Publications by authors named "Frank Hoentjen"

104 Publications

Patients Prioritize a Low-volume Bowel Preparation in Colitis-associated Colorectal Cancer Surveillance: A Discrete Choice Experiment.

Inflamm Bowel Dis 2021 Sep 6. Epub 2021 Sep 6.

Department of Gastroenterology and Hepatology, Elisabeth-TweeSteden Hospital, Tilburg, the Netherlands.

Background: Patients with inflammatory bowel disease (IBD) undergo surveillance colonoscopies at fixed intervals to reduce the risk of colorectal cancer (CRC). Taking patients' preferences for determining surveillance strategies into account could improve adherence and patient satisfaction. This study aimed to determine patient preferences for CRC surveillance in IBD.

Methods: We conducted a web-based, multicenter, discrete choice experiment among adult IBD patients with an indication for surveillance. Individuals were repeatedly asked to choose between 3 hypothetical surveillance scenarios. The choice tasks were based on bowel preparation (0.3-4 L), CRC risk reduction (8% to 1%-6%), and interval (1-10 years). Attribute importance scores, trade-offs, and willingness to participate were calculated using a multinomial logit model. Latent class analysis was used to identify subgroups with similar preferences.

Results: In total, 310 of 386 sent out questionnaires were completed and included in the study. Bowel preparation was prioritized (attribute importance score 40.5%) over surveillance interval and CRC risk reduction (31.1% and 28.4%, respectively). Maximal CRC risk reduction, low-volume bowel preparation (0.3 L laxative with 2 L clear liquid) with 2-year surveillance was the most preferred combination. Three subgroups were identified: a "surveillance avoidant," "CRC risk avoidant," and "surveillance preferring" groups. Membership was correlated with age, educational level, perceived CRC risk, the burden of bowel preparation, and colonoscopies.

Conclusions: Inflammatory bowel disease patients consider bowel preparation as the most important element in acceptance of CRC surveillance. Heterogeneity in preferences was explained by 3 latent subgroups. These findings may help to develop an individualized endoscopic surveillance strategy in IBD patients.
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http://dx.doi.org/10.1093/ibd/izab221DOI Listing
September 2021

Patients' perspectives on a drug safety monitoring system for immune-mediated inflammatory diseases based on patient-reported outcomes.

Expert Opin Drug Saf 2021 Aug 12:1-8. Epub 2021 Aug 12.

Netherlands Pharmacovigilance Centre Lareb, 's-hertogenbosch, The Netherlands.

Background: Patient-reported outcomes (PROs) on adverse drug reactions (ADRs) are increasingly used in cohort event monitoring (CEM) to obtain a better understanding of patients' real-world experience with drugs. Despite the leading role for patients, little is known about their perspectives on CEM systems.

Research Design And Methods: In a cross-sectional open survey following the rationale of the Technology Acceptance Model, we aimed to obtain insight in patients' perspectives on the perceived usefulness, ease of use and attitude toward using a PRO-based drug safety monitoring system for ADRs attributed to biologics.

Results: Patients considered structural reporting of ADRs in web-based questionnaires as useful and not burdensome. It was preferred to link the questionnaire frequency to regular hospital consultations or the biologic administration schedule. Various respondents were interested in sharing questionnaires with their medical specialist (49.0%) or pharmacist (34.2%), and suggested to minimize the questionnaire frequency in case of an unaltered situation or absence of ADRs.

Conclusions: Patients' perspectives should be considered in the setup of PRO-based CEM studies, as this contributes to data quality and patient centeredness. Since incorporation of patients' perspectives in CEM studies is indispensable, a delicate balance should be found between user-friendliness and study aims.
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http://dx.doi.org/10.1080/14740338.2021.1963436DOI Listing
August 2021

Re-induction with intravenous Ustekinumab after secondary loss of response is a valid optimization strategy in Crohn's disease.

Eur J Gastroenterol Hepatol 2021 Jul 30. Epub 2021 Jul 30.

Department of Gastroenterology and Hepatology, Erasmus MC, Rotterdam Radboudumc, Nijmegen Maastricht UMC, Maastricht Department of Gastroenterology, Amsterdam UMC, VU University Medical Center, AG and M Research Institute, Amsterdam Department of Gastroenterology and Hepatology, Franciscus Gasthuis and Vlietland, Rotterdam, The Netherlands.

Background And Aim: Re-induction with intravenous ustekinumab after secondary loss of response in Crohn's disease is a relatively new strategy to regain efficacy. This real-world cohort study aimed to evaluate its effectiveness and safety.

Methods: Crohn's disease patients with loss of response after initial response to ustekinumab and treated with a second intravenous dose of ustekinumab were included. Clinical, biochemical and endoscopic data were collected. Primary outcome was drug survival. Secondary effectiveness outcomes included clinical remission, primary nonresponse and adverse events.

Results: In total, 31 Crohn's disease patients were included after re-induction with intravenous ustekinumab. All patients had failed prior biologic therapy, that is 77% were exposed to two or more antitumor necrosis factor agents and 65% were exposed to vedolizumab prior to initiation of ustekinumab treatment. Median treatment duration between initial treatment and re-induction with intravenous ustekinumab was 11.1 months (interquartile range 6.9-19.5). Ustekinumab therapy after a second dose of intravenous ustekinumab was maintained in 74 and 71% of the patients at weeks 20 and 52. Clinical remission rates after re-induction at weeks 8, 20 and 52 were 37, 56 and 45%, respectively. Nonresponse occurred in 16% of the patients. Adverse events were reported in four patients.

Conclusions: Re-induction with intravenous ustekinumab after secondary loss of response results in continuation of ustekinumab treatment for at least 1 year in almost three-quarters of patients and in clinical remission in half of patients after 1 year. Therefore, ustekinumab re-induction may be considered an important rescue treatment option in patients with refractory Crohn's disease.
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http://dx.doi.org/10.1097/MEG.0000000000002256DOI Listing
July 2021

Letter: tofacitinib in treatment-refractory ulcerative colitis-a single centre real-world experience in Australia. Authors' reply.

Aliment Pharmacol Ther 2021 08;54(4):534-535

Gastroenterology and Hepatology, Maastricht Universitair Medisch Centrum+, Maastricht, The Netherlands.

