Geert D'Haens

Academisch Medisch Centrum Universiteit van Amsterdam, Amsterdamo, North Holland, Netherlands

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Publications (384)3702.99 Total impact

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    ABSTRACT: Background and aims: Ciclosporin A (CsA) and infliximab (IFX) are similarly effective in preventing short-term colectomy in ulcerative colitis (UC) patients, but long-term data are scarce. We aimed to compare short- and long-term efficacy of CsA and IFX by analysing colectomy rates and failure of remission-induction treatment as outcome parameters for treatment success. Methods: We retrospectively studied hospitalised UC patients who received CsA or IFX for moderate-to-severe UC, between January 2000 and April 2014. The primary end point was time to colectomy, and treatment failure (defined as colectomy or another remission-induction treatment with corticosteroids, CsA or IFX) was used as secondary end point. Variables possibly affecting colectomy outcomes were analysed. Results: Fifty-five patients were studied for colectomy outcome and 58 patients for treatment failure. A significantly longer follow-up duration was available for CsA-treated patients (P<0.001, both subcohorts). Patients showed comparable patient- and disease-specific characteristics. Colectomy rates did not differ significantly at 3, 12 and 36 months: 36% versus 29%, 58% versus 48%, and 64% versus 67% for CsA- and IFX-treated patients, respectively. Multivariate Cox regression analysis revealed the lowest hazard ratio for colectomy in patients concomitantly using thiopurines (HR 0.28 (CI 0.13-0.64), P=0.002). Treatment failure rates were not significantly different at 3, 12 and 36 months: 35% versus 48%, 51% versus 68%, and 62% versus 83% for CsA- and IFX-treated patients, respectively. Conclusion: Treatment with CsA and IFX is similarly effective in preventing short- and long-term colectomy in hospitalised UC patients. Furthermore, failure rates of these remission-induction treatments were comparable.
    No preview · Article · Jan 2016 · Journal of Crohn s and Colitis
  • Diane R Mould · Geert D'Haens · Richard N Upton
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    ABSTRACT: Therapeutic drug monitoring; inflammatory disease; monoclonal antibodies; individualized therapy; dashboards; personalized medicines
    No preview · Article · Jan 2016 · Clinical Pharmacology &#38 Therapeutics
  • A.S. Strik · S.J.A. Bots · G D'Haens · M Löwenberg
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    ABSTRACT: After the introduction of anti-tumor necrosis factor (anti-TNF) agents, the clinical outcome of patients with Inflammatory Bowel Disease (IBD) has improved significantly. However, use of anti-TNF therapy is complicated by loss of response. In order to maintain remission, adequate serum levels are required. Hence, therapeutic drug monitoring (TDM) is important in order to optimize serum drug levels, especially in patients with loss of response to these agents. Optimization of anti-TNF therapy by applying TDM enables clinicians to regain response to TNF blockers in a significant proportion of patients. It is important to use anti-TNF agents in their most optimal way, since these therapeutic agents are expensive and the medical options after failing anti-TNF therapy are limited. Here, we will discuss how to optimize treatment with anti-TNF agents in IBD patients in order to improve treatment efficacy, prevent anti-drug antibody formation, reduce side effects, discontinue unnecessary treatment and manage costs.
    No preview · Article · Dec 2015 · Expert Review of Clinical Pharmacology
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    ABSTRACT: Objective: Infliximab maintenance treatment for Crohn's disease (CD) consists of intravenous infusions that are usually given at 6-8-week intervals. We aimed to evaluate whether home-based infliximab infusions could offer a useful and safe alternative for the management of CD patients. Methods: Adult CD patients receiving infliximab maintenance treatment at the Academic Medical Center in Amsterdam were invited to receive their infusions at home for the duration of 1 year. Patients had to be in clinical remission and should have had no adverse events during previous infusions. Patient satisfaction and experience were studied. Costs were analyzed and compared with hospital-based infliximab infusions. Results: Twenty-nine patients were invited, of whom 13 (45%) wanted to participate. Of the participants, 54% were female, and the median age was 33 years. In total, 59 infliximab infusions were administered at home at a median dose of 360 mg. The median rating of patient satisfaction was 8 on a scale from 1 to 10 for both home and hospital treatment settings. An important observation was that patients' willingness to participate would have been 70% if the possibility of receiving infusions at home outside office hours had been offered. Costs of infliximab infusions at home were &OV0556;229 per infusion compared with &OV0556;284 at the infusion clinic (excluding drug costs). Conclusion: Home-based infliximab infusions were associated with a cost saving of &OV0556;55 per infusion. Most participants were satisfied and would recommend home-based infusions to others. Infliximab treatment at home might be recommended as routine care for CD patients.
