Publications of Edouard Louis
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See detailEditorial: Personalizing Treatment in IBD: Hype or Reality in 2020?
Gomollón, Fernando; Louis, Edouard ULiege

in Frontiers in Medicine (2021), 8

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See detailTofacitinib De-escalation Strategy in Ulcerative Colitis: Is It the End of the Story?
Guillo, Lucas; Peyrin-Biroulet, Laurent; Louis, Edouard ULiege

in Journal of Crohn's & colitis (2021), 15(7), 1087-1088

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See detailQuality of Life and Work Productivity Improvements with Upadacitinib: Phase 2b Evidence from Patients with Moderate to Severe Crohn’s Disease
Peyrin-Biroulet, L.; Louis, Edouard ULiege; Loftus, E. V. et al

in Advances in Therapy (2021)

Introduction: In the phase 2 CELEST study, positive efficacy results were obtained with the Janus kinase 1 inhibitor upadacitinib for adult patients with moderate to severe Crohn’s disease. We present the ... [more ▼]

Introduction: In the phase 2 CELEST study, positive efficacy results were obtained with the Janus kinase 1 inhibitor upadacitinib for adult patients with moderate to severe Crohn’s disease. We present the health-related quality of life and work productivity improvement results with upadacitinib from CELEST. Methods: CELEST (NCT02365649) was a double-blind study where patients were randomized 1:1:1:1:1:1 in the 16-week induction period to placebo or upadacitinib 3 mg twice daily (BID), 6 mg BID, 12 mg BID, 24 mg BID, or 24 mg once daily (QD). Patients completing the induction period were re-randomized 1:1:1 to receive upadacitinib 3 mg BID, 12 mg BID, or 24 mg QD for 36 weeks or 3 mg BID, 6 mg BID, or 12 mg BID (after amendment). Inflammatory Bowel Disease Questionnaire (IBDQ), European Quality of Life-5 Dimensions visual analog scale (EQ-5D VAS), and Work Productivity and Activity Impairment (WPAI) questionnaire outcomes were assessed at baseline and Weeks 8, 16, and 52. Results: At Week 16, a significant percentage (P ≤ 0.05) of patients receiving upadacitinib 6-mg BID dose or higher achieved IBDQ response (IBDQ score change ≥ 16 points; 49%–57% for upadacitinib vs. 24% for placebo) and IBDQ remission, except 24 mg QD (IBDQ score ≥ 170; 26%–39% for upadacitinib vs. 11% for placebo). Greater improvements in IBDQ total score, EQ-5D VAS, and activity impairment from baseline (P ≤ 0.1) versus placebo were also observed. Larger improvements (P ≤ 0.1) in IBDQ response and total score and EQ-5D VAS were observed at Week 8 with 6 and 24 mg BID versus placebo, with improvements for all dosages maintained or greater at Week 52 for IBDQ, EQ-5D VAS, and WPAI endpoints, in particular for the 12-mg BID group. Conclusion: Improvements in health-related quality of life and work productivity were achieved and sustained with upadacitinib in patients with moderate to severe Crohn’s disease. Trial Registration: ClinicalTrials.gov identifier, NCT02365649. © 2021, The Author(s). [less ▲]

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See detailReview article: distinctions between ileal and colonic Crohn's disease: from physiology to pathology.
Pierre, Nicolas ULiege; Salée, Catherine; Vieujean, Sophie et al

in Alimentary pharmacology & therapeutics (2021), 54(6), 779-791

BACKGROUND: Ileal and colonic Crohn's disease seem to be two separate entities. AIMS: To describe the main physiological distinctions between the small and the large intestine and to analyse the ... [more ▼]

BACKGROUND: Ileal and colonic Crohn's disease seem to be two separate entities. AIMS: To describe the main physiological distinctions between the small and the large intestine and to analyse the differences between ileal and colonic Crohn's disease. METHODS: The relevant literature was critically examined and synthesised. RESULTS: The small and large intestine have fundamental distinctions (anatomy, cellular populations, immune defence, microbiota). The differences between ileal and colonic Crohn's disease are highlighted by a heterogeneous body of evidence including clinical features (natural history of the disease, efficacy of treatments, and monitoring), epidemiological data (smoking status, age, gender) and biological data (genetics, microbiota, immunity, mesenteric fat). However, the contribution of these factors to disease location remains poorly understood. CONCLUSION: The classification of ileal and colonic Crohn's disease as distinct subphenotypes is well supported by the literature. Understanding of these differences could be exploited to develop more individualised patient care. [less ▲]

