Weight-Loss Endoscopy Trial: A Multicenter, Randomized, Controlled Trial Comparing Weight Loss in Endoscopically Implanted Duodenal-Jejunal Bypass Liners versus Intragastric Balloons versus a Sham Procedure.

INTRODUCTION: Obesity is associated with reduced life expectancy and various comorbidities. Surgical interventions are effective but accompanied by the risk of serious complications. Less invasive endoscopic procedures mainly comprise the intragastric balloon (IB) and the duodenal-jejunal bypass liner (DJBL). A randomized, sham-controlled study comparing both procedures has not been undertaken so far. METHODS: We performed a randomized, patient- and assessor-blinded, controlled trial comparing weight loss in IB versus DJBL versus a sham procedure (2:2:1 ratio). Patients with a BMI >35 kg/m2 or >30 with obesity-related comorbidities were included. The IB was removed after 6 months and the DJBL after 12 months. The main objective was successful weight loss (>10% from baseline) 12 months after explantation of the devices. Secondary outcomes were changes in comorbidities, quality of life, and complications. RESULTS: Thirty-three patients were randomized. Recruitment has to be stopped suddenly in after the DJBL device lost its CE mark in Europe. In all, 11 patients received DJBL, 15 IB, and 7 were allocated to the sham group. Blinding was feasible in all patients. Weight decreased from baseline until explantation (DJBL: 129.4 ± 28.3 kg to 107.4 ± 16.7 kg; IB: 118.3 ± 22.8 kg to 107.4 ± 25.7 kg; sham: 134.6 ± 18.0 kg to 131.2 ± 14.3 kg), but patients regained weight almost to the baseline level 12 months after explantation. Only 1 patient in IB group reached the primary endpoint. Severe device-related complications were very rare. CONCLUSION: Endoscopic bariatric procedures failed to achieve effective weight loss 12 months after explantation of the devices. The results of this trial need to be interpreted with caution due to its early termination.

Glycemic control and BMI changes after endoscopic implantation of a duodenojejunal bypass liner compared with laparoscopic Roux-en-Y gastric bypass surgery: a propensity score matching analysis.

INTRODUCTION: Both laparoscopic Roux-en-Y gastric bypass (RYGB) and duodenojejunal bypass liner (DJBL) have been shown to induce weight loss and dramatically ameliorate type 2 diabetes mellitus (T2DM). Since DJBL implantation causes nutrients to pass through the duodenum without contact with the digestive juices and the duodenal mucosa, its mechanisms have been suggested to mimic those of RYGB. This study aimed to compare the outcomes of these two bariatric procedures in terms of glycemic control and BMI in patients with obesity and T2DM. RESEARCH DESIGN AND METHODS: A retrospective observational cohort propensity score-weighted comparison of laparoscopic Roux-en-Y gastric bypass (RYGB) vs duodenojejunal bypass liner (DJBL) was conducted in patients with obesity and T2DM undergoing either procedure from 05/2014 to 12/2017. Propensity scores were weighted for body weight, body mass index (BMI), and glycated hemoglobin A1c (HbA1c). The primary outcome was comparative improvement of HbA1c. Secondary comparative effectiveness outcomes were decrease of body weight and BMI. RESULTS: Forty-six patients were included: 21 (10 male, 11 female; mean age 50.6 ± 11.7 years) underwent RYGB, while DJBL was implanted in 25 (10 male, 15 female; 52.5 ± 9.5 years). After twelve months, mean ΔBMI was 11.54 ± 4.47 kg/m2 for RYGB vs. 6.23 ± 2.36 kg/m2 for DJBL (p < 0.05). Mean total weight loss was 27.93 ± 8.57% for RYGB vs. 15.04 ± 5.73% for DJBL (p < 0.05). Glycemic control after one year improved significantly in both groups but did not differ significantly. CONCLUSION: RYGB and DJBL seem to be associated with similar remission rates of hyperglycemia after one year. However, RYGB induces more significant weight loss than DJBL.

Tetramodal therapy with transurethral resection followed by chemoradiation in combination with hyperthermia for muscle-invasive bladder cancer: early results of a multicenter phase IIB study.

