1985 and 1997 were followed with ultrasonography. Kaplan-Meier curves and log-rank tests were calculated to assess risk factors for gallbladder lithiasis and complications. RESULTS: Thirty-four patients (22%) underwent cholecystectomy before HPN. Of the 119 remaining patients with gallbladder in situ, cholelithiasis appeared during HPN in 45 (38%). The probability of cholelithiasis developing during HPN was estimated to be 6.2%, 21.2%, and 38.7% at 6, 12, and 24 months, respectively. Biliary complications developed in eight patients (7%) during followup. Therapy consisted of endoscopic sphincterotomy (three patients) or operation (five patients) with uncomplicated outcomes except for one patient; no death was observed. Incidence rates of biliary complication during HPN were estimated to be 0.0%, 4.7%, and 10.1% at 6, 12, and 24 months, respectively. Nil or negligible ingesta was the only factor notably associated with incidence of cholelithiasis (p < 0.01) or biliary complications (p < 0.01). CONCLUSIONS: This first incidence study shows a high rate of cholelithiasis and a low rate of complications during HPN. Both events were notably related to nil or negligible ingesta.

Herpes simplex virus type 1 colitis in a patient with common variable immunodeficiency syndrome.

We report on a case of herpes simplex virus (HSV) type 1 colitis in a 69-year-old patient with common variable immunodeficiency syndrome. A treatment with polyvalent immunoglobulins was discontinued in April 2001. In March 2004 she developed chronic diarrhoea related to rectosigmoidal and caecal ulcerations. In November 2004, HSV was recovered in tissue culture from colonic biopsies. Valaciclovir was then started, leading the patient to clinical remission at day 4, and continued for a 6-week course (without any secondary antiviral prophylaxis). Colonic biopsies were negative for HSV by tissue culture and PCR within 3 weeks of antiviral treatment. Intravenous polyvalent immunoglobulin infusions were readministered within the third week of antiviral treatment. She has declared no clinical event since this period. Three months after the antiviral treatment was achieved, a rectosigmoidoscopy showed an ad-integrum macroscopic and histological mucosal healing whereas PCR was negative for HSV in the colonic tissue. As a large proportion of patients with common variable immunodeficiency syndrome present not only as a humoral immunodeficiency but also as a defect in the cellular immunity compartment (with T-cell deficits), HSV, as well as cytomegalovirus, should be investigated in patients with common variable immunodeficiency syndrome presenting colitis.