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See detailPerspectives From Patients and Gastroenterologists on De-escalating Therapy for Crohn's Disease
Siegel, Corey A.; Thompson, Kimberly D.; Walls, Danielle et al

in Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association (2021)

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See detailEfficacy of anti-TNF dosing interval lengthening in adolescents and young adults with inflammatory bowel disease in sustained remission (FREE-study): protocol for a partially randomised patient preference trial.
Bouhuys, Marleen; Lexmond, Willem S.; Dijkstra, Gerard et al

in BMJ Open (2021), 11(11), 054154

INTRODUCTION: Anti-tumour necrosis factor (TNF) therapy has greatly improved treatment outcomes in patients with inflammatory bowel disease (IBD), but long-term use is associated with cutaneous reactions ... [more ▼]

INTRODUCTION: Anti-tumour necrosis factor (TNF) therapy has greatly improved treatment outcomes in patients with inflammatory bowel disease (IBD), but long-term use is associated with cutaneous reactions, susceptibility to infections and frequent injections or hospital visits. Several non-controlled studies have demonstrated that dose reduction is feasible for a subset of patients, provided that early detection of a disease flare is possible. Here, we aim to compare the effectiveness of interval lengthening with standard dosing in maintaining remission in young patients with IBD. METHODS AND ANALYSIS: In this international, prospective, non-inferiority, partially randomised patient preference trial, we aim to recruit 148 patients aged 12-25 years with luminal Crohn's disease or ulcerative colitis in sustained remission (ie, three consecutive in-range faecal calprotectin (FC) results or recently confirmed endoscopic remission). In the interventional arm, the dosing interval will be lengthened from 8 to 12 weeks for infliximab users and from 2 to 3 weeks for adalimumab users. In the control group, standard dosing will be continued. Rapid tests will be performed for FC every 4 weeks and for anti-TNF trough levels every 12 weeks. The primary outcome is the cumulative incidence of out-of-range FC results at 48-week follow-up. Secondary endpoints include time to get out-of-range FC results, cumulative incidence of adverse effects, proportion of patients progressing to loss of response and identification of predictors of successful interval lengthening. ETHICS AND DISSEMINATION: The protocol has been approved by the Medical Ethics Review Committee of the University Medical Centre Groningen and is pending at the other participating centres. Results will be disseminated in peer-reviewed journals and presented at scientific meetings. TRIAL REGISTRATION NUMBER: EudraCT number: 2020-001811-26; ClinicalTrials.gov Identifier: NCT04646187. Protocol version 4, date 17 September 2021. [less ▲]

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See detailAssociation of IgG1 Antibody Clearance with FcγRIIA Polymorphism and Platelet Count in Infliximab-Treated Patients.
Thibault, Gilles; Paintaud, Gilles; Sung, Hsueh Cheng et al

in International journal of molecular sciences (2021), 22(11),

The FcγRIIA/CD32A is mainly expressed on platelets, myeloid and several endothelial cells. Its affinity is considered insufficient for allowing significant binding of monomeric IgG, while its H131R ... [more ▼]

The FcγRIIA/CD32A is mainly expressed on platelets, myeloid and several endothelial cells. Its affinity is considered insufficient for allowing significant binding of monomeric IgG, while its H131R polymorphism (histidine > arginine at position 131) influences affinity for multimeric IgG2. Platelet FcγRIIA has been reported to contribute to IgG-containing immune-complexe clearance. Given our finding that platelet FcγRIIA actually binds monomeric IgG, we investigated the role of platelets and FcγRIIA in IgG antibody elimination. We used pharmacokinetics analysis of infliximab (IgG1) in individuals with controlled Crohn's disease. The influence of platelet count and FcγRIIA polymorphism was quantified by multivariate linear modelling. The infliximab half-life increased with R allele number (13.2, 14.4 and 15.6 days for HH, HR and RR patients, respectively). It decreased with increasing platelet count in R carriers: from ≈20 days (RR) and ≈17 days (HR) at 150 × 10(9)/L, respectively, to ≈13 days (both HR and RR) at 350 × 10(9)/L. Moreover, a flow cytometry assay showed that infliximab and monomeric IgG1 bound efficiently to platelet FcγRIIA H and R allotypes, whereas panitumumab and IgG2 bound poorly to the latter. We propose that infliximab (and presumably any IgG1 antibody) elimination is partly due to an unappreciated mechanism dependent on binding to platelet FcγRIIA, which is probably tuned by its affinity for IgG2. [less ▲]