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http://dx.doi.org/10.1111/apt.16505DOI Listing
August 2021

Pharmacokinetic-Pharmacodynamic Model of Vedolizumab for Targeting Endoscopic Remission in Patients With Crohn Disease: Posthoc Analysis of the LOVE-CD Study.

Inflamm Bowel Dis 2021 Jun 17. Epub 2021 Jun 17.

Department of Hospital Pharmacy-Clinical Pharmacology, Amsterdam UMC, Amsterdam, the Netherlands.

Background: Higher serum concentrations of vedolizumab have been associated with improved outcomes in inflammatory bowel disease. It is unclear how vedolizumab exposure is linked to endoscopic remission in Crohn disease (CD). We aimed to develop a pharmacokinetic-pharmacodynamic model linking vedolizumab exposure to endoscopic remission in CD.

Methods: Data were obtained from the first 110 patients participating in a phase 4 prospective multicenter trial (LOVE-CD; ClinicalTrials.gov identifier: NCT02646683), where vedolizumab was dosed at 300 mg every 8 weeks and serum concentrations and antibodies to vedolizumab were measured before each infusion. Concentration-time profiles were described by a 2-compartment model with parallel linear and nonlinear elimination. A first-order discrete-time Markov model was used to describe the relationship between pharmacokinetic exposure metrics and the probability of endoscopic remission (Simple Endoscopic Score for CD < 4).

Results: Linear clearance was 0.215 L/d, and the volume of distribution of the central compartment was 4.92 L. Linear clearance was higher and vedolizumab exposure was lower in patients with lower serum albumin concentrations, in the presence of antibodies to vedolizumab, and in patients with previous exposure to other biologic therapy. A week 22 vedolizumab concentration of 20.0 mg/L was predicted to yield a 35% probability of achieving endoscopic remission at week 26. Model-based simulations suggested that endoscopic remission rates of 46.5% or 40.0% could be reached with every-4-weeks dosing in patients who were naïve or previously exposed to biologic therapy, respectively.

Conclusions: Model-informed dosing of vedolizumab in CD provides a foundation for future research aiming to maximize endoscopic remission rates.
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http://dx.doi.org/10.1093/ibd/izab143DOI Listing
June 2021

Pregnancy and neonatal outcomes in women with immune mediated inflammatory diseases exposed to anti-tumor necrosis factor-α during pregnancy: A systemic review and meta-analysis.

J Autoimmun 2021 Aug 11;122:102676. Epub 2021 Jun 11.

Laboratory of Medical Immunology, Department of Laboratory Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands. Electronic address:

Background: Anti-TNFα is increasingly used as treatment for immune mediated inflammatory diseases (IMID), such as inflammatory bowel disease (IBD), rheumatoid arthritis (RA) and psoriasis (PS). However, the impact of anti-TNFα during pregnancy on mother and newborn is under debate. This requires a sound knowledge of the effects of this treatment on pregnancy and neonatal outcomes.

Objectives: To assess pregnancy and neonatal outcomes after anti-TNFα therapy during pregnancy in women with IMID, specifically IBD, RA and PS.

Methods: We performed a systematic review and meta-analysis of 39 studies assessing pregnancy and neonatal outcomes of women with IMID exposed to anti-TNFα agents during pregnancy. We used a random-effects model to determine pooled outcome measures.

Results: An increased risk of preterm births (OR 1.45, 95% CI = 1.16 to 1.82, p = 0.001) and infections in newborns (OR 1.12, 95% CI = 1.00 to 1.27, p = 0.05)) was seen for women in the combined group of IMID exposed to anti-TNFα compared to diseased controls. Specifically for IBD patients exposed to anti-TNFα, the risk was increased for preterm birth (OR 1.66, 95% CI = 1.14 to 2.42, p = 0.009), and low birth weight (OR 1.49, 95% CI = 1.01 to 2.20, p = 0.047) compared to diseased controls. Combined data from studies of women with RA and PS, showed no increased risk for adverse pregnancy outcome after exposure to anti-TNFα. Most children of mothers with IMID received vaccination according to national vaccination schemes and only minor adverse events were reported.

Conclusion: Exposure to anti-TNFα agents during pregnancy is associated with increased risk of preterm birth and infections in newborns of women with IMID compared to diseased controls. The risk of preterm birth and low birth weight was increased in women with IBD specifically. The increased risk of infections in newborns underlines the importance of vaccination, which seems to be safe in children exposed to anti-TNFα. Delay of vaccination is therefore unnecessary in these children. These data may aid in balancing the continuing anti-TNFα therapy versus the risk of adverse pregnancy outcomes.
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http://dx.doi.org/10.1016/j.jaut.2021.102676DOI Listing
August 2021

Discrepancy between patient- and healthcare provider-reported adverse drug reactions in inflammatory bowel disease patients on biological therapy.

United European Gastroenterol J 2021 Oct 2;9(8):919-928. Epub 2021 Jun 2.

Department of Gastroenterology and Hepatology, Radboud University Medical Centre, Nijmegen, The Netherlands.

Background: Only limited data is available on the extent and burden of adverse drug reactions (ADRs) to biological therapy in inflammatory bowel disease (IBD) patients in daily practice, especially from a patient's perspective.

Objective: The aim of this study was to systematically assess patient-reported ADRs during biological therapy in IBD patients and compare these with healthcare provider (HCP)-reported ADRs.

Methods: This multicentre, prospective, event monitoring study enrolled IBD patients on biological therapy. Patients completed bimonthly comprehensive web-based questionnaires regarding description of biological induced ADRs, follow-up of previous ADRs and experienced burden of the ADR using a five-point Likert scale. The relationship between patient-reported ADRs and biological therapy was assessed. HCP-reported ADRs were extracted from the electronic healthcare records.

Results: In total, 182 patients (female 51%, mean age 42.2 [standard deviation 14.2] years, Crohn's disease 77%) were included and completed 728 questionnaires. At baseline, 60% of patients used infliximab, 30% adalimumab, 9% vedolizumab and 1% ustekinumab. Fifty percent of participants reported at least one ADR with a total of 239 unique ADRs. Fatigue (n = 26) and headache (n = 20) resulted in the highest burden and a correlation in time with the administration of the biological was described in 56% and 85% respectively. Out of 239 ADRs, 115 were considered biological-related. HCPs reported 119 ADRs. Agreement between patient-reported ADRs and HCP-reported ADRs was only 13%.