    No preview · Article · Nov 2015 · European journal of gastroenterology & hepatology
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    ABSTRACT: Objective: Although the Geboes score (GS) and modified Riley score (MRS) are commonly used to evaluate histological disease activity in UC, their operating properties are unknown. Accordingly, we developed an alternative instrument. Design: Four pathologists scored 48 UC colon biopsies using the GS, MRS and a visual analogue scale global rating. Intra-rater and inter-rater reliability for each index and individual index items were measured using intraclass correlation coefficients (ICCs). Items with high reliability were used to develop the Robarts histopathology index (RHI). The responsiveness/validity of the RHI and multiple histological, endoscopic and clinical outcome measures were evaluated by analyses of change scores, standardised effect size (SES) and Guyatt's responsiveness statistic (GRS) using data from a clinical trial of an effective therapy. Results: Inter-rater ICCs (95% CIs) for the total GS and MRS scores were 0.79 (0.63 to 0.87) and 0.80 (0.69 to 0.87). The correlation estimates between change scores in RHI and change score in GS and MRS were 0.75 (0.67 to 0.82) and 0.84 (0.79 to 0.88), respectively. The SES and GRS estimates for GS, MRS and RHI were: 1.87 (1.54 to 2.20) and 1.23 (0.97 to 1.50), 1.29 (1.02 to 1.56) and 0.88 (0.65 to 1.12), and 1.05 (0.79 to 1.30) and 0.88 (0.64 to 1.12), respectively. Conclusions: The RHI is a new histopathological index with favourable operating properties.
    Full-text · Article · Oct 2015 · Gut
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    ABSTRACT: Background Patient-reported outcomes (PROs) have an increasingly important role in the evaluation of new therapies for inflammatory bowel disease. The US Food and Drug Administration has issued formal guidance to describe the role of PRO instruments in evaluation of claims for product labelling. However, no validated PRO exists for ulcerative colitis.AimTo investigate whether the PROs from the Mayo Clinic Score (MCS) for UC can be modified, to develop an interim PRO for use in clinical trials, alone or in combination with endoscopy.Methods Data from an induction trial of a mesalazine (mesalamine) formulation were used to compare effect sizes between mesalazine and placebo for PRO items (stool frequency and rectal bleeding) alone and in combination with endoscopy. The operating properties of the PRO were validated using data from a phase 2 trial of MLN02, a humanised antibody to the α4β7 integrin in patients with UC.ResultsA two-item PRO (PRO2) consisting of rectal bleeding = 0 and stool frequency ≤1 or ≤2, combined with an endoscopy subscore ≤1 yielded statistically significant differences between active drug and placebo. This combination yielded the most similar effect sizes and placebo rates for remission, compared to the primary trials. Use of PRO items alone yielded high placebo remission rates in both data sets, although rates were lower when the items were combined and remission defined as PRO2 = 0.Conclusion Patient-reported outcomes items derived from the Mayo Clinic Score combined with endoscopy as a co-primary endpoint may be an appropriate interim outcome measure for ulcerative colitis trials.