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See detailUpadacitinib Treatment Improves Symptoms of Bowel Urgency and Abdominal Pain, and Correlates With Quality of Life Improvements in Patients With Moderate to Severe Ulcerative Colitis.
Ghosh, Subrata; Sanchez Gonzalez, Yuri; Zhou, Wen et al

in Journal of Crohn's & colitis (2021)

BACKGROUND AND AIMS: Bowel urgency and abdominal pain are impactful, yet underappreciated ulcerative colitis symptoms and not commonly assessed in clinical trials. We evaluated how these symptoms may ... [more ▼]

BACKGROUND AND AIMS: Bowel urgency and abdominal pain are impactful, yet underappreciated ulcerative colitis symptoms and not commonly assessed in clinical trials. We evaluated how these symptoms may improve with upadacitinib treatment and correlate with clinical and health-related quality of life (HRQOL) outcomes in the phase 2b U-ACHIEVE study. METHODS: Patients aged 18-75 years with moderately to severely active ulcerative colitis were randomised to receive placebo or upadacitinib (7.5, 15, 30, or 45 mg QD). Bowel urgency and abdominal pain were evaluated at baseline and Weeks 2, 4, 6, and 8. Week 8 correlations were evaluated between bowel urgency/abdominal pain with clinical (Mayo subscores, and high-sensitivity C-reactive protein and faecal calprotectin measurements) and HRQOL outcomes (Inflammatory Bowel Disease Questionnaire and 36-Item Short Form Health Survey scores). RESULTS: A greater proportion of patients (N = 250) reported no bowel urgency and less abdominal pain with upadacitinib treatment compared to placebo, with improvements observed as early as 2 weeks. At Week 8, patients receiving the 45-mg QD dose had the greatest improvements versus placebo, with 46% reporting no bowel urgency (vs 9%; P ≤0.001) and 38% reporting no abdominal pain (vs 13%; P = 0.015). At Week 8, moderate correlations were found between bowel urgency or abdominal pain and most clinical and HRQOL outcomes. CONCLUSIONS: Induction treatment with upadacitinib demonstrated significant reductions in bowel urgency and abdominal pain compared to placebo. These symptoms also correlate to clinical and HRQOL outcomes, supporting their use to monitor disease severity and other treatment outcomes. [less ▲]

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See detailSARS-CoV-2 vaccination for patients with inflammatory bowel diseases: recommendations from an international consensus meeting.
Siegel, Corey A.; Melmed, Gil Y.; McGovern, Dermot Pb et al

in Gut (2021), 70(4), 635-640

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See detailLong-Term Safety and Efficacy of Risankizumab Treatment in Patients with Crohn's Disease: Results from the Phase 2 Open-Label Extension Study.
Ferrante, Marc; Feagan, Brian G.; Panés, Julián et al

in Journal of Crohn's & colitis (2021)

BACKGROUND AND AIMS: Risankizumab, an interleukin-23 antibody, demonstrated efficacy and acceptable safety in a phase 2 study of patients with moderate-to-severe refractory Crohn's disease. This open ... [more ▼]

BACKGROUND AND AIMS: Risankizumab, an interleukin-23 antibody, demonstrated efficacy and acceptable safety in a phase 2 study of patients with moderate-to-severe refractory Crohn's disease. This open-label extension investigated the long-term safety, pharmacokinetics, immunogenicity, and efficacy of risankizumab in responders to risankizumab in the parent phase 2 study. METHODS: Enrolled patients had achieved clinical response (decrease in Crohn's Disease Activity Index from baseline ≥100) without clinical remission (Crohn's Disease Activity Index <150) at Week 26, or clinical response and/or remission at Week 52 in the parent phase 2 study and received open-label subcutaneous risankizumab 180 mg every 8 weeks. RESULTS: Sixty-five patients were enrolled, including 4 patients who had lost response in the parent study and were first reinduced with risankizumab 600 mg every 4 weeks (three infusions). Patients received risankizumab for a median of 33 months (total: 167.0 patient-years). The rate of serious adverse events was 24.6 events/100 patient-years; the majority were gastrointestinal in nature. Rates of serious infections, opportunistic infections, and fungal infections were 4.2, 1.8, and 6.6 events/100 patient-years, respectively. No deaths, malignancies, adjudicated major adverse cardiovascular events, latent/active tuberculosis, or herpes zoster were reported. Treatment-emergent anti-drug antibodies developed in 8 patients (12.3%); none were neutralising. Efficacy outcomes were maintained during the study, including the proportions of patients (observed analysis) with clinical remission (>71%) and endoscopic remission (>42%). CONCLUSIONS: Long-term maintenance treatment with subcutaneous risankizumab 180 mg every 8 weeks was well tolerated by patients with Crohn's disease, with no new safety signals. [less ▲]