Conclusion: IBD patients often report ADRs during biological therapy. We observed an important significant difference between the type and frequency of patient-reported ADRs versus HCP-reported ADRs, leading to an underestimation of more subjective ADRs and patients' ADR-related burden.
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http://dx.doi.org/10.1002/ueg2.12107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8498403PMC
October 2021

Gastrointestinal Adverse Drug Reaction Profile of Etanercept: Real-world Data From Patients and Healthcare Professionals.

J Rheumatol 2021 Sep 15;48(9):1388-1394. Epub 2021 May 15.

H.E. Vonkeman, MD, PhD, Department of Psychology, Health & Technology, University of Twente, and Department of Rheumatology and Clinical Immunology, Medisch Spectrum Twente, Enschede, the Netherlands.

Objective: We aimed to describe the nature and frequency of gastrointestinal adverse drug reactions (GI-ADRs) of etanercept (ETN) using patient-reported and healthcare professional (HCP)-registered data and compared this frequency with the GI-ADR frequency of the widely used tumor necrosis factor-α inhibitor adalimumab (ADA).

Methods: Reported GI-ADRs of ETN for rheumatic diseases were collected from the Dutch Biologic Monitor and DREAM registries. We described the clinical course of GI-ADRs and compared the frequency with ADA in both data sources using Fisher exact test.

Results: Out of 416 patients using ETN for inflammatory rheumatic diseases in the Dutch Biologic Monitor, 25 (6%) patients reported 36 GI-ADRs. In the DREAM registries 11 GI-ADRs were registered for 9 patients (2.3%), out of 399 patients using ETN, with an incidence of 7.1 per 1000 patient-years. Most GI-ADRs consisted of diarrhea, nausea, and abdominal pain. GI-ADRs led to ETN discontinuation in 1 patient (4%) and dose adjustment in 4 (16%) in the Dutch Biologic Monitor. Eight GI-ADRs (73%) led to ETN discontinuation in the DREAM registries. The frequency of GI-ADRs of ETN did not significantly differ from GI-ADRs of ADA in both data sources (Dutch Biologic Monitor: ETN 8.7% vs ADA 5.3%, = 0.07; DREAM: ETN 2.8% vs ADA 4.7%, = 0.16).

Conclusion: Most GI-ADRs associated with ETN concerned gastrointestinal symptoms. These ADRs may lead to dose adjustment or ETN discontinuation. The frequency of ETN-associated GI-ADRs was comparable to the frequency of ADA-associated GI-ADRs. Knowledge about these previously unknown ADRs can facilitate early recognition and improve patient communication.
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http://dx.doi.org/10.3899/jrheum.201373DOI Listing
September 2021

WSES-AAST guidelines: management of inflammatory bowel disease in the emergency setting.

World J Emerg Surg 2021 05 11;16(1):23. Epub 2021 May 11.

Department of Surgical Sciences, Policlinico Sant'Orsola Malpighi, Bologna, Italy.

Background: Despite the current therapeutic options for the treatment of inflammatory bowel disease, surgery is still frequently required in the emergency setting, although the number of cases performed seems to have decreased in recent years. The World Society of Emergency Surgery decided to debate in a consensus conference of experts, the main pertinent issues around the management of inflammatory bowel disease in the emergent situation, with the need to provide focused guidelines for acute care and emergency surgeons.

Method: A group of experienced surgeons and gastroenterologists were nominated to develop the topics assigned and answer the questions addressed by the Steering Committee of the project. Each expert followed a precise analysis and grading of the studies selected for review. Statements and recommendations were discussed and voted at the Consensus Conference of the 6th World Society of Emergency Surgery held in Nijmegen (The Netherlands) in June 2019.

Conclusions: Complicated inflammatory bowel disease requires a multidisciplinary approach because of the complexity of this patient group and disease spectrum in the emergency setting, with the aim of obtaining safe surgery with good functional outcomes and a decreasing stoma rate where appropriate.
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http://dx.doi.org/10.1186/s13017-021-00362-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111988PMC
May 2021

Ustekinumab for Crohn's Disease: Two-Year Results of the Initiative on Crohn and Colitis (ICC) Registry, a Nationwide Prospective Observational Cohort Study.

J Crohns Colitis 2021 Apr 28. Epub 2021 Apr 28.

Leiden University Medical Centre, Department of Gastroenterology and Hepatology, Leiden, The Netherlands.

Objective: Ustekinumab is a monoclonal antibody that selectively targets p40, a shared subunit of the cytokines interleukin (IL)-12 and IL-23. It is registered for the treatment of inflammatory bowel diseases. We assessed the two-year effectiveness and safety of ustekinumab in a real world, prospective cohort of patients with Crohn's disease (CD).

Methods: Patients who started ustekinumab were prospectively enrolled in the nationwide Initiative on Crohn and Colitis (ICC) Registry. At week 0, 12, 24, 52 and 104, clinical remission (HBI ≤ 4 points), biochemical remission (fecal calprotectin (FC) ≤200 μg/g and/or CRP ≤5 mg/L), peri-anal fistula remission, extra-intestinal manifestations, ustekinumab dosage and safety outcomes were determined. The primary outcome was corticosteroid-free clinical remission at week 104.

Results: In total, 252 CD patient with at least two years of follow up were included. Of all included patients, the proportion of patients in corticosteroid-free clinical remission was 32.3% (81/251), 41.4% (104/251), 39% (97/249) and 34.0% (84/247), at week 12, 24, 52 and 104, respectively. In patients with combined clinical and biochemical disease activity at baseline (n=122), the corticosteroid-free clinical remission rates were 23.8% (29/122), 35.2% (43/122), 40.0% (48/120) and 32.8% (39/119) at week 12, 24, 52 and 104, respectively. The probability of remaining on ustekinumab treatment after 52 and 104 weeks in all patients was 64.3% and 54.8%, respectively. The main reason for discontinuing treatment after 52 weeks was loss of response (66.7%). No new safety issues were observed.

Conclusion: After 104 weeks of ustekinumab treatment, one third of CD patients were in corticosteroid-free clinical remission.
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http://dx.doi.org/10.1093/ecco-jcc/jjab081DOI Listing
April 2021

Adverse Drug Reactions from Real-World Data in Inflammatory Bowel Disease Patients in the IBDREAM Registry.

Drug Saf 2021 May 4;44(5):581-588. Epub 2021 Feb 4.

Department of Gastroenterology and Hepatology, Radboud University Medical Centre, Nijmegen, The Netherlands.