    Full-text · Article · Sep 2015 · Alimentary Pharmacology & Therapeutics
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    ABSTRACT: Background Anti-tumour necrosis factor (anti-TNF) monoclonal antibodies have shown efficacy in inflammatory bowel diseases (IBD). As these therapies lose patent protection, biosimilar versions of the originator products are being developed, such as the infliximab biosimilar CT-P13; however, some uncertainty exists regarding their pharmacology in IBD.AimTo review the literature on anti-TNF biosimilars focusing on pharmacokinetics, pharmacodynamic properties and comparative effectiveness, related to their use in IBD.MethodsA PubMed literature search was performed using the following terms individually or in combination: ‘biosimilars,’ ‘CT-P13,’ ‘Crohn's disease,’ ‘inflammatory bowel disease,’ ‘ulcerative colitis,’ ‘anti-TNFα therapy,’ ‘infliximab,’ ‘adalimumab,’ ‘pharmacokinetics,’ ‘immunogenicity.’ResultsBioequivalence of CT-P13 and infliximab was shown in ankylosing spondylitis (AS) and therapeutic equivalence in rheumatoid arthritis (RA). Preliminary results of CT-P13 in IBD come from small post-marketing registries and case series with a relatively short-term follow-up period and suggest comparable efficacy and safety to infliximab. Inter- and intra-individual differences in exposure and response are well known for the original molecules but dosing regimens and concomitant medications are different for RA compared to IBD, limiting the ability to translate some of the pharmacology data in RA to IBD. Uncertainty exists about cross-reactivity of anti-drug antibodies and whether similar exposure–response relationships will be observed for biosimilars and efficacy thresholds for therapeutic drug monitoring can be used interchangeably.Conclusions It is likely that biosimilars will be widely used for the treatment of IBD due to their cost savings and comparable efficacy. Nevertheless, robust post-marketing studies and pharmacovigilance are warranted in the coming years.
    No preview · Article · Sep 2015 · Alimentary Pharmacology & Therapeutics
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    ABSTRACT: Background: Crohn's disease (CD) is a chronic disabling and progressive IBD. Only strategies looking beyond symptoms and based on tight monitoring of objective signs of inflammation such as mucosal lesions may have the potential for disease modification. Endoscopic evaluation is currently the gold standard to assess mucosal lesions and has become a major therapeutic endpoint in clinical trials. Several endoscopic indices have been proposed to evaluate disease activity; unvalidated and arbitrary definitions have been used in clinical trials for defining endoscopic response and endoscopic remission in CD. Methods: In these recommendations from the International Organization for the Study of Inflammatory Bowel Disease, we first reviewed all technical aspects of available endoscopic scoring systems in the literature. Second, in order to achieve consensus on endoscopic definitions of remission and response in trials, a two-round vote based on a Delphi method was performed among 14 specialists in the field of IBDs. Results: At the end of the voting process, the investigators ranked first a >50% decrease in Simple Endoscopic Score for Crohn's Disease (SES-CD) or Crohn's Disease Endoscopic Index of Severity for the definition of endoscopic response, and an SES-CD 0-2 for the definition of endoscopic remission in CD. All experts agreed on a Rutgeerts' score i0-i1 for the definition of endoscopic remission after surgery.
    No preview · Article · Sep 2015 · Gut
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    ABSTRACT: Conventional management of Crohn's disease features incremental use of therapies. However, early combined immunosuppression (ECI), with a TNF antagonist and antimetabolite might be a more effective strategy. We compared the efficacy of ECI with that of conventional management for treatment of Crohn's disease. In this open-label cluster randomised controlled trial (Randomised Evaluation of an Algorithm for Crohn's Treatment, REACT), we included community gastroenterology practices from Belgium and Canada that were willing to be assigned to either of the study groups, participate in all aspects of the study, and provide data on up to 60 patients with Crohn's disease. These practices were randomly assigned (1:1) to either ECI or conventional management. The computer-generated randomisation was minimised by country and practice size. Up to 60 consecutive adult patients were assessed within practices. Patients who were aged 18 years or older; documented to have Crohn's disease; able to speak or understand English, French, or Dutch; able to access a telephone; and able to provide written informed consent were followed up for 2 years. The primary outcome was the proportion of patients in corticosteroid-free remission (Harvey-Bradshaw Index score ≤4) at 12 months at the practice level. This trial is registered with ClinicalTrials.gov, number NCT01030809. This study took place between March 15, 2010, and Oct 1, 2013. Of the 60 practices screened, 41 were randomly assigned to either ECI (n=22) or conventional management (n=19). Two practices (one in each group) discontinued because of insufficient resources. 921 (85%) of the 1084 patients at ECI practices and 806 (90%) of 898 patients at conventional management practices completed 12 months follow-up and were included in an intention-to-treat analysis. The 12 month practice-level remission rates were similar at ECI and conventional management practices (66·0% [SD 14·0] and 61·9% [16·9]; adjusted difference 2·5%, 95% CI -5·2% to 10·2%, p=0·5169). The 24 month patient-level composite rate of major adverse outcomes defined as occurrence of surgery, hospital admission, or serious disease-related complications was lower at ECI practices than at conventional management practices (27·7% and 35·1%, absolute difference [AD] 7·3%, hazard ratio [HR]: 0·73, 95% CI 0·62 to 0·86, p=0·0003). There were no differences in serious drug-related adverse events. Although ECI was not more effective than conventional management for controlling Crohn's disease symptoms, the risk of major adverse outcomes was lower. The latter finding should be considered hypothesis-generating for future trials. ECI was not associated with an increased risk of serious drug-related adverse events or mortality. AbbVie Pharmaceuticals. Copyright © 2015 Elsevier Ltd. All rights reserved.