BACKGROUND: Transurethral resection of bladder tumor (TUR-BT) followed by chemoradiation (CRT) is a valid treatment option for patients with muscle-invasive bladder cancer (MIBC). This study aimed to investigate the efficacy of a tetramodal approach with additional regional hyperthermia (RHT). METHODS: Patients with stages T2-4 MIBC were recruited at two institutions. Treatment consisted of TUR-BT followed by radiotherapy at doses of 57-58.2 Gy with concurrent weekly platinum-based chemotherapy and weekly deep RHT (41-43 °C, 60 min) within two hours of radiotherapy. The primary endpoint was a complete response six weeks after the end of treatment. Further endpoints were cystectomy-free rate, progression-free survival (PFS), local recurrence-free survival (LRFS), overall survival (OS) and toxicity. Quality of life (QoL) was assessed at follow-up using the EORTC-QLQ-C30 and QLQ-BM30 questionnaires. Due to slow accrual, an interim analysis was performed after the first stage of the two-stage design. RESULTS: Altogether 27 patients were included in the first stage, of these 21 patients with a median age of 73 years were assessable. The complete response rate of evaluable patients six weeks after therapy was 93%. The 2-year cystectomy-free rate, PFS, LRFS and OS rates were 95%, 76%, 81% and 86%, respectively. Tetramodal treatment was well tolerated with acute and late G3-4 toxicities of 10% and 13%, respectively, and a tendency to improve symptom-related quality of life (QoL) one year after therapy. CONCLUSION: Tetramodal therapy of T2-T4 MIBC is promising with excellent local response, moderate toxicity and good QoL. This study deserves continuation into the second stage.

Intravenous ferric carboxymaltose for the management of iron deficiency and iron deficiency anaemia in children and adolescents: a review.

Iron deficiency is the primary cause of anaemia worldwide and is particularly common among children and adolescents. Intravenous (IV) iron therapy is recommended for paediatric patients with certain comorbidities or if oral iron treatment has been unsuccessful. IV ferric carboxymaltose (FCM) has recently been approved by the US Food and Drug Administration for use in children aged > 1 year. This narrative review provides an overview of the available publications on the efficacy and safety of IV FCM in children and adolescents. A literature search using PubMed and Embase yielded 153 publications; 33 contained clinical data or reports on clinical experience relating to IV FCM in subjects < 18 years of age and were included in the review. No prospective, randomised controlled studies on the topic were found. Most publications were retrospective studies or case reports and included patients with various underlying conditions or patients with inflammatory bowel disease. Efficacy data were included in 27/33 publications and improvements in anaemia, and/or iron status parameters were reported in 26 of them. Safety data were included in 25/33 publications and were in line with the adverse events described in the prescribing information. CONCLUSION: The available publications indicate that IV FCM, a nanomedicine with a unique and distinctive therapeutic profile, is an effective and generally well-tolerated treatment for iron deficiency or iron deficiency anaemia in children and adolescents. Despite the wealth of retrospective evidence, prospective, randomised controlled trials in the paediatric setting are still necessary. WHAT IS KNOWN: • Iron deficiency and iron deficiency anaemia are usually managed using oral iron therapy, but intravenous iron therapy is recommended for certain paediatric patients. • Intravenous ferric carboxymaltose (FCM) has recently been approved in the US for use in children aged > 1 year. WHAT IS NEW: • Despite evidence that FCM is effective and generally well tolerated in children and adolescents, so far, only retrospective studies, non-randomised uncontrolled prospective studies, or case reports have been published in full. • There is a strong need for prospective, randomised controlled trials on FCM in the paediatric setting.

Serum Hepcidin Levels Predict Intestinal Iron Absorption in Patients with Inflammatory Bowel Disease.