Introduction: Inflammatory bowel disease (IBD) frequently requires chronic immunosuppressive treatment and active involvement from patients during treatment decision making. Information about the risk of developing adverse drug reactions (ADRs) to IBD therapies is required in this process.

Objective: The aim of this study was to describe the ADRs reported in IBD patients from real-world data, using the Dutch nationwide IBDREAM registry, and compare the occurrence and cumulative incidences with the Summary of Product Characteristics (SmPC) of the associated drugs.

Methods: In this retrospective multicentre study, ADRs related to IBD medication were assessed. Only reports associated with the use of drugs used for the maintenance treatment of IBD were included. All ADRs were verified by healthcare professionals and coded by trained pharmacovigilance assessors.

Results: In total, 3080 ADRs were reported in 1179 patients. Twenty-three new drug-ADR associations related to the use of azathioprine, mercaptopurine, infliximab, oral mesalamine and thioguanine were reported in the IBDREAM registry that were not mentioned in the corresponding SmPCs. The most frequently reported new association was pyrexia for azathioprine (3.1%) and mercaptopurine (4.9%). In addition, there were seven ADRs with a higher cumulative incidence in IBDREAM compared with the SmPC, and included, among others, arthralgia during mercaptopurine use (2.5%), and diarrhoea (1.4%), alopecia (1.2%) and infections (1.6%) during azathioprine use.

Conclusions: Based on real-world data, ADR reporting demonstrated new ADRs and higher incidences of ADRs to IBD therapies. This information will contribute to drug safety by updating the SmPCs, allowing better risk assessment and communication towards patients.
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http://dx.doi.org/10.1007/s40264-021-01045-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053178PMC
May 2021

Outcome of Reverse Switching From CT-P13 to Originator Infliximab in Patients With Inflammatory Bowel Disease.

Inflamm Bowel Dis 2021 Feb 4. Epub 2021 Feb 4.

Department of Gastroenterology and Hepatology, University Medical Centre Utrecht, Utrecht, the Netherlands.

Background: Patients suffering from inflammatory bowel diseases (IBD) and treated with originator infliximab are increasingly being switched to biosimilars. Some patients, however, are "reverse switched" to treatment with the originator. Here we assess the prevalence of reverse switching, including its indication and outcomes.

Methods: In this retrospective multicenter cohort study, data on patients with IBD from 9 hospitals in the Netherlands were collected. All adult patients with IBD were included if they previously had been switched from originator infliximab to the biosimilar CT-P13 and had a follow-up time of at least 52 weeks after the initial switch. The reasons for reverse switching were categorized into worsening gastrointestinal symptoms, adverse effects, or loss of response to CT-P13. Drug persistence was analyzed through survival analyses.

Results: A total of 758 patients with IBD were identified. Reverse switching was observed in 75 patients (9.9%). Patients with reverse switching were predominantly female (70.7%). Gastrointestinal symptoms (25.5%) and dermatological symptoms (21.8%) were the most commonly reported reasons for reverse switching. In 9 patients (12.0%), loss of response to CT-P13 was the reason for reverse switching. Improvement of reported symptoms was seen in 73.3% of patients after reverse switching and 7 out of 9 patients (77.8%) with loss of response regained response. Infliximab persistence was equal between patients who were reverse-switched and those who were maintained on CT-P13.

Conclusions: Reverse switching occurred in 9.9% of patients, predominantly for biosimilar-attributed adverse effects. Switching back to originator infliximab seems effective in patients who experience adverse effects, worsening gastrointestinal symptoms, or loss of response after switching from originator infliximab to CT-P13.
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http://dx.doi.org/10.1093/ibd/izaa364DOI Listing
February 2021

Healthy Cotwins Share Gut Microbiome Signatures With Their Inflammatory Bowel Disease Twins and Unrelated Patients.

Gastroenterology 2021 05 19;160(6):1970-1985. Epub 2021 Jan 19.

Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. Electronic address:

Background & Aims: It is currently unclear whether reported changes in the gut microbiome are cause or consequence of inflammatory bowel disease (IBD). Therefore, we studied the gut microbiome of IBD-discordant and -concordant twin pairs, which offers the unique opportunity to assess individuals at increased risk of developing IBD, namely healthy cotwins from IBD-discordant twin pairs.

Methods: Fecal samples were obtained from 99 twins (belonging to 51 twin pairs), 495 healthy age-, sex-, and body mass index-matched controls, and 99 unrelated patients with IBD. Whole-genome metagenomic shotgun sequencing was performed. Taxonomic and functional (pathways) composition was compared among healthy cotwins, IBD-twins, unrelated patients with IBD, and healthy controls with multivariable (ie, adjusted for potential confounding) generalized linear models.

Results: No significant differences were observed in the relative abundance of species and pathways between healthy cotwins and their IBD-twins (false discovery rate <0.10). Compared with healthy controls, 13, 19, and 18 species, and 78, 105, and 153 pathways were found to be differentially abundant in healthy cotwins, IBD-twins, and unrelated patients with IBD, respectively (false discovery rate <0.10). Of these, 8 (42.1%) of 19 and 1 (5.6%) of 18 species, and 37 (35.2%) of 105 and 30 (19.6%) of 153 pathways overlapped between healthy cotwins and IBD-twins, and healthy cotwins and unrelated patients with IBD, respectively. Many of the shared species and pathways have previously been associated with IBD. The shared pathways include potentially inflammation-related pathways, for example, an increase in propionate degradation and L-arginine degradation pathways.

Conclusions: The gut microbiome of healthy cotwins from IBD-discordant twin pairs displays IBD-like signatures. These IBD-like microbiome signatures might precede the onset of IBD. However, longitudinal follow-up studies are needed to infer a causal relationship.
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http://dx.doi.org/10.1053/j.gastro.2021.01.030DOI Listing
May 2021

Prognostic Factors for Advanced Colorectal Neoplasia in Inflammatory Bowel Disease: Systematic Review and Meta-analysis.

Gastroenterology 2021 04 29;160(5):1584-1598. Epub 2020 Dec 29.

Inflammatory Bowel Disease Centre, Department of Gastroenterology and Hepatology, University Medical Centre Utrecht, Utrecht, the Netherlands. Electronic address:

Background And Aims: Patients with inflammatory bowel disease (IBD) have an increased risk of colorectal cancer (CRC). We performed a systematic review and meta-analysis to identify all prognostic factors for advanced colorectal neoplasia (aCRN, high-grade dysplasia, or CRC) in patients with IBD.