    No preview · Article · Sep 2015 · The Lancet
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    ABSTRACT: Background Many patients with active Crohn's disease do not adequately respond to therapies, highlighting the need for new treatments.AimsTo conduct a randomised, double-blind, placebo-controlled phase 3 study to assess the efficacy and safety of vercirnon, an oral inhibitor of CC chemokine receptor-9, for the treatment of patients with moderately-to-severely active Crohn's disease.Methods Patients with a Crohn's Disease Activity Index (CDAI) of 220–450, plus evidence of active disease (endoscopically confirmed or elevation of both C-reactive protein and faecal calprotectin), who had failed corticosteroid or immunosuppressant therapy were enrolled. Patients were equally randomised to receive placebo, vercirnon 500 mg once daily or vercirnon 500 mg twice daily. The primary endpoint was clinical response, defined as a 100-point decrease in CDAI from baseline to week 12.ResultsSix hundred and eight patients were randomised. Patient characteristics and baseline demographics were similar among the groups. The proportions of patients achieving a clinical response were 25.1%, 27.6% and 27.2% for placebo, once daily and twice daily respectively; treatment differences were not significant (2.5%; 95% confidence interval, CI −6.1% to 11.0%, P = 0.546 for once daily vs. placebo, and 2.1%; 95% CI −6.5% to 10.7%, P = 0.648 for twice daily vs. placebo). Adverse events were reported in 69.8%, 73.3% and 78.1% with serious adverse events in 8.9%, 5.9%, and 6.0% of patients in the placebo, once-daily and twice-daily groups, respectively.Conclusions We did not demonstrate efficacy of vercirnon as an induction therapy in patients with moderately-to-severely active Crohn's disease; its effect in maintenance therapy was not addressed.
    No preview · Article · Sep 2015 · Alimentary Pharmacology & Therapeutics
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    ABSTRACT: The Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) program was initiated by the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD). It examined potential treatment targets for inflammatory bowel disease (IBD) to be used for a "treat-to-target" clinical management strategy using an evidence-based expert consensus process. A Steering Committee of 28 IBD specialists developed recommendations based on a systematic literature review and expert opinion. Consensus was gained if ≥75% of participants scored the recommendation as 7-10 on a 10-point rating scale (where 10=agree completely). The group agreed upon 12 recommendations for ulcerative colitis (UC) and Crohn's disease (CD). The agreed target for UC was clinical/patient-reported outcome (PRO) remission (defined as resolution of rectal bleeding and diarrhea/altered bowel habit) and endoscopic remission (defined as a Mayo endoscopic subscore of 0-1). Histological remission was considered as an adjunctive goal. Clinical/PRO remission was also agreed upon as a target for CD and defined as resolution of abdominal pain and diarrhea/altered bowel habit; and endoscopic remission, defined as resolution of ulceration at ileocolonoscopy, or resolution of findings of inflammation on cross-sectional imaging in patients who cannot be adequately assessed with ileocolonoscopy. Biomarker remission (normal C-reactive protein (CRP) and calprotectin) was considered as an adjunctive target. Evidence- and consensus-based recommendations for selecting the goals for treat-to-target strategies in patients with IBD are made available. Prospective studies are needed to determine how these targets will change disease course and patients' quality of life.Am J Gastroenterol advance online publication, 25 August 2015; doi:10.1038/ajg.2015.233.