BACKGROUND: Hepcidin has been shown to be inversely associated with iron absorption and the expression of iron transport proteins in healthy females and patients with iron deficiency. Data describing the relationship between hepcidin expression and iron absorption in patients with inflammatory bowel disease (IBD) are lacking. The objective of this study was to assess the relationship between serum concentrations of hepcidin and iron absorption in patients with IBD and iron deficiency by means of an oral iron absorption test. METHODS: This study was conducted as a comparative, single-centered, open clinical trial. After overnight fasting, an oral iron absorption test was performed, serum iron concentrations were measured 60, 90, 120, 180, and 240 minutes. Changes in iron levels between baseline and the 2-hour timepoint were calculated and recorded. RESULTS: Both ferritin and serum hepcidin levels are found to be good predictors of iron malabsorption, with sensitivity and specificity both at levels > 95%. When the two markers are compared, in our analysis, serum hepcidin levels (AUC: 0.817) tended to predict iron malabsorption slightly better than serum ferritin (AUC: 0.788). CONCLUSIONS: The evidence from our study suggests that serum hepcidin levels are a promising predictor of absorptive capacity in patients treated with oral iron compounds.

Safety and efficacy of intravenous iron isomaltoside for correction of anaemia in patients with inflammatory bowel disease in everyday clinical practice.

AIMS: Iron deficiency anaemia (IDA) is common in patients with inflammatory bowel disease (IBD), who are often treated with intravenous iron. This observational study aimed to investigate the effectiveness and safety of iron isomaltoside in routine practical care of IDA in IBD patients. METHODS: The study included 197 IBD patients designated for treatment with iron isomaltoside. Treatment was administered according to routine practice. Data were recorded at baseline and after approximately 4, 8, and 16 weeks. Efficacy data included haemoglobin (Hb) levels and haematinics, while safety data included adverse drug reactions and safety laboratory variables. RESULTS: Patients received a mean (range) cumulative dose of 1304 (100-3500) mg iron isomaltoside. Hb increased from 10.7(±1.6) g/dL at baseline to 13.1(±1.5) g/dL at the final visit. In addition, serum iron, ferritin and transferrin saturation increased and soluble transferrin receptor decreased. Calprotectin decreased, as did IBD symptom scores, Harvey-Bradshaw Index (Crohn's disease) and partial Mayo score (Ulcerative colitis). About 8% of patients reported transient adverse reactions, most commonly skin reactions, nausea and vomiting, and 2% SAEs, most frequently tachycardia. CONCLUSION: Iron isomaltoside was demonstrated to be effective and had a good safety profile in IBD patients in everyday clinical practice in Germany.

Design of the Weight-loss Endoscopy Trial (WET): a multi-center, randomized, controlled trial comparing weight loss in endoscopically implanted duodenal-jejunal bypass liners vs. intragastric balloons vs. a sham procedure.

BACKGROUND: Obesity is a global problem leading to reduced life expectancy, cardiovascular diseases, diabetes and many types of cancer. Even people willing to accept treatment only achieve a mean weight loss of about 5 kg using commercial weight loss programs. Surgical interventions, e.g. sleeve gastrectomy or gastric bypass are effective but accompanied by risk of serious complications and side effects. Less invasive endoscopic procedures mainly comprise the intragastric balloon (IB) and the duodenal-jejunal bypass liner (DJBL). To date, a randomized comparison between these devices has not been undertaken or shown to be superior to a sham procedure. METHODS: We designed a multi-center, randomized, patient and assessor-blinded, controlled trial comparing weight loss in endoscopically implanted IB vs. DJBL vs. a sham procedure. A total of 150 patients with a BMI > 35 kg/m2 or > 30 with obesity-related comorbidities and indication for proton pump inhibitors are randomized to receive either IB, DJBL or a sham gastroscopy (2:2:1 ratio). All participants undergo regular dietary consultation. The IB will be removed after 6 months, whereas the DJBL will be explanted after 12 months. All patients will receive gastroscopies at implantation and explantation of the devices or sedation without gastroscopy to maintain blinding. Main exclusion criteria are malignant diseases, peptic ulcer or previous bariatric intervention. Weight loss 12 months after explantation of the devices, changes in comorbidities, quality of life, complication rates and safety will be evaluated. DISCUSSION: This trial could help to identify the most effective and safest endoscopic device, thus determining the new standard procedure for endoscopic bariatric treatment. TRIAL REGISTRATION: 16th January 2017. DRKS00011036. Funded by the German Research Foundation (DFG).