Methods: A systematic literature search was conducted according to the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. Risk of bias was assessed using the Quality in Prognostic Studies tool. Random-effects models were created separately for odds and hazard ratios, different study designs, and univariable or multivariable data. The evidence for all prognostic factors was categorized as "weak", "moderate", or "strong", based on estimate of effect sizes, heterogeneity, and risk of bias.

Results: A total of 164 studies were included, allowing pooled analysis of 31 potential prognostic factors. In the univariable analysis, the evidence for extensive disease was classified as strong while evidence for low-grade dysplasia, strictures, primary sclerosing cholangitis, post-inflammatory polyps, family history of CRC, and ulcerative colitis versus Crohn's disease was considered moderate. Evidence for any dysplasia, colon segment resection, aneuploidy, male sex, and age was classified as weak. In addition, histologic inflammation was identified as a risk factor in multivariable analysis (weak evidence). The evidence for the protective factors colonoscopic surveillance, 5-Aminosalicylic Acid, thiopurines, and smoking was moderate in univariable analysis. Multivariable analysis provided weak evidence for statin use.

Conclusions: In this systematic review and meta-analysis, we identified 13 risk factors and 5 protective factors for aCRN in IBD patients, based on univariable and/or multivariable pooled analyses. These findings might lay the groundwork for an improved CRC risk stratification-based surveillance in IBD.
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http://dx.doi.org/10.1053/j.gastro.2020.12.036DOI Listing
April 2021

Cross-cultural translation and validation of the IBD-control questionnaire in The Netherlands: a patient-reported outcome measure in inflammatory bowel disease.

Scand J Gastroenterol 2021 Feb 10;56(2):155-161. Epub 2020 Dec 10.

Department of Gastroenterology and Hepatology, Medical Spectrum Twente, Enschede, The Netherlands.

Background: There is a need for easy-to-use patient-reported outcome measures (PROMS) in inflammatory bowel disease (IBD) practice. The 'IBD-control' is a short IBD-specific questionnaire capturing disease control from the patient's perspective. The International Consortium for Health Outcomes Measurement (ICHOM) recommends the use of the IBD-control even though it has only been validated in the United Kingdom. We aimed to cross-culturally translate and validate the IBD-control in the Netherlands using IBDREAM, a prospective multicentre IBD registry.

Methods: Lack of ambiguity and acceptability were verified in a pilot patient group ( = 5) after forward-backward translation of the IBD-control. Prospective validation involved completion of the IBD-control, Short Form-36, short IBDQ and disease activity measurement by Physician Global Assessment (PGA) and Simple Clinical Colitis Activity Index or Harvey-Bradshaw Index. Test-retest (2-week repeat) was used for measuring reliability.

Results: Questionnaires were completed by 998 IBD patients (674 Crohn's disease, 324 ulcerative colitis). Internal consistency (Cronbach's alpha) was 0.82 for the sub-group of 8 questions (IBD-control-8-sub-score). Mean completion time was 105 s. Construct validity analyses demonstrated moderate-to-strong correlations of the IBD-control-8-subscore and the other instruments (0.49-0.81). Test-retest reliability for stable patients was high (intraclass correlation coefficient 0.95). The IBD-control-8-subscore showed good discriminant ability between the PGA categories (ANOVA, <.001). Sensitivity to change analyses showed large effect sizes of 0.81-1.87 for the IBD-control-8 subscore.

Conclusions: These results support the IBD-control as a rapid, reliable, valid and sensitive instrument for measuring disease control from an IBD patient's perspective in the Netherlands.
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http://dx.doi.org/10.1080/00365521.2020.1857430DOI Listing
February 2021

Inflammatory bowel disease patients provide reliable self-reported medical information: A multicentre prospective pharmacovigilance monitoring system.

Pharmacoepidemiol Drug Saf 2021 04 1;30(4):520-524. Epub 2020 Dec 1.

Department of Gastroenterology and Hepatology, Radboud University Medical Centre, Nijmegen, The Netherlands.

Purpose: To assess the agreement between patient-reported and health care provider-reported medical information in inflammatory bowel disease (IBD).

Methods: This multicentre, prospective, event monitoring study enrolled adult Crohn's disease (CD) and ulcerative colitis (UC) patients treated with a biological in four medical centers in the Netherlands. At two-monthly intervals, patients completed questionnaires on biological use, combination therapy and indication. The patient-reported information was compared with their electronic health records (EHRs) and analysed for percentage agreement and Cohen's kappa. A reference population from a prospective IBD registry was used to assess the representativeness of the study population.

Results: In total, 182 patients (female 50.5%, mean age 42.2 years, CD 76.9%) were included in the analysis. At baseline, 51.0% of the patients were prescribed an immunomodulator (43.9% thiopurines, 7.1% methotrexate), and patients were prescribed biologicals as follows: 59.3% infliximab, 30.2% adalimumab, 9.3% vedolizumab, and 1.1% ustekinumab. Agreement on patient-reported indication and biological use was almost perfect (κ = 0.878 and κ = 1.000, respectively); substantial for combination therapy (κ = 0.672). Gender, age, type of IBD, biological use and combination therapy were comparable with the reference population.

Conclusion: Systematic patient-reporting by questionnaires was reliable in retrieving indication and treatment specific information from IBD patients. These results indicate that the use of patient-reporting outcomes in daily IBD practice can ensure reliable information collection.
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http://dx.doi.org/10.1002/pds.5175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7983909PMC
April 2021

Reduction in Inflammatory Bowel Disease Healthcare During the Coronavirus Disease 2019 Pandemic: A Nationwide Retrospective Cohort Study.

Gastroenterology 2021 02 22;160(3):935-937.e1. Epub 2020 Oct 22.

Inflammatory Bowel Disease Center, Department of Gastroenterology, Radboud University Medical Center, Nijmegen, The Netherlands.

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http://dx.doi.org/10.1053/j.gastro.2020.10.032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581342PMC
February 2021

Editorial: is age just a number when it comes to treatment of inflammatory bowel disease? Authors' reply.

Aliment Pharmacol Ther 2020 11;52(10):1617-1618

Leiden University Medical Centre, Leiden, The Netherlands.