    Full-text · Article · Aug 2015 · The American Journal of Gastroenterology
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    ABSTRACT: This randomised, open-label, phase I/II study evaluated the efficacy and safety of nintedanib, an oral, triple angiokinase inhibitor, combined with chemotherapy, relative to bevacizumab plus chemotherapy as first-line therapy in patients with metastatic colorectal cancer (mCRC). Patients with histologically confirmed mCRC (adenocarcinoma), an Eastern Cooperative Oncology Group performance status ≤2 and adequate organ function were included. Patients were randomised 2:1 to receive nintedanib 150 mg or 200 mg b.i.d. plus mFOLFOX6 (oxaliplatin 85 mg/m(2), l-leucovorin 200 mg/m(2) or d,l-leucovorin 400 mg/m(2), 5-fluoruracil bolus 400 mg/m(2) followed by 2400 mg/m(2), every 2 weeks) or bevacizumab (5 mg/kg every 2 weeks) plus mFOLFOX6. During phase I, patients underwent a 3 + 3 dose-escalation schema to determine the maximum tolerated dose (MTD) of nintedanib in combination with mFOLFOX6. The primary end point was progression-free survival (PFS) rate at 9 months. Objective response (OR) was a secondary end point. The nintedanib recommended phase II dose was 200 mg b.i.d. plus mFOLFOX6 based on safety data from phase I (n = 12). Of 128 patients randomised in the phase II part, 126 received treatment (nintedanib plus mFOLFOX6, n = 85; bevacizumab plus mFOLFOX6, n = 41). PFS at 9 months was 62.1% with nintedanib and 70.2% with bevacizumab [difference: -8.1% (95% confidence interval -27.8 to 11.5)]. Confirmed ORs were recorded in 63.5% and 56.1% of patients in the nintedanib and bevacizumab groups, respectively. The incidence of adverse events (AEs) considered related to treatment was 98.8% with nintedanib and 97.6% with bevacizumab; the incidence of serious AEs was 37.6% with nintedanib and 53.7% with bevacizumab. The pharmacokinetics of nintedanib and the components of mFOLFOX6 were unaffected by their combination. Nintedanib in combination with mFOLFOX6 showed efficacy as first-line therapy in patients with mCRC with a manageable safety profile and further studies in this population are warranted. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
    No preview · Article · Aug 2015 · Annals of Oncology
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    ABSTRACT: Background Intestinal fibrosis is a process driven by chronic inflammation leading to increased presence of myofibroblasts and collagen deposition. Although strictures are rarely seen in ulcerative colitis (UC), longstanding disease is believed to cause fibrosis resulting in altered bowel function.Methods The presence of fibrosis was studied in colectomy specimens from patients with recent onset UC refractory to medical treatment (n=13) and longstanding UC (n=16), and colon cancer patients without UC (n=7) as controls. Severity of inflammation was scored according to the Geboes score on haematoxylin and eosin stainings. Immunohistochemistry was performed to detect α-smooth muscle actin, fibronectin and collagen I and III.ResultsColectomy specimens from patients with acute UC showed significantly more inflammation than those with longstanding disease (19 vs 9 points, p=0.01). Both acute and longstanding UC showed a thicker muscularis mucosa than controls (0.10 vs 0.10 vs 0.05 mm, p=0.019). An increase in collagen I and III deposition in the mucosa was observed in UC compared to controls (40% (30-75) versus 25% (10-25), p=0.033), but this did not differ significantly among acute and longstanding UC patients.Conclusion Collagen deposition is enhanced in UC compared to controls. However, UC collagen deposition does not increase significantly over time and does not seem to aggravate the entire fibrotic process. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.