[Drug therapy in coeliac disease - "from bench to bedside"]. / Medikamentöse Therapie der Zöliakie ­ "from bench to bedside".

Coeliac disease is one of the most common diseases worldwide, with an estimated global prevalence of 0.5 - 1 %. The disease is triggered by a combination of environmental (gluten proteins from wheat, rye or barley) and genetic factors (mainly the human leucocyte antigens HLA-DQ2 or -DQ8). At present, a strict gluten-free diet (GFD) represents the only treatment option. However, strict adherence to a GFD is challenging, since even highly motivated patients may be subject to inadvertent or background exposure to gluten. Thus, rigorous avoidance of gluten necessitates extensive constraint of patients' food choices and social interactions. Moreover, even in fully adherent patients, a GFD may fail to induce clinical or histological normalisation. New (adjunctive) non-dietary therapeutic strategies for patients with coeliac disease are therefore of great interest. In this review, on the basis of the current understanding of its pathophysiology, we examine and discuss novel pharmacological approaches for the treatment of coeliac disease.

Structural modification of resveratrol leads to increased anti-tumor activity, but causes profound changes in the mode of action.

(Z)-3,5,4'-Trimethoxystilbene (Z-TMS) is a resveratrol analog with increased antiproliferative activity towards a number of cancer cell lines compared to resveratrol, which has been shown to inhibit tubulin polymerization in vitro. The purpose of this study was to investigate if Z-TMS still shows potential for the prevention of metabolic diseases as known for resveratrol. Cell growth inhibition was determined with IC50 values for Z-TMS between 0.115µM and 0.473µM (resveratrol: 110.7µM to 190.2µM). Flow cytometric analysis revealed a G2/M arrest after Z-TMS treatment, whereas resveratrol caused S phase arrest. Furthermore, Z-TMS was shown to impair microtubule polymerization. Beneficial effects on lipid accumulation were observed for resveratrol, but not for Z-TMS in an in vitro steatosis model. (E)-Resveratrol was confirmed to elevate cAMP levels, and knockdown of AMPK attenuated the antiproliferative activity, while Z-TMS did not show significant effects in these experiments. SIRT1 and AMPK activities were further measured indirectly via induction of the target gene small heterodimer partner (SHP). Thereby, (E)-resveratrol, but not Z-TMS, showed potent induction of SHP mRNA levels in an AMPK- and SIRT1-dependent manner, as confirmed by knockdown experiments. We provide evidence that Z-TMS does not show beneficial metabolic effects, probably due to loss of activity towards resveratrol target genes. Moreover, our data support previous findings that Z-TMS acts as an inhibitor of tubulin polymerization. These findings confirm that the methylation of resveratrol leads to profound changes in the mode of action, which should be taken into consideration when conducting lead structure optimization approaches.

Clinical significance of C-reactive protein levels in predicting responsiveness to iron therapy in patients with inflammatory bowel disease and iron deficiency anemia.

BACKGROUND: Iron deficiency anemia (IDA) is a common complication of inflammatory bowel disease (IBD). In clinical practice, many patients receive initial treatment with iron tablets although intravenous (i.v.) iron supplementation is often preferable. AIM: This study investigated whether systemic inflammation at initiation of treatment (assessed by C-reactive protein [CRP] and interleukin-6 [IL-6] measurements) predicts response to iron therapy. METHODS: Data from a previously published phase III trial were retrospectively analyzed after stratification of patients according to baseline CRP (> 4 vs. ≤ 4 mg/L) and IL-6 (> 6 vs. ≤ 6 pg/mL) levels. The study population consisted of patients with Crohn's disease or ulcerative colitis and IDA (Hb ≤ 110 g/L and TSAT < 20 % or serum ferritin < 100 ng/mL), randomized to either oral (ferrous sulfate) or i.v. iron (ferric carboxymaltose). RESULTS: A total of 196 patients were evaluated (oral iron: n = 60; i.v. iron: n = 136). Baseline CRP and IL-6 levels were independent of patients' initial Hb levels and iron status (serum ferritin and TSAT; all p > 0.05). Among iron tablet-treated patients, Hb increase was significantly smaller in the high- versus low-CRP subgroup (1.1 vs. 2.0, 2.3 vs. 3.1, and 3.0 vs. 4.0 g/dL at weeks 2, 4, and 8, respectively; all p < 0.05). Differences were less pronounced with stratification according to baseline IL-6. Response to i.v. iron was mainly independent of inflammation. CONCLUSIONS: Patients with high baseline CRP achieved a lower Hb response with oral iron therapy. Our results suggest that CRP may be useful to identify IBD patients who can benefit from first-line treatment with i.v. iron to improve their IDA.