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http://dx.doi.org/10.1111/apt.16106DOI Listing
November 2020

Clinical Outcomes of Covid-19 in Patients With Inflammatory Bowel Disease: A Nationwide Cohort Study.

J Crohns Colitis 2021 Apr;15(4):529-539

Department of Gastroenterology and Hepatology, Radboud University Medical Centre, Nijmegen, The Netherlands.

Background And Aims: The COVID-19 risk and disease course in inflammatory bowel disease [IBD] patients remains uncertain. Therefore, we aimed to assess the clinical presentation, disease course, and outcomes of COVID-19 in IBD patients. Second, we determined COVID-19 incidences in IBD patients and compared this with the general population.

Methods: We conducted a multicentre, nationwide IBD cohort study in The Netherlands and identified patients with COVID-19. First, we assessed the COVID-19 disease course and outcomes. Second, we compared COVID-19 incidences between our IBD study cohort and the general Dutch population.

Results: We established an IBD cohort of 34 763 patients. COVID-19 was diagnosed in 100/34 763 patients [0.29%]; 20/100 of these patients [20%] had severe COVID-19 defined as admission to the intensive care unit, mechanical ventilation, and/or death. Hospitalisation occurred in 59/100 [59.0%] patients and 13/100 [13.0%] died. All patients who died had comorbidities and all but one were ≥65 years old. In line, we identified ≥1 comorbidity as an independent risk factor for hospitalisation (odds ratio [OR] 4.20, 95% confidence interval [CI] 1.58-11.17,; p = 0.004). Incidences of COVID-19 between the IBD study cohort and the general population were comparable (287.6 [95% CI 236.6-349.7] versus 333.0 [95% CI 329.3-336.7] per 100000 patients, respectively; p = 0.15).

Conclusions: Of 100 cases with IBD and COVID-19, 20% developed severe COVID-19, 59% were hospitalised and 13% died. A comparable COVID-19 risk was found between the IBD cohort [100/34 763 = 0.29%] and the general Dutch population. The presence of ≥1 comorbidities was an independent risk factor for hospitalisation due to COVID-19.
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http://dx.doi.org/10.1093/ecco-jcc/jjaa215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665430PMC
April 2021

Health outcomes of 1000 children born to mothers with inflammatory bowel disease in their first 5 years of life.

Gut 2021 Jul 12;70(7):1266-1274. Epub 2020 Oct 12.

Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, The Netherlands.

Objective: The aim of this study was to describe the long-term health outcomes of children born to mothers with inflammatory bowel disease (IBD) and to assess the impact of maternal IBD medication use on these outcomes.

Design: We performed a multicentre retrospective study in The Netherlands. Women with IBD who gave birth between 1999 and 2018 were enrolled from 20 participating hospitals. Information regarding disease characteristics, medication use, lifestyle, pregnancy outcomes and long-term health outcomes of children was retrieved from mothers and medical charts. After consent of both parents, outcomes until 5 years were also collected from general practitioners. Our primary aim was to assess infection rate and our secondary aims were to assess adverse reactions to vaccinations, growth, autoimmune diseases and malignancies.

Results: We included 1000 children born to 626 mothers (381 (61%) Crohn's disease, 225 (36%) ulcerative colitis and 20 (3%) IBD unclassified). In total, 196 (20%) had intrauterine exposure to anti-tumour necrosis factor-α (anti-TNF-α) (60 with concomitant thiopurine) and 240 (24%) were exposed to thiopurine monotherapy. The 564 children (56%) not exposed to anti-TNF-α and/or thiopurine served as control group. There was no association between adverse long-term health outcomes and in utero exposure to IBD treatment. We did find an increased rate of intrahepatic cholestasis of pregnancy (ICP) in case thiopurine was used during the pregnancy without affecting birth outcomes and long-term health outcomes of children. All outcomes correspond with the general age-adjusted population.

Conclusion: In our study, we found no association between in utero exposure to anti-TNF-α and/or thiopurine and the long-term outcomes antibiotic-treated infections, severe infections needing hospital admission, adverse reactions to vaccinations, growth failure, autoimmune diseases and malignancies.
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http://dx.doi.org/10.1136/gutjnl-2019-319129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223671PMC
July 2021

Letter: effectiveness of ustekinumab or vedolizumab in Crohn's disease following anti-TNF failure-getting closer to the truth. Authors' reply.

Aliment Pharmacol Ther 2020 10;52(7):1255-1256

Maastricht University Medical Centre, Maastricht, the Netherlands.

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http://dx.doi.org/10.1111/apt.16062DOI Listing
October 2020

Clinical management of the most common extra-intestinal manifestations in patients with inflammatory bowel disease focused on the joints, skin and eyes.

United European Gastroenterol J 2020 11 14;8(9):1031-1044. Epub 2020 Sep 14.

Department of Medicine, Division of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands.

Extra-intestinal manifestations (EIMs) of inflammatory bowel disease (IBD) occur frequently and contribute to morbidity and reduced quality of life. The musculoskeletal, ocular and cutaneous organ systems are frequently involved in IBD-related EIMs. By focusing on manifestations involving the joints, skin and eyes, this review will discuss the most common clinically relevant and burdensome EIMs that affect IBD patients, and strives for early recognition, adequate treatment and timely referral. For this purpose, we aimed to create a comprehensive overview on this topic, with the main focus on the treatment of reactive and associated EIMs, including spondyloarthropathies, pyoderma gangrenosum, erythema nodosum, psoriasis and anterior uveitis. The recently developed biologicals enable simultaneous treatment of inflammatory disorders. This review can be used as a helpful guide in daily clinical practice for physicians who are involved in the treatment of IBD patients.
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http://dx.doi.org/10.1177/2050640620958902DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724540PMC
November 2020

Comorbidity, not patient age, is associated with impaired safety outcomes in vedolizumab- and ustekinumab-treated patients with inflammatory bowel disease-a prospective multicentre cohort study.

Aliment Pharmacol Ther 2020 10 9;52(8):1366-1376. Epub 2020 Sep 9.

Leiden, the Netherlands.

Background: Few data are available on the effects of age and comorbidity on treatment outcomes of vedolizumab and ustekinumab in inflammatory bowel disease (IBD).

Aims: To evaluate the association between age and comorbidity with safety and effectiveness outcomes of vedolizumab and ustekinumab in IBD.