    No preview · Article · Aug 2015 · Journal of Crohn s and Colitis
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    ABSTRACT: Background Associations between patient-reported outcomes and mucosal healing have not been established in ulcerative colitis (UC).AimTo evaluate relationships of rectal bleeding and stool frequency with mucosal healing and quality of life (QoL) in patients with UC in two Phase 3 studies (ULTRA 1 and 2).Methods Associations of patient-reported rectal bleeding and stool frequency subscores with mucosal healing (Mayo endoscopy subscore = 0 or 0/1) and QoL [inflammatory bowel disease questionnaire (IBDQ)] were assessed in adalimumab-randomised patients (160/80 mg at Weeks 0/2 followed by 40 mg biweekly or weekly) at Weeks 8 (n = 433) and 52 (n = 299), and in patients with mucosal healing [endoscopy subscore = 0 (n = 17); 0/1 (n = 52)] at Weeks 8 and 52.ResultsAt Week 8, the positive predictive values (PPVs) of rectal bleeding subscore = 0, stool frequency subscore = 0 or both scores = 0 for endoscopy subscore = 0/1 were 69%, 84% and 90% respectively; all proportions increased at Week 52. Equivalent PPVs for these subscores in patients with endoscopy subscore = 0 were 26%, 37% and 46% respectively. Among patients with endoscopy subscore = 0 at Week 8, 87% reported no rectal bleeding, while only 29% reported normal stool frequency; these proportions had increased to 94% and 41% respectively, at Week 52. Among patients with mucosal healing, IBDQ scores trended highest for patients with both rectal bleeding and stool frequency subscores = 0.Conclusions Absence of rectal bleeding and normal stool frequency are often predictive of mucosal healing and QoL, but complete normalisation of stool frequency is encountered rarely in patients with mucosal healing.
    Preview · Article · Aug 2015 · Alimentary Pharmacology & Therapeutics
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    ABSTRACT: Currently there is no guideline for the treatment of patients with Crohn's disease and high perianal fistulas. Most patients receive anti-TNF medication, but no long-term results of this expensive medication have been described, nor has its efficiency been compared to surgical strategies. With this study, we hope to provide treatment consensus for daily clinical practice with reduction in costs. This is a multicentre, randomized controlled trial. Patients with Crohn's disease who are over 18 years of age, with newly diagnosed or recurrent active high perianal fistulas, with one internal opening and no anti-TNF usage in the past three months will be considered. Patients with proctitis, recto-vaginal fistulas or anal stenosis will be excluded. Prior to randomisation, an MRI and ileocolonoscopy are required. All treatment will start with seton placement and a course of antibiotics. Patients will then be randomised to: (1) chronic seton drainage (with oral 6-mercaptopurine (6MP)) for one year, (2) anti-TNF medication (with 6MP) for one year (seton removal after six weeks) or (3) advancement plasty after eight weeks of seton drainage (under four months anti-TNF and 6MP for one year). The primary outcome parameter is the number of patients needing fistula-related re-intervention(s). Secondary outcomes are the number of patients with closed fistulas (based on an evaluated MRI score) after 18 months, disease activity, quality of life and costs. The PISA trial is a multicentre, randomised controlled trial of patients with Crohn's disease and high perianal fistulas. With the comparison of three generally accepted treatment strategies, we will be able to comment on the efficiency of the various treatment strategies, with respect to several long-term outcome parameters. Nederlands Trial Register identifier: NTR4137 (registered on 23 August 2013).
    Full-text · Article · Aug 2015 · Trials
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    ABSTRACT: Centralized endoscopic scoring may reduce variability, but evidence is lacking in patients with Crohn's disease. We assessed the agreement of endoscopic scorings between site endoscopists and one central reader by using data from the adalimumab Crohn's disease clinical trial EXTEND. Agreement between readers for Crohn's Disease Endoscopic Index of Severity (CDEIS)-scored endoscopies from 6 sites and Simple Endoscopic Score for Crohn's Disease (SES-CD)-scored endoscopies from 19 sites in EXTEND was evaluated at baseline and weeks 12 and 52. Agreement on total scores was calculated by using intraclass correlation coefficient (ICC). Kappa statistic or Spearman correlation coefficient measured the agreement between readers for each ileocolonic segment on CDEIS variables including deep ulceration, surface involved, and ulcerated surface and SES-CD variables including ulcerated surface, size of ulcers, and affected surface. ICCs on mean scores at baseline and weeks 12 and 52 were 0.78, 0.92, and 0.86 (CDEIS), and 0.77, 0.86, and 0.82 (SES-CD), respectively. Site endoscopists consistently reported higher scores. High agreement was observed for most segments and all time points for CDEIS variables and SES-CD large ulcers. Weak agreement occurred for the right side of the colon at all time points for CDEIS deep ulceration and SES-CD large ulcers and at baseline and week 12 for CDEIS ulcerated surface. Fair/moderate agreement occurred for SES-CD ulcerated surface and moderate/high agreement for affected surface for all segments and time points. Site and central readers showed high agreement on total CDEIS and SES-CD scores overall, whereas variability for individual segments was observed. Weakest agreement occurred at baseline, with a greater difference for SES-CD than for CDEIS score. (Clinical trial registration number: NCT00348283.). Copyright © 2015 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.