Resveratrol-induced potentiation of the antitumor effects of oxaliplatin is accompanied by an altered cytokine profile of human monocyte-derived macrophages.

The objective of this study was to investigate, whether the naturally occurring polyphenol resveratrol (Res) enhances the anti-tumor activities of the chemotherapeutic agent oxaliplatin (Ox) in a cell culture model of colorectal cancer, also with regard to a possible inflammatory response and cytotoxic side-effects. Res and Ox in combination synergistically inhibit cell growth of Caco-2 cells, which seems to be due to the induction of different modes of cell death and further leads to an altered cytokine profile of cocultured macrophages. Moreover, combinatorial treatment does not affect non-transformed cells as severe cytotoxicity is not detected in human foreskin fibroblasts and platelets.

Comparison of a new microbiological assay with a standard high-performance liquid chromatographic method for determination of vitamin B6 in serum.

BACKGROUND: A high-performance liquid chromatographic (HPLC) assay for vitamin B6 in human serum was compared with a novel microbiological assay (ID-Vit) that uses microtitre plates precoated with a specific microorganism, thus avoiding numerous problems associated with the use of stock cultures utilized by common other microbial assay mit B6. METHODS: Data obtained using HPLC were compared with 1D-Vit results in 170 healthy individuals and in 68 patients with coronary artery disease (CAD, 37 with acute coronary syndrome [ACS], 31 with stable CAD). Regression and Bland-Altman analysis were performed. Homocysteine in CAD patients was measured by HPLC. RESULTS: The ID-Vit assay correlated well with the HPLC assay (Pearson's r = 0.89 [p < 0.0001] in healthy and 0.82 [p < 0.001] in CAD individuals). Bland-Altman analyses revealed good agreement between the results of both methods in both cohorts, with > or = 95% of all values grouping within the lines of agreement. In CAD patients, mean homocysteine values did not differ between stable CAD and ACS and were normal. Thirty-seven percent of CAD patients had estimated glomerular filtration rates (GFR) below 60 mL/min/1.73m2. GFR correlated inversely with homocysteine levels (r = -0.80, p < 0.001) whereas neither HPLC nor ID-Vit values for B6 did. CONCLUSIONS: ID-Vit assay and the HPLC standard are in very good agreement. The new assay can easily be automated and is less laborious than common microbiological assays. The lack of correlation between B6 vitamin and homocysteine can be accounted for by the fact that mean vitamin B6 in our CAD patients was in the normal range and that a relevant percentage of patients had chronic renal disease.

[Efficacy and tolerability of ferric carboxymaltose in geriatric patients with anemia. Data from three non-interventional studies]. / Wirksamkeit und Verträglichkeit einer intravenösen Eisentherapie bei geriatrischen Patienten mit Anämie. Gepoolte Daten aus drei nicht-interventionellen Studien.

