Publications by authors named "Mark Lowenberg"

Article Synopsis
  • Standardized evaluation of endoscopic disease activity is essential for effective clinical trials targeting Crohn's disease (CD) since achieving endoscopic remission improves long-term patient outcomes.
  • Various endoscopic indices have been developed, with CDEIS and SES-CD showing decent reliability, but they have limitations such as complexity, time consumption, and variability.
  • The SES-CD is recommended for use in future trials because it's simpler and correlates well with the more complex CDEIS, and further research is needed to define endoscopic response and remission cutoff values.
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The aviation sector needs to work fast to address its impact on the environment. A small conference in Bristol brought together technologists, climate scientists, policy makers and activists to examine the issues. Here we report on presentations and discussions from the conference, exploring insights, innovations and policy implications critical for significant climate impact mitigation within this decisive decade.

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Article Synopsis
  • The study evaluated the cost-effectiveness of therapeutic drug monitoring (TDM)-guided mercaptopurine treatment for ulcerative colitis (UC) patients who didn’t respond to traditional medication compared to a placebo.
  • Data was collected from a controlled trial and analyzed over one year, considering various costs related to healthcare and societal impacts.
  • Results suggested that while mercaptopurine had slightly higher costs per additional patient achieving remission, it provided significant societal cost savings and had an 80% chance of being cost-effective within a specific budget for healthcare spending.
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Background & Aims: Vedolizumab is indicated for the treatment of chronic pouchitis in the European Union. We assessed whether vedolizumab induced mucosal healing (MH) and if MH was associated with clinical improvements.

Methods: EARNEST, a randomized, double-blind, placebo-controlled study, evaluated vedolizumab efficacy and safety in adults with chronic pouchitis.

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Article Synopsis
  • The study explores how patients on immunosuppressants (ISPs) respond to SARS-CoV-2 infections compared to healthy controls, particularly looking at antibody levels post-infection.
  • Patients with immune-mediated inflammatory diseases (IMIDs) on different ISP therapies showed variable antibody responses, with those on anti-CD20 and sphingosine-1 phosphate therapies having lower antibody levels.
  • Despite lower antibody titers, the breakthrough infections in these patients were mostly mild, indicating that ISPs may not severely impede the overall immune response to SARS-CoV-2.
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Background And Aims: Histological outcomes and JAK-STAT signalling were assessed in a prospective ulcerative colitis [UC] patient cohort after 8 weeks treatment with tofacitinib, an oral Janus kinase [JAK] inhibitor.

Methods: Forty UC patients received tofacitinib 10 mg twice daily for 8 weeks. Treatment response was defined as histo-endoscopic mucosal improvement [HEMI].

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Subcutaneous vedolizumab has demonstrated efficacy as a maintenance therapy in inflammatory bowel disease (IBD). However, data on the extension of subcutaneous vedolizumab injection intervals are lacking. Here, we present the first real-world data on subcutaneous vedolizumab interval extension in IBD patients.

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Article Synopsis
  • SARS-CoV-2-specific CD8 T cells play a crucial role in protecting against viral variants and reducing disease severity, especially in patients lacking cross-reactive antibodies.
  • mRNA vaccines elicit strong immune responses, but the effectiveness among patients with chronic immune-mediated inflammatory disorders (IMIDs), particularly those on TNF inhibitors (TNFi), is less understood.
  • Analysis revealed that both TNFi-treated and untreated inflammatory bowel disease (IBD) patients generate strong spike-specific CD8 T cell responses after mRNA vaccination, comparable to healthy individuals, indicating that vaccination is beneficial regardless of treatment status.
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This paper describes the implementation of inflammatory bowel disease (IBD)-specific cognitive behavioural therapy (CBT) for IBD patients with poor quality of life (QoL), anxiety and depression, in four hospitals in the Netherlands. Treatment outcomes were compared with those of a previously published randomized control trial (RCT) of 'IBD-specific CBT', following a benchmark strategy. Primary outcome was IBD-specific QoL (IBDQ) completed before and after CBT, secondary outcomes were anxiety and depressive symptoms (HADS, CES-D).

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We present a Crohn's disease patient receiving high dose upadacitinib treatment with elevated CPK levels and myopathy, and provide the reader with practical tips on stopping and restarting upadacitinib, emphasizing the need for adequate monitoring.

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Background: STARDUST, a phase 3b randomised trial, compared ustekinumab therapeutic strategies in patients with Crohn's disease (CD) using early endoscopic assessment and treat-to-target (T2T) versus standard of care (SoC).

Aim: To assess the efficacy of ustekinumab extended treatment in a long-term extension (LTE) of up to 104 weeks with dosing adapted according to clinical, biomarker and endoscopy outcomes.

Methods: Adults with moderately-to-severely active CD received intravenous ustekinumab approximating 6 mg/kg at Week 0 and subcutaneous ustekinumab 90 mg at Week 8.

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Background And Aims: We explored the potential for differential efficacy of vedolizumab between early and late ulcerative colitis [UC] with evaluation of clinical, endoscopic, and histological endpoints.

Methods: This was a multicentre, multinational, open-label study in patients with moderately-to-severely active UC, defining early UC by a disease duration <4 years and bio-naïve and late UC by a disease duration > 4 years and additional exposure to tumour necrosis factor antagonists. Patients received standard treatment with intravenous vedolizumab for 52 weeks [300 mg Weeks 0, 2, 6, every 8 weeks thereafter without escalation].