    No preview · Article · Jul 2015 · Gastrointestinal endoscopy
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    ABSTRACT: High serum concentrations of Infliximab (IFX) and Adalimumab (ADA) may be associated with adverse effects in patients with inflammatory bowel disease (IBD). We aimed to investigate whether high anti-TNF trough levels (TLs) were associated with toxicity and impaired quality of life (QoL). We conducted a prospective cohort study in IBD patients in clinical and biochemical remission on IFX or ADA maintenance therapy. Trough serum concentrations and antidrug antibodies were measured in addition to biochemical markers of inflammation in serum and stool to confirm quiescent disease. QoL was assessed using IBDQ and SF-36. Side effects such as fatigue and arthralgia were measured with a visual analogue score. Skin toxicity was reported with an EORTC derived score. 252 IBD patients on maintenance anti-TNF therapy were screened, of whom 95 (73 CD, 22 UC; 72 IFX, 23 ADA) were in clinical and biochemical remission and included. Median TLs were 5.5ug/ml and 6.6 ug/ml for IFX and ADA, respectively. Patients with anti-TNF TLs above median had lower IBDQ scores than patients with lower TLs (IBDQ 176 vs. 187, P=0.02), particularly regarding systemic symptoms and emotional status. A trend towards lower SF-36 and higher fatigue scores was observed in the higher anti-TNF TL group. Skin and arthralgia scores were not significantly different between both groups. IBD patients with higher anti-TNF serum concentrations had significantly lower disease-specific QoL. Fatigue, arthralgia and skin lesions do not occur more often in these patients. This data is reassuring that high serum concentrations of anti-TNF antibodies are not toxic. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.
    No preview · Article · Jun 2015 · Journal of Crohn s and Colitis
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    ABSTRACT: Cumulative safety and tolerability of budesonide MMX(®), a once-daily oral corticosteroid for inducing mild to moderate ulcerative colitis remission, was examined. Data from three randomized, double-blind, placebo-controlled, phase II or III studies (budesonide MMX 9 mg, 6 mg, or 3 mg for 8 weeks); one phase II study (randomization to budesonide MMX 9 mg or placebo for 4 weeks, then open-label budesonide MMX 9 mg for 4 weeks); and one open-label study (budesonide MMX 9 mg for 8 weeks) were pooled. Patients randomized to budesonide MMX 9 mg (n = 288), 6 mg (n = 254), or placebo (n = 293) had similar rates of adverse events (AEs) (27.1%, 24.8%, and 23.9%) and serious AEs (2.4%, 2.0%, and 2.7%); treatment-related AEs and serious AEs were reported by 11.8% and 13.5%, and 5.9% and 2.2%, respectively, of patients receiving budesonide MMX 3 mg (n = 17) or open-label budesonide MMX 9 mg (n = 89). Mean morning plasma cortisol concentrations were normal from baseline to final visit across randomized groups; in patients receiving open-label budesonide, mean cortisol concentration was 129.9 nmol/l after 4 weeks, returning to normal concentrations at final visit. Budesonide MMX was not associated with an overall increased risk for glucocorticoid-related adverse effects. Budesonide MMX 9 mg was associated with normal mean cortisol concentrations at final visit and an AE incidence comparable to placebo. Overall, budesonide MMX was safe and well tolerated for inducing remission of patients with mild to moderate ulcerative colitis. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.