BACKGROUND: Anemia in the elderly is a common clinical finding. Prevalence in hospitalized geriatric patients approximates up to 40% presenting as iron deficiency anemia associated with absolute iron deficiency, anemia of chronic disease associated with functional iron deficiency or unexplained anemia. In patients with functional iron deficiency oral iron substitution is ineffective due to elevated hepcidin levels, such as in renal anemia. In these patients intravenous iron substitution represents a cornerstone. However, data among geriatric patients are limited. We conducted three non-interventional studies collecting data with respect to efficacy and tolerance of ferric carboxymaltose (ferinject) in three patient groups (cancer, chronic kidney disease [CKD], chronic inflammatory bowel disease [CIBD]) with anemia and functional iron deficiency. The present sub-analysis describes the results among the geriatric patients (age > 70 years) observed in all three observational studies. PATIENTS, METHODS: 264 patients were analyzed (mean age of 76.9 years [70-90 years; SD +/- 5.2 years]). Patients received an average amount of 1200 mg ferric carboxymaltose (746-1575 mg). RESULTS: Hemoglobin levels (p < 0.001), serum ferritin (p < 0.001) and transferrin saturation (p < 0.05) rose significantly in CKD patients; in CIBD patients hemoglobin and transferrin saturation rose significantly (p < 0.05) while the rise of ferritin failed to be significant. In oncologic patients the rise of hemoglobin and ferritin levels was of high statistic significance (p < 0.001) and transferrin saturation also rose significantly (p = 0.02) Fatigue, mental capacities as well as dyspnea improved among CKD-and CIBD-groups. No severe adverse reactions occurred. CONCLUSION: Administration of ferric carboxymaltose in geriatric patients is well tolerated and offers an effective treatment option for the treatment of functional iron deficiency.

Use of Biomarkers of Inflammation in the Differentiation of Iron Deficiency and Anaemia-Lessons from Inflammatory Bowel Disease.

Iron deficiency and iron deficiency anaemia are common in inflammatory bowel disease (IBD), to the detriment of the patients' quality of life. Since ferritin, as an acute-phase protein (APP), has limited diagnostic value in IBD, concurrent assessment of C-reactive protein (CRP) is recommended. The World Health Organization suggests using α1-acid glycoprotein (AGP) as an additional biomarker due to its differing half-life. This study aimed to evaluate ferritin levels in patients with IBD using CRP and AGP, individually and in combination. A total of 118 patients with IBD (mean age: 45.48 ± 15.25 years, 47.46% female) were recruited, including 38 with Crohn's disease, 47 with ulcerative colitis, and 33 controls. The results showed that while CRP alone detected an inflammatory increase in ferritin of 29.76%, this increased to 82.14% when AGP or both AGP and CRP were considered (p < 0.05). Elevated AGP levels were more prevalent in patients with ulcerative colitis. However, concordance between high CRP and AGP levels was confirmed in only 55% of cases. Correcting for inflammation using CRP and/or AGP significantly improved the diagnostic accuracy of ferritin levels in patients with IBD, highlighting the challenge posed by inflammation when assessing iron deficiency.

Induction and maintenance of mucosal healing in Crohn's disease with ustekinumab in clinical practice across all care levels in Germany (MUCUS).

The impact of ustekinumab (UST) on mucosal- and fistula healing and extraintestinal manifestations (EIM) in Crohn's disease (CD) were not fully elucidated in the registration trials. In this prospective, multicenter study (EudraCT number: 2017-005151-83) we evaluated the German label real-world-effectiveness of UST to achieve the primary endpoint of combined clinical and endoscopic response at week 52 and several secondary endpoints. Of 79 screened we enrolled 52 patients (female n = 28, bionaïve n = 13, biologic n = 39). At week 52 (per protocol analysis), 52% (n = 13/25) of patients achieved the primary endpoint [50% (n = 3/6) in the bionaïve, 45.5% (n = 5/11) biologic, 62.5% (n = 5/8 ) multiple biologics cohorts, respectively with age as independent predictor [OR 95% CI 0.933 (0.873, 0.998) p = 0.043], 60% (n = 15/25) achieved endoscopic response [50% (n = 3/6) in the bionaïve, 54.5% (n = 6/11) biologic, 75% (n = 6/8) multiple biologics cohorts, respectively], 36% (n = 9/25) achieved endoscopic remission [50% (n = 3/6) in the bionaïve, 27.3% (n = 3/11) biologic, 37.5% (n = 3/8) multiple biologics cohorts, respectively], 48% (n = 12/25) achieved mucosal healing [50% (n = 3/6) in the bionaïve, 36.4% (n = 4/11) biologic, 62.5% (n = 5/8) multiple biologics cohorts, respectively]. All achieved a fistula response and 33.3% (n = 1/3) in the multiple biologics group fistula remission at week 52. EIM decreased (week 0 28.2% vs. week 52 8%). CRP, FCP, PRO-2, EQ-5D-5L improved throughout. 36 patients (69.2%) experienced ≥ 1 treatment emergent adverse event, in 8 (15.4%) cases rated as severe and in 5 (9.6%) leading to UST discontinuation, but no very severe events or deaths. The effectiveness of UST was better than in the registration trials.