Methods: IBD patients initiating vedolizumab or ustekinumab in regular care were enrolled prospectively. Comorbidity prevalence was assessed using the Charlson Comorbidity Index (CCI). Association between age and CCI, both continuously assessed, with safety outcomes (any infection, hospitalisation, adverse events) during treatment, and effectiveness outcomes (clinical response and remission, corticosteroid-free remission, clinical remission combined with biochemical remission) after 52 weeks of treatment were evaluated. Multivariable logistic regression was used to adjust for confounders.

Results: We included 203 vedolizumab- and 207 ustekinumab-treated IBD patients, mean age 42.2 (SD 16.0) and 41.6 (SD 14.4). Median treatment duration 54.0 (IQR 19.9-104.0) and 48.4 (IQR 24.4-55.1) weeks, median follow-up time 104.0 (IQR 103.1-104.0) and 52.0 weeks (IQR 49.3-100.4). On vedolizumab, CCI associated independently with any infection (OR 1.387, 95% CI 1.022-1.883, P = 0.036) and hospitalisation (OR 1.586, 95% CI 1.127-2.231, P = 0.008). On ustekinumab, CCI associated independently with hospitalisation (OR 1.621, 95% CI 1.034-2.541, P = 0.035). CCI was not associated with effectiveness, and age was not associated with any outcomes.

Conclusions: Comorbidity - but not age - is associated with an increased risk of hospitalisations on either treatment, and with any infection on vedolizumab. This underlines the importance of comorbidity assessment and safety monitoring of IBD patients.
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http://dx.doi.org/10.1111/apt.16073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539998PMC
October 2020

Letter: ustekinumab's effectiveness compared with vedolizumab in Crohn's disease-what about mucosal healing and biomarkers? Authors' reply.

Aliment Pharmacol Ther 2020 08;52(4):753-754

Maastricht University Medical Centre, Maastricht, the Netherlands.

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http://dx.doi.org/10.1111/apt.15959DOI Listing
August 2020

Stakeholders' perspectives on a patient-reported outcome measure-based drug safety monitoring system for immune-mediated inflammatory diseases.

Expert Opin Drug Saf 2020 Nov 12;19(11):1521-1528. Epub 2020 Aug 12.

Institute for Computing and Information Sciences, Radboud University , Nijmegen, The Netherlands.

Background: Biologics are used as effective therapeutics to treat a variety of diseases. Even though biologics are widely used, knowledge on the post-marketing experience of patients is limited. Therefore, a framework was established for a patient-reported outcome measure (PROM)-based drug safety monitoring system for ADRs attributed to biologics, known as the 'Dutch Biologic Monitor'.

Objective: Generation of a multi-stakeholder perspective on the preferred setup, potential and added value of a PROM-based national drug safety monitoring system.

Methods: Nineteen stakeholders were interviewed following a structured interview guide. Transcribed data were coded and analyzed to count frequencies and to generate recurring themes.

Results: Stakeholders (84.2%) support the establishment of a national drug safety monitoring system, but the feasibility depends on the implementation process. The need for integration and assessment of PROMs on ADRs in clinical practice and the preference to monitor small molecules and new drugs were emphasized. Preferably, all pharmacological options per indication should be monitored.

Conclusions: Stakeholders recommend to establish a PROM-based national drug safety monitoring system focused on ADRs attributed to biologics, small molecules, and new drugs. Moreover, PROMs on ADRs ideally need to become integrated in clinical practice to provide health-care providers more insight in patients' perspectives.
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http://dx.doi.org/10.1080/14740338.2020.1803826DOI Listing
November 2020

Immediate Infusion Reaction to Intravenous Ustekinumab in Three Crohn's Disease Patients: A Case Report and Review of the Literature.

J Crohns Colitis 2021 Jan;15(1):162-164

Department of Gastroenterology and Hepatology, Radboud University Medical Centre, Nijmegen, The Netherlands.

Recently, ustekinumab has been approved for the treatment of Crohn's disease and ulcerative colitis. Treatment is started with an intravenous induction dose, followed by a subcutaneous dosage. We present details of three patients with therapy-refractory Crohn's disease who experienced an immediate infusion reaction to intravenous administration of ustekinumab. In two of these patients a subsequent reaction to subcutaneous injections occurred. Clinical features and pathophysiology are discussed.
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http://dx.doi.org/10.1093/ecco-jcc/jjaa115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805788PMC
January 2021

Immune-mediated inflammatory disease patients' preferences in adverse drug reaction information regarding biologics.

Expert Opin Drug Saf 2020 Aug 7;19(8):1049-1054. Epub 2020 Jul 7.

Netherlands Pharmacovigilance Centre Lareb , 's-Hertogenbosch, The Netherlands.

Objectives: Patient-reported outcomes (PROs) are increasingly used in studies and medical practice to obtain information on patients' perspectives toward their treatment or disease. However, most study outcomes are primarily directed at healthcare professionals. It was aimed to obtain insight in which type of information immune-mediated inflammatory disease (IMID) patients prefer to receive after participating in the Dutch Biologic Monitor (DBM), a PRO-based prospective cohort event monitoring system focused on adverse drug reactions (ADRs).

Methods: A survey was conducted among DBM participants that wanted information about the results. Patients' preferences were identified using twelve statements and rated with five-point Likert-type scales. Subgroup analyses and differences between statements were performed using Mann-Whitney U Tests.

Results: The survey was completed by 591 patients (response rate 67.6%). Most respondents had inflammatory rheumatic diseases (76.8%) and used adalimumab (37.2%) or etanercept (33.2%). Respondents preferred results per IMID over aggregated results (p = <0.001). Information on whether patients with similar IMIDs experience ADRs (average 4.5), which biologics are most likely to cause ADRs (4.4) and whether ADRs disappear (4.4) were most interesting.

Conclusion: DBM participants prefer to receive disease-specific information on ADRs that is tailored to their own biologic and IMID, including the outcome of ADRs.
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http://dx.doi.org/10.1080/14740338.2020.1781090DOI Listing
August 2020

High-Dose Vitamin D Does Not Prevent Postoperative Recurrence of Crohn's Disease in a Randomized Placebo-Controlled Trial.

Clin Gastroenterol Hepatol 2021 08 24;19(8):1573-1582.e5. Epub 2020 May 24.

Department of Gastroenterology and Hepatology. Electronic address:

Background & Aims: Vitamin D deficiency is common in Crohn's disease (CD). High-dose vitamin D had anti-inflammatory effects in preclinical studies and trials of patients with CD. We performed a randomized trial to determine whether high-dose vitamin D prevents postoperative recurrence of CD after ileocolonic resection.