    Preview · Article · Jun 2015 · Journal of Crohn s and Colitis
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    Mark Löwenberg · Geert D'Haens
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    ABSTRACT: Various novel drugs have recently been evaluated in clinical trials showing promising effects in patients with inflammatory bowel disease (IBD). Here, we summarize the recent literature in the area of emerging therapies in the field of IBD, with specific focus on anti-integrin antibodies, such as vedolizumab (anti-α4β7) and etrolizumab (anti-rhuMAb β7), and the Janus kinase (JAK) inhibitor tofacitinib. Moreover, we will discuss efficacy and safety data of golimumab (a new subcutaneous anti-tumor necrosis factor (TNF) antibody), Avaxia (an orally delivered anti-TNF antibody), and Budesonide MMX; all have been developed for the treatment of ulcerative colitis. Other therapeuticals that might find their way to the market the coming years include the anti-mucosal vascular addressin cell adhesion molecule (MAdCAM) PF-00547659, small molecules (including laquinimod and the CCR9 antagonist Vercirnon), as well as an orally active SMAD7 antisense oligonucleotide that showed clinical benefit in Crohn's disease patients.
    Preview · Article · Jun 2015 · Current Gastroenterology Reports
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    ABSTRACT: Mucosal healing is an important treatment end-point in inflammatory bowel disease, and achieving mucosal healing has been demonstrated to improve disease-related outcomes. Considerable uncertainty exists, however, regarding the optimal approach for the assessment of mucosal healing. to compare currently available diagnostic tools for the assessment of mucosal healing and outline the ideal approach to integrating these tools into clinical trials and clinical practice. Review article. Endoscopy represents the criterion standard for the assessment of mucosal healing, and frequent endoscopic assessment is associated with a higher rate of achieving mucosal healing. The use of mucosal biopsy allows for the identification of persistent histologic disease activity, but the incremental clinical benefit of achieving histologic healing is yet to be determined. Magnetic resonance enterography has a high sensitivity for ulcer healing in endoscopically inaccessible disease activity. However, the presence of mucosal lesions cannot be reliably excluded based on this modality alone, and further small-bowel endoscopy should be considered in symptomatic patients. Video capsule endoscopy or device-assisted enteroscopy can be used, with device-assisted enteroscopy being preferred in stricturing Crohn's disease because of the risk of capsule retention or in patients in whom small-bowel malignancy is a possibility. Endoscopy remains the criterion standard for the assessment of mucosal healing. Several alternative diagnostic modalities have become available that can be of value in specific clinical circumstances, particularly in patients with small-bowel involvement. Copyright © 2015 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.
    No preview · Article · May 2015 · Gastrointestinal endoscopy

Publication Stats

16k Citations
3,702.99 Total Impact Points

Institutions

  • 2011-2016
    • Academisch Medisch Centrum Universiteit van Amsterdam
      • • Academic Medical Center
      • • Department of Gastroenterology and Hepatology
      Amsterdamo, North Holland, Netherlands
    • Academic Medical Center (AMC)
      Amsterdamo, North Holland, Netherlands
  • 2014-2015
    • Robarts Research Institute
      London, Ontario, Canada
  • 2010-2015
    • University of Amsterdam
      • Department of Gastroenterology and Hepatology
      Amsterdamo, North Holland, Netherlands
  • 2006-2015
    • Imeldaziekenhuis Bonheiden
      Bonheyden, Flanders, Belgium
  • 1999-2012
    • Universitair Ziekenhuis Ghent
      • Department of Gastroenterology
      Gand, Flemish, Belgium
  • 1993-2009
    • Universitair Ziekenhuis Leuven
      • Department of Gastroenterology
      Louvain, Flanders, Belgium
  • 2007
    • The University of Western Ontario
      • Robarts Research Institute
      London, Ontario, Canada
    • University Medical Center Utrecht
      Utrecht, Utrecht, Netherlands
  • 2004
    • University General Hospital
      Houston, Texas, United States
  • 1997-2004
    • University of Leuven
      Louvain, Flanders, Belgium
  • 1995
    • Catholic University of Louvain
      Лувен-ла-Нев, Walloon, Belgium