Iron therapy supplementation in inflammatory bowel disease patients with iron deficiency anemia: findings from a real-world analysis in Italy.

BACKGROUND: This real-world analysis evaluated iron therapy supplementation in inflammatory bowel disease patients with iron-deficiency anemia, considering disease progression and healthcare resource consumption. METHODS: A retrospective observational study was conducted using administrative databases of a pool of Italian healthcare entities, covering about 9.3 million beneficiaries. Between January 2010 and September 2017, adult patients were enrolled in the presence of either hospitalization or active exemption code for ulcerative colitis/Crohn's disease, or one vedolizumab prescription. Iron-deficiency anemia was identified by at least one prescription for iron and/or hospitalization for iron-deficiency anemia and/or blood transfusion (proxy of diagnosis). Patients were divided in untreated and iron-treated during 12-month follow-up and analyzed before and after propensity score matching. Disease progression, was evaluated through inflammatory bowel disease-related hospitalizations and surgeries, and healthcare resource utilization was assessed. RESULTS: Overall, 1753 patients were included, 1077 (61.4%) treated with iron therapy and 676 (38.6%) untreated. After propensity score matching, 655 patients were included in each group. In unbalanced cohorts, disease progression was significantly reduced in patients receiving iron therapy compared to the untreated (11.0% vs. 15.7%, P  < 0.01), and this trend was maintained also after applying propensity score matching. The overall mean cost/patient was significantly lower in iron-treated than untreated (4643€ vs. 6391€, P  < 0.01). CONCLUSION: The findings of this real-world analysis suggest that iron therapy was associated with significant benefits in inflammatory bowel disease patients with iron-deficiency anemia, in terms of both disease progression and healthcare resource utilization.

Ferric carboxymaltose prevents recurrence of anemia in patients with inflammatory bowel disease.

BACKGROUND & AIMS: Iron-deficiency anemia is the most common systemic complication of inflammatory bowel diseases (IBD). Iron-deficiency anemia recurs frequently and rapidly after iron-replacement therapy in patients with IBD. We performed a randomized, placebo-controlled trial to determine if administration of ferric carboxymaltose (FCM) prevents anemia in patients with IBD and low levels of serum ferritin. METHODS: We performed a single-blind, multicenter study of nonanemic patients who had completed the FERGIcor study. Serum levels of ferritin were assessed every second month, and patients were given FCM (total iron dose, 1181 ± 662 mg; n = 105) or placebo (n = 99) when levels decreased to less than 100 µg/L. The primary end point was time to recurrence of anemia within 8 months. Secondary end points included changes of quality of life, disease activity, results from laboratory tests, and adverse events. RESULTS: Anemia recurred in 26.7% of subjects given FCM and in 39.4% given placebo. The time to anemia recurrence was longer in the FCM group (hazard ratio, 0.62; 95% confidence interval, 0.38-1.00; P = .049). Markers of body levels of iron increased or remained at normal levels in subjects given FCM (ferritin increased by 30.3 µg/L, transferrin saturation increased by 0.6%) but decreased in the group given placebo (ferritin decreased by 36.1 µg/L, transferrin saturation decreased by 4.0%). Changes in quality of life and disease activity were comparable between groups. Adverse events were reported in 59.0% of the FCM group and 50.5% of the placebo group, and serious adverse events were reported in 6.7% and 8.1%, respectively. CONCLUSIONS: FCM prevents recurrence of anemia in patients with IBD, compared with placebo. Nevertheless, the high rate of anemia recurrence warrants optimization of the frequency and requirements for FCM treatment.