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See detailLong-Term Safety and Efficacy of the Anti-Mucosal Addressin Cell Adhesion Molecule-1 Monoclonal Antibody Ontamalimab (SHP647) for the Treatment of Crohn's Disease: The OPERA II Study.
D'Haens, Geert R.; Reinisch, Walter; Lee, Scott D. et al

in Inflammatory Bowel Diseases (2021)

BACKGROUND: Patients with Crohn's disease (CD) experience intestinal inflammation. Ontamalimab (SHP647), a fully human immunoglobulin G2 monoclonal antibody against mucosal addressin cell adhesion ... [more ▼]

BACKGROUND: Patients with Crohn's disease (CD) experience intestinal inflammation. Ontamalimab (SHP647), a fully human immunoglobulin G2 monoclonal antibody against mucosal addressin cell adhesion molecule-1, is a potential novel CD treatment. OPERA II, a multicenter, open-label, phase 2 extension study, assessed the long-term safety and efficacy of ontamalimab in patients with moderate-to-severe CD. METHODS: Patients had completed 12 weeks of blinded treatment (placebo or ontamalimab at 22.5, 75, or 225 mg subcutaneously) in OPERA (NCT01276509) or had a clinical response to ontamalimab 225 mg in TOSCA (NCT01387594). Participants received ontamalimab at 75 mg every 4 weeks (weeks 0-72), then were followed up every 4 weeks for 24 weeks. One-time dose reduction to 22.5 mg or escalation to 225 mg was permitted at the investigator's discretion. The primary end points were safety and tolerability outcomes. Secondary end points included changes in serum drug and biomarker concentrations. Efficacy end points were exploratory, and used non-responder imputation methods. RESULTS: Overall, 149/268 patients completed the study. The most common adverse event leading to study discontinuation was CD flare (19.8%). Two patients died; neither death was considered to be drug related. No dose reductions occurred; 157 patients had their dose escalated. Inflammatory biomarker concentrations decreased. Serum ontamalimab levels were consistent with known pharmacokinetics. Remission rates (Harvey-Bradshaw Index [HBI] ≤ 5; baseline, 48.1%; week 72, 37.3%) and response rates (baseline [decrease in Crohn's Disease Activity Index ≥ 70 points], 63.1%; week 72 [decrease in HBI ≥ 3], 42.5%) decreased gradually. CONCLUSIONS: Ontamalimab was well tolerated; treatment responses appeared to be sustained over 72 weeks.ClinicalTrials.gov ID: NCT01298492. [less ▲]

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See detailInternational consensus on methodological issues in standardization of fecal calprotectin measurement in inflammatory bowel diseases.
D'Amico, Ferdinando; Rubin, David T.; Kotze, Paulo Gustavo et al

in United European Gastroenterology Journal (2021), 9(4), 451-460

BACKGROUND: Fecal calprotectin (FC) is a non-invasive marker of gut inflammation which is frequently used to guide therapeutic decisions in patients with inflammatory bowel diseases (IBD). Each step of FC ... [more ▼]

BACKGROUND: Fecal calprotectin (FC) is a non-invasive marker of gut inflammation which is frequently used to guide therapeutic decisions in patients with inflammatory bowel diseases (IBD). Each step of FC measurement can influence the results, leading to misinterpretations and potentially impacting the management of IBD patients. To date, there is high heterogeneity between FC measurements and no current method is universally accepted as a standard. AIMS: Our aim was to provide clear position statementsabout the pre-analytical and the analytical phases of FC measurement to homogenize FC levels and to minimize variability and risk of misinterpretation through aninternational consensus. MATERIALS & METHODS: Fourteen physicians with expertise in the field of IBD and FC from 11 countries attended a virtual international consensus meeting on July 17th, 2020. A systematic literature was conducted and the literature evidence was shared and discussedamong the participants. Statements were formulated, discussed, and voted. Statements were considered approved if all participants agreed. RESULTS: Nine statements were formulated and approved. Based on the available evidence, quantitative tests should be preferred for measuring FC. Furthermore, FC measurement, if possible, should always be performed with the same method and factors influencing FC levels should be taken into account when interpreting the results. DISCUSSION: FC has an increasingly important role in the management of patients with IBD. However, large multicenter studies should be conducted to define the reproducibility and to confