-
1.
Thiopurine Therapy for Inflammatory Bowel Disease During Pregnancy Is Not Associated with Anemia in the Infant.
Koslowsky, B, Sadeh, C, Grisaru-Granovsky, S, Miskin, H, Goldin, E, Bar-Gil Shitrit, A
Digestive diseases and sciences. 2019;(8):2286-2290
Abstract
INTRODUCTION Thiopurine exposure throughout pregnancy in patients with inflammatory bowel diseases (IBD) is common and teratogenically safe. Late consequences of in utero exposure to thiopurines and its metabolite, 6-thioguanine nucleotides (6-TGN), such as neonatal and infant anemia are still disputed. AIM: To evaluate whether 6-TGN exposure during pregnancy influences anemia in infants at 1 year of life. METHODS A comparative observational study was performed between 2009 and 2015 at a multidisciplinary IBD clinic dedicated to pregnant women. The hemoglobin level and signs of anemia between 9 and 15 months after birth of infants born to women exposed to thiopurines throughout the entire pregnancy was compared to infants of women with no thiopurine exposure during pregnancy. RESULTS Altogether, 34 patients, 21 in the study group and 13 in the control group, were included. The median duration of maternal thiopurine exposure prior to pregnancy was 24 months (range 12-72 months), and median dosage was 100 mg (range 50-175 mg). Maternal IBD activity, infants' iron supplementation, and iron deficiency diagnoses were similar between both groups. The infants' mean hemoglobin level (gr/dL) in the thiopurine-exposed women versus the control group was 11.48 ± 0.8 versus 11.54 ± 0.6, respectively, p = 0.81. The composite risk of any sign of infant anemia was numerically higher in the thiopurine-exposed women, 10 (47%), compared to non-exposed women, 3 (23%), p = 0.17. The mean corpuscular volume, red cell distribution width, white blood cell, and platelet counts were similar among groups. CONCLUSIONS Thiopurine therapy during pregnancy in women with IBD is safe for long-term neonatal outcomes; still large-scale confirmatory studies are required.
-
2.
Efficacy of Home Telemonitoring versus Conventional Follow-up: A Randomized Controlled Trial among Teenagers with Inflammatory Bowel Disease.
Heida, A, Dijkstra, A, Muller Kobold, A, Rossen, JW, Kindermann, A, Kokke, F, de Meij, T, Norbruis, O, Weersma, RK, Wessels, M, et al
Journal of Crohn's & colitis. 2018;(4):432-441
Abstract
BACKGROUND AND AIMS Conventional follow-up of teenagers with inflammatory bowel diseases [IBD] is done during scheduled outpatient visits regardless of how well the patient feels. We designed a telemonitoring strategy for early recognition of flares and compared its efficacy with conventional follow-up. METHODS We used a multicentre randomized trial in patients aged 10-19 years with IBD in clinical remission at baseline. Participants assigned to telemonitoring received automated alerts to complete a symptom score and send a stool sample for measurement of calprotectin. This resulted in an individual prediction for flare with associated treatment advice and test interval. In conventional follow-up the health check interval was left to the physician's discretion. The primary endpoint was cumulative incidence of disease flares. Secondary endpoints were percentage of participants with a positive change in quality-of-life and cost-effectiveness of the intervention. RESULTS We included 170 participants [84 telemonitoring; 86 conventional follow-up]. At 52 weeks the mean number of face-to-face visits was significantly lower in the telemonitoring group compared to conventional follow-up [3.6 vs 4.3, p < 0.001]. The incidence of flares [33 vs 34%, p = 0.93] and the proportion of participants reporting positive change in quality-of-life [54 vs 44%, p = 0.27] were similar. Mean annual cost-saving was €89 and increased to €360 in those compliant to the protocol. CONCLUSIONS Telemonitoring is as safe as conventional follow-up, and reduces outpatient visits and societal costs. The positive impact on quality-of-life was similar in the two groups. This strategy is attractive for teenagers and families, and health professionals may be interested in using it to keep teenagers who are well out of hospital and ease pressure on overstretched outpatient services. TRIAL REGISTRATION NTR3759 [Netherlands Trial Registry].
-
3.
Intravenous Versus Oral Iron for the Treatment of Anemia in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Bonovas, S, Fiorino, G, Allocca, M, Lytras, T, Tsantes, A, Peyrin-Biroulet, L, Danese, S
Medicine. 2016;(2):e2308
-
-
Free full text
-
Abstract
Anemia is the most prevalent extraintestinal complication of inflammatory bowel disease (IBD). Our aim was to evaluate the comparative efficacy and harm of intravenous (IV) versus oral iron supplementation for correcting anemia in adult IBD patients.We conducted a systematic review and meta-analysis to integrate evidence from randomized controlled trials having enrolled adults with IBD, and comparing IV versus oral iron (head-to-head) for correcting iron-deficiency anemia. Medline, Embase, Scopus, and the Web of Science database were searched through July 2015. The Cochrane Central Register of Controlled Trials, the WHO International Clinical Trials Registry Platform, the ClinicalTrials.gov, and international conference proceedings were also investigated. Two reviewers independently abstracted study data and outcomes, and rated each trial's risk-of-bias. Pooled odds ratio (OR) estimates with their 95% CIs were calculated using fixed- and random-effects models.Five eligible studies, including 694 IBD patients, were identified. In meta-analysis, IV iron demonstrated a higher efficacy in achieving a hemoglobin rise of ≥2.0 g/dL as compared to oral iron (OR: 1.57, 95% CI: 1.13, 2.18). Treatment discontinuation rates, due to adverse events or intolerance, were lower in the IV iron groups (OR: 0.27, 95% CI: 0.13, 0.59). Similarly, the occurrence of gastrointestinal adverse events was consistently lower in the IV iron groups. On the contrary, serious adverse events (SAEs) were more frequently reported among patients receiving IV iron preparations (OR: 4.57, 95% CI: 1.11, 18.8); however, the majority of the reported SAEs were judged as unrelated or unlikely to be related to the study medication. We found no evidence of publication bias, or between-study heterogeneity, across all analyses. Risk of bias was high across primary studies, because patients and personnel were not blinded to the intervention.IV iron appears to be more effective and better tolerated than oral iron for the treatment of IBD-associated anemia.
-
4.
Water-Aided Colonoscopy in Inflammatory Bowel Disease Patients-A Randomised, Single-Centre Trial.
Falt, P, Šmajstrla, V, Fojtík, P, Urban, O, Hill, M
Journal of Crohn's & colitis. 2015;(9):720-4
Abstract
BACKGROUND Water-aided colonoscope insertion reduces patients' discomfort and need for sedation in unsedated and minimally sedated patients. However, water-aided technique has never been studied in inflammatory bowel disease patients, characterised by younger age, structural changes of the colon and need for repeated colonoscopies. Our trial was designed to evaluate discomfort associated with water-aided colonoscopy compared with air insufflation in on-demand sedated patients with known inflammatory bowel disease. METHODS In a randomised, single-centre study, 92 patients were randomised to either water-aided insertion and air insufflation during withdrawal [Water] or air insufflation during both insertion and withdrawal [Air]. The main outcome measured was success rate of unsedated colonoscopy, defined as reaching the caecum without requiring sedation and with discomfort during insertion of less than or equal to 5 using 0-10 continuous scale [0 = none, 10 = maximum pain]. RESULTS Success rate of caecal intubation without sedation or invoking a discomfort score greater than 5 was significantly higher in the Water arm compared with the Air arm [73.9 vs 45.7%, p = 0.01]. Discomfort score during insertion [mean ± SD] was significantly lower in the Water than in the Air arm [3.8±2.4 vs 5.4±1.9, p < 0.001]. Other outcomes including procedural times, success rate of terminal ileum intubation, need for abdominal compression, and repositioning were comparable. There were no complications recorded in the study. CONCLUSIONS Compared with air insufflation, water-aided colonoscopy significantly reduces discomfort in on-demand sedated patients with inflammatory bowel disease, achieving comparable procedural outcomes.
-
5.
Consensus statements on the risk, prevention, and treatment of venous thromboembolism in inflammatory bowel disease: Canadian Association of Gastroenterology.
Nguyen, GC, Bernstein, CN, Bitton, A, Chan, AK, Griffiths, AM, Leontiadis, GI, Geerts, W, Bressler, B, Butzner, JD, Carrier, M, et al
Gastroenterology. 2014;(3):835-848.e6
Abstract
BACKGROUND & AIMS Guidelines for the management of venous thromboembolism (VTE) from the American College of Chest Physicians do not address patients with inflammatory bowel disease (IBD), a group with a high risk of both VTE and gastrointestinal bleeding. We present recommendations for the prevention and treatment of VTE in patients with IBD. METHODS A systematic literature search was performed to identify studies on VTE in IBD. The quality of evidence and strength of recommendations were rated according to the Grading of Recommendation Assessment, Development, and Evaluation (GRADE) approach. Statements were developed through an iterative online platform, then finalized and voted on by a working group of adult and pediatric gastroenterologists and thrombosis specialists. RESULTS IBD patients have an approximately 3-fold higher risk of VTE compared with individuals without IBD, and disease flares further increase this risk. Anticoagulant thromboprophylaxis is recommended for IBD patients who are hospitalized with IBD flares without active bleeding and is suggested when bleeding is nonsevere. Anticoagulant thromboprophylaxis is suggested during moderate-severe IBD flares in outpatients with a history of VTE provoked by an IBD flare or an unprovoked VTE, but not otherwise. The recommended duration of anticoagulation after a first VTE is based on the presence of provoking factors. Specific suggestions are made for the prevention and treatment of VTE in pediatric and pregnant IBD patients. CONCLUSIONS Using the American College of Chest Physicians' guidelines as a foundation, we have integrated evidence from IBD studies to develop specific recommendations for the management of VTE in this high-risk population.
-
6.
Diagnostic performance of 18F-FDG-PET versus scintigraphy in patients with inflammatory bowel disease: a meta-analysis of prospective literature.
Zhang, J, Li, LF, Zhu, YJ, Qiu, H, Xu, Q, Yang, J, Weng, WW, Liu, NH
Nuclear medicine communications. 2014;(12):1233-46
Abstract
OBJECTIVE The aim of this study was to evaluate the diagnostic performance of fluorine-18 fluorodeoxyglucose-PET (F-FDG-PET), leukocyte scintigraphy (LS), and monoclonal antigranulocyte antibody scintigraphy (MAAS) in patients with inflammatory bowel disease (IBD) and perform pairwise comparisons of the diagnostic accuracy between these different imaging modalities. METHODS Through a search of PubMed, EMBASE, and the Cochrane Library (January 1993-May 2013), we performed a random effects meta-analysis and constructed summary receiver operating characteristic curves on per-bowel-segment or per-patient basis. Two-sample Z-tests were performed to evaluate differences in sensitivity, specificity, area under the curve (AUC), and the Q* index between any two diagnostic modalities on per-bowel-segment basis. RESULTS Twenty prospective studies were reviewed. On per-bowel-segment basis, the F-FDG-PET had a pooled sensitivity of 0.84, specificity of 0.86, AUC of 0.913, and Q* index of 0.845, whereas for LS, the corresponding values were 0.79, 0.86, 0.877, and 0.808, respectively, and for MAAS they were 0.45, 0.94, 0.524, and 0.518, respectively. On per-patient basis, the corresponding values of LS were 0.91, 0.85, 0.937, and 0.874, respectively. Statistically significant differences were not found in the sensitivity, specificity, AUC, and Q* index between F-FDG-PET and LS on per-bowel-segment basis. CONCLUSION F-FDG-PET has a high degree of diagnostic performance compared with LS and MAAS on per-bowel-segment basis in patients with IBD. LS may be used with satisfactory diagnostic accuracy in detecting active IBD when PET systems are unavailable. A larger prospective validation of these findings would be valuable.
-
7.
Comparing guidelines for the treatment of inflammatory bowel disease.
Hanauer, SB, Kirsner, JB
Digestive diseases (Basel, Switzerland). 2013;(3-4):360-2
Abstract
As we enter into the era of 'personalized medicine', many of the recommendations of 'evidence-based medicine' require scrutiny and adaptation to optimize individual outcomes. Several examples of these discrepancies are exemplified by the topics of aminosalicylate use in Crohn's disease, early use of biologic agents that target TNF and the role of calcineurin inhibitors versus anti-TNF agents in steroid-refractory ulcerative colitis.
-
8.
A randomized, open-label, non-inferiority study of intravenous iron isomaltoside 1,000 (Monofer) compared with oral iron for treatment of anemia in IBD (PROCEED).
Reinisch, W, Staun, M, Tandon, RK, Altorjay, I, Thillainayagam, AV, Gratzer, C, Nijhawan, S, Thomsen, LL
The American journal of gastroenterology. 2013;(12):1877-88
-
-
Free full text
-
Abstract
OBJECTIVES In the largest head-to-head comparison between an oral and an intravenous (IV) iron compound in patients with inflammatory bowel disease (IBD) so far, we strived to determine whether IV iron isomaltoside 1,000 is non-inferior to oral iron sulfate in the treatment of iron deficiency anemia (IDA). METHODS This prospective, randomized, comparative, open-label, non-inferiority study was conducted at 36 sites in Europe and India. Patients with known intolerance to oral iron were excluded. A total of 338 IBD patients in clinical remission or with mild disease, a hemoglobin (Hb) <12 g/dl, and a transferrin saturation (TSAT) <20% were randomized 2:1 to receive either IV iron isomaltoside 1,000 according to the Ganzoni formula (225 patients) or oral iron sulfate 200 mg daily (equivalent to 200 mg elemental iron; 113 patients). An interactive web response system method was used to randomize the eligible patient to the treatment groups. The primary end point was change in Hb from baseline to week 8. Iron isomaltoside 1,000 and iron sulfate was compared by a non-inferiority assessment with a margin of -0.5 g/dl. The secondary end points, which tested for superiority, included change in Hb from baseline to weeks 2 and 4, change in s-ferritin, and TSAT to week 8, number of patients who discontinued study because of lack of response or intolerance of investigational drugs, change in total quality of life (QoL) score to weeks 4 and 8, and safety. Exploratory analyses included a responder analysis (proportion of patients with an increase in Hb ≥2 g/dl after 8 weeks), the effect of regional differences and total iron dose level, and other potential predictors of the treatment response. RESULTS Non-inferiority in change of Hb to week 8 could not be demonstrated. There was a trend for oral iron sulfate being more effective in increasing Hb than iron isomaltoside 1,000. The estimated treatment effect was -0.37 (95% confidence interval (CI): -0.80, 0.06) with P=0.09 in the full analysis set (N=327) and -0.45 (95% CI: -0.88, -0.03) with P=0.04 in the per protocol analysis set (N=299). In patients treated with IV iron isomaltoside 1,000, the mean change in s-ferritin concentration was higher with an estimated treatment effect of 48.7 (95% CI: 18.6, 78.8) with P=0.002, whereas the mean change in TSAT was lower with an estimated treatment effect of -4.4 (95% CI: -7.4, -1.4) with P=0.005, compared with patients treated with oral iron. No differences in changes of QoL were observed. The safety profile was similar between the groups. The proportion of responders with Hb ≥2 g/dl (IV group: 67%; oral group: 61%) were comparable between the groups (P=0.32). Iron isomaltoside 1,000 was more efficacious with higher cumulative doses of >1,000 mg IV. Significant predictors of Hb response to IV iron treatment were baseline Hb and C-reactive protein (CRP). CONCLUSIONS We could not demonstrate non-inferiority of IV iron isomaltoside 1,000 compared with oral iron in this study. Based on the dose-response relationship observed with the IV iron compound, we suggest that the true iron demand of IV iron was underestimated by the Ganzoni formula in our study. Alternative calculations including Hb and CRP should be explored to gauge iron stores in patients with IBD.
-
9.
Is pediatric IBD treatment different than in adults?
Lev-Tzion, R, Turner, D
Minerva gastroenterologica e dietologica. 2012;(2):137-50
Abstract
The incidence of pediatric inflammatory bowel disease (IBD) continues to rise in most countries. Approximately 20-25% of IBD patients present before the age of 20, and their management is associated with many unique challenges. These challenges stem both from the inherent differences between children and adults, and from the differences in the nature and course of the disease. Children with IBD are more likely than adults to present with extensive disease ‑ both in Crohn's disease (CD) and ulcerative colitis (UC). Diagnosis requires a high index of suspicion, as children may present with less typical signs such as poor growth and delayed puberty. In the very young patients with inflammatory bowel disease, the pediatric clinician must consider a broader range of immunological and allergic disorders. Optimal management requires recognition of pediatric patterns of presentation, efficacy and adverse-effect profiles, and understanding monitoring aspects unique to pediatrics. These aspects include pediatric disease-related psychological issues, adherence to therapy and transition to adult care. Inadequate attention to growth, puberty or bone health in childhood can result in long-term consequences, such as impaired adult height and increased risk of fractures. Management of pediatric IBD and prevention of adverse long-term consequences relies on a variety of therapies well-known to the adult practitioner, along with therapies that are not widespread in adults, most notably exclusive enteral nutrition (EEN). The latter is as effective as corticosteroids in achieving clinical remission in children, while achieving better results than corticosteroids with regard to mucosal healing and growth. This review discusses the broad variety of issues that form the basis for management of pediatric IBD.
-
10.
Treatment of vitamin D insufficiency in children and adolescents with inflammatory bowel disease: a randomized clinical trial comparing three regimens.
Pappa, HM, Mitchell, PD, Jiang, H, Kassiff, S, Filip-Dhima, R, DiFabio, D, Quinn, N, Lawton, RC, Varvaris, M, Van Straaten, S, et al
The Journal of clinical endocrinology and metabolism. 2012;(6):2134-42
-
-
Free full text
-
Abstract
CONTEXT Vitamin D insufficiency [serum 25-hydroxyvitamin D (25OHD) concentration less than 20 ng/ml] is prevalent among children with inflammatory bowel disease (IBD), and its treatment has not been studied. OBJECTIVE The aim of this study was to compare the efficacy and safety of three vitamin D repletion regimens. DESIGN AND SETTING We conducted a randomized, controlled clinical trial from November 2007 to June 2010 at the Clinical and Translational Study Unit of Children's Hospital Boston. The study was not blinded to participants and investigators. PATIENTS Eligibility criteria included diagnosis of IBD, age 5-21, and serum 25OHD concentration below 20 ng/ml. Seventy-one patients enrolled, 61 completed the trial, and two withdrew due to adverse events. INTERVENTION Patients received orally for 6 wk: vitamin D(2), 2,000 IU daily (arm A, control); vitamin D(3), 2,000 IU daily (arm B); vitamin D(2), 50,000 IU weekly (arm C); and an age-appropriate calcium supplement. MAIN OUTCOME MEASURE We measured the change in serum 25OHD concentration (Δ25OHD) (ng/ml). Secondary outcomes included change in serum intact PTH concentration (ΔPTH) (pg/ml) and the adverse event occurrence rate. RESULTS After 6 wk, Δ25OHD ± se was: 9.3 ± 1.8 (arm A); 16.4 ± 2.0 (arm B); 25.4 ± 2.5 (arm C); P (A vs. C) = 0.0004; P (A vs. B) = 0.03. ΔPTH ± SE was -5.6 ± 5.5 (arm A); -0.1 ± 4.2 (arm B); -4.4 ± 3.9 (arm C); P = 0.57. No participant experienced hypercalcemia or hyperphosphatemia, and the prevalence of hypercalciuria did not differ among arms at follow-up. CONCLUSIONS Oral doses of 2,000 IU vitamin D(3) daily and 50,000 IU vitamin D(2) weekly for 6 wk are superior to 2,000 IU vitamin D(2) daily for 6 wk in raising serum 25OHD concentration and are well-tolerated among children and adolescents with IBD. The change in serum PTH concentration did not differ among arms.