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Background And Aims: Crohn's disease [CD] is a debilitating, inflammatory condition affecting the gastrointestinal tract. There is no cure and sustained clinical and endoscopic remission is achieved by fewer than half of patients with current therapies. The immunoregulatory function of the vagus nerve, the 'inflammatory reflex', has been established in patients with rheumatoid arthritis and biologic-naive CD.

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Introduction: Predictive biomarkers for treatment efficacy of ulcerative colitis [UC] treatments are lacking. Here, we performed a longitudinal study investigating the association and potential predictive power of genome-wide peripheral blood [PB] DNA methylation signatures and response to tofacitinib treatment in UC.

Methods: We recruited moderate-to-severe UC patients starting tofacitinib treatment, and measured PB DNA methylation profiles at baseline [T1], after 8 weeks [T2], and in a subset [n = 8] after a median of 20 weeks [T3] using the Illumina Infinium HumanMethylation EPIC BeadChip.

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Article Synopsis
  • A study was conducted to evaluate a new point-of-care test (POCT) device that measures inflammation markers and drug levels in patients with inflammatory bowel disease (IBD) by comparing it to standard reference methods.
  • The study involved 285 patients and focused on testing infliximab (IFX), adalimumab (ADL), C-reactive protein (CRP), and fecal calprotectin (FCP) levels using various blood and stool samples.
  • Results indicated that the POCT showed good agreement with reference methods, with some slight discrepancies; IFX and ADL levels were higher in POCT, while CRP and FCP levels were lower, suggesting the POCT is effective but may require further
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Background: Patients with immune-mediated inflammatory diseases (IMIDs) on immunosuppressants (ISPs) may have impaired long-term humoral immune responses and increased disease activity after SARS-CoV-2 infection. We aimed to investigate long-term humoral immune responses against SARS-CoV-2 and increased disease activity after a primary SARS-CoV-2 infection in unvaccinated IMID patients on ISPs.

Methods: IMID patients on active treatment with ISPs and controls (i.

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Background: Approximately half the patients with ulcerative colitis who undergo restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) will subsequently have pouchitis, and among those patients, one fifth will have chronic pouchitis.

Methods: We conducted a phase 4, double-blind, randomized trial to evaluate vedolizumab in adult patients in whom chronic pouchitis had developed after undergoing IPAA for ulcerative colitis. Patients were assigned (in a 1:1 ratio) to receive vedolizumab intravenously at a dose of 300 mg or placebo on day 1 and at weeks 2, 6, 14, 22, and 30.

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Background And Aims: Scepticism about the efficacy of thiopurines for ulcerative colitis [UC] is rising. This study aimed to evaluate mercaptopurine treatment for UC.

Methods: In this prospective, randomized, double-blind, placebo-controlled trial, patients with active UC, despite treatment with 5-aminosalicylates [5-ASA], were randomized for therapeutic drug monitoring [TDM]-guided mercaptopurine treatment or placebo for 52 weeks.

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For patients with immune-mediated inflammatory diseases (IMIDs), concerns exist about increased disease activity after vaccination. We aimed to assess changes in disease activity after SARS-CoV-2 vaccination in patients with IMIDs, and determine risk factors for increased disease activity. In this substudy of a prospective observational cohort study (Target-to-B!), we included patients with IMIDs who received a SARS-CoV-2 vaccine.

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Objectives: To compare the cumulative incidence and disease severity of reported SARS-CoV-2 omicron breakthrough infections between patients with immune-mediated inflammatory diseases (IMID) on immunosuppressants and controls, and to investigate determinants for breakthrough infections.

Methods: Data were used from an ongoing national prospective multicentre cohort study on SARS-CoV-2 vaccination responses in patients with IMID in the Netherlands (Target-to-B! (T2B!) study). Patients wih IMID on immunosuppressants and controls (patients with IMID not on immunosuppressants and healthy controls) who completed primary immunisation were included.

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Background: Tofacitinib is an oral Janus kinase (JAK) inhibitor and is registered for the treatment of ulcerative colitis (UC). The effectiveness of tofacitinib has been evaluated up to 12 months of treatment.

Aim: The aim of this study was to assess the effectiveness and safety of 24 months of tofacitinib use in UC patients in the Netherlands.

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Background And Aims: There is a need to evaluate the benefit-risk ratio of current therapies in inflammatory bowel disease (IBD) patients to provide the best quality of care. The primary objective of I-CARE (IBD Cancer and serious infections in Europe) was to assess prospectively safety concerns in IBD, with specific focus on the risk of cancer/lymphoma and serious infections in patients treated with anti-tumor necrosis factor and other biologic monotherapy as well as in combination with immunomodulators.

Methods: I-CARE was designed as a European prospective longitudinal observational multicenter cohort study to include patients with a diagnosis of Crohn's disease, ulcerative colitis, or IBD unclassified established at least 3 months prior to enrollment.

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Background & Aims: Intestinal ultrasound (IUS) is noninvasive, cost-effective, and accurate to determine disease activity in ulcerative colitis (UC). In this study, we prospectively evaluated IUS for treatment response in a longitudinal cohort by using endoscopy and histology as gold standards.

Methods: Consecutive patients with moderate to severe UC (endoscopic Mayo score [EMS] ≥2) starting tofacitinib treatment were included.

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