Methods: Patients with CD after ileocolonic resection with ileocolonic anastomosis were assigned randomly to groups given weekly 25,000 IU oral vitamin D (n = 72) or placebo (n = 71) for 26 weeks, at 17 hospitals in The Netherlands and Belgium, from February 2014 through June 2017. Patients were assessed at baseline and at weeks 2, 6, 12, and 26 for laboratory and clinical parameters, and underwent ileocolonoscopy at 26 weeks. The primary end point was endoscopic recurrence (modified Rutgeerts score, ≥i2b, as assessed by blinded readers) at 26 weeks. Secondary end points included clinical recurrence (Crohn's disease activity index, ≥220), quality of life (measured by the 36-Item Short Form Health Survey, Inflammatory Bowel Disease Questionnaire, and EuroQol, a 5-dimension questionnaire), and outcomes associated with the baseline serum concentration of vitamin D.

Results: In the vitamin D group, serum levels of 25-hydroxy vitamin D increased from a median of 42 nmol/L at baseline to 81 nmol/L at week 26 (P < .00001), whereas levels did not change significantly in the placebo group and remained unchanged at 43 nmol/L. In the intention-to-treat analysis, the proportion of patients with endoscopic recurrence at 26 weeks did not differ significantly between the vitamin D vs the placebo group (58% vs 66%; P = .37). The cumulative rate of clinical recurrence did not differ significantly between the groups (18.1% in the vitamin D group vs 18.3% in the placebo group; P = .91). Quality of life improved slightly over time in both groups, but did not differ significantly between groups (P = .07). There were few adverse events in either group.

Conclusions: High-dose vitamin D, compared with placebo, did not reduce the incidence of postoperative endoscopic or clinical recurrence of CD in patients who underwent ileocolonic resection with ileocolonic anastomosis. ClinicalTrials.gov no: NCT02010762.
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http://dx.doi.org/10.1016/j.cgh.2020.05.037DOI Listing
August 2021

Patient-Reported Burden of Adverse Drug Reactions Attributed to Biologics Used for Immune-Mediated Inflammatory Diseases.

Drug Saf 2020 09;43(9):917-925

Department of Pharmacy, Sint Maartenskliniek, Nijmegen, The Netherlands.

Introduction: Although the burden of adverse drug reactions (ADRs) has a significant impact on patients' quality of life, thorough knowledge about patients' perspectives on the burden of ADRs attributed to biologics is lacking.

Objectives: This study was conducted to gain insight into the patient burden of ADRs experienced with biologic use.

Methods: The Dutch Biologic Monitor is a prospective, multicentre, event monitoring cohort system including information collected by web-based questionnaires from patients using biologics, mainly for immune-mediated inflammatory diseases (IMIDs). Patients were asked to complete bimonthly questionnaires on biologics used, indication for the biologic, experienced ADRs, consequences of ADRs and burden on a five-point Likert-type scale, ranging from 1 (no burden) to 5 (very high burden). We assessed potential factors associated with patient-reported burden of ADRs.

Results: A total of 1355 patients completed 6293 questionnaires between 1 January 2017 and 1 May 2019. Almost half of the patients (665 patients, 49%), 69% with rheumatic diseases and 31% with other diseases, collectively reported 1720 unique ADRs. Infections and musculoskeletal complaints were the most burdensome ADRs and injection-site reactions were the least burdensome. ADRs leading to healthcare professional contact were more burdensome than ADRs without healthcare professional contact. Smoking, respiratory and psychiatric comorbidities were associated with higher burden of ADRs. Crohn's disease, use of adalimumab and use of sulfasalazine as combination therapy were associated with lower burden of ADRs.

Conclusions: The patient perspective gives important insights into the burden of ADRs experienced with biologics. This information could be used by healthcare professionals to optimise treatment with biologics.
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http://dx.doi.org/10.1007/s40264-020-00946-zDOI Listing
September 2020

Ustekinumab is associated with superior effectiveness outcomes compared to vedolizumab in Crohn's disease patients with prior failure to anti-TNF treatment.

Aliment Pharmacol Ther 2020 07 22;52(1):123-134. Epub 2020 May 22.

Maastricht, the Netherlands.

Background: Both vedolizumab and ustekinumab can be considered for the treatment of Crohn's disease (CD) when anti-TNF treatment fails. However, head-to-head trials are currently not available or planned.

Aim: To compare vedolizumab and ustekinumab in Crohn´s disease patients in a prospective registry specifically developed for comparative studies with correction for confounders.

Methods: Crohn´s disease patients, who failed anti-TNF treatment and started vedolizumab or ustekinumab in standard care as second-line biological, were identified in the observational prospective Dutch Initiative on Crohn and Colitis Registry. Corticosteroid-free clinical remission (Harvey Bradshaw Index ≤4), biochemical remission (C-reactive protein ≤5 mg/L and fecal calprotectin ≤250 µg/g), combined corticosteroid-free clinical and biochemical remission, and safety outcomes were compared after 52 weeks of treatment. To adjust for confounding and selection bias, we used multiple logistic regression and propensity score matching.

Results: In total, 128 vedolizumab- and 85 ustekinumab-treated patients fulfilled the inclusion criteria. After adjusting for confounders, ustekinumab-treated patients were more likely to achieve corticosteroid-free clinical remission (odds ratio [OR]: 2.58, 95% CI: 1.36-4.90, P = 0.004), biochemical remission (OR: 2.34, 95% CI: 1.10-4.96, P = 0.027), and combined corticosteroid-free clinical and biochemical remission (OR: 2.74, 95% CI: 1.23-6.09, P = 0.014), while safety outcomes (infections: OR: 1.26, 95% CI: 0.63-2.54, P = 0.517; adverse events: OR: 1.33, 95% CI: 0.62-2.81, P = 0.464; hospitalisations: OR: 0.67, 95% CI: 0.32-1.39, P = 0.282) were comparable between the two groups. The propensity score matched cohort with sensitivity analyses showed comparable results.

Conclusions: Ustekinumab was associated with superior effectiveness outcomes when compared to vedolizumab, while safety outcomes were comparable after 52 weeks of treatment in CD patients who have failed anti-TNF treatment.
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http://dx.doi.org/10.1111/apt.15745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7318204PMC
July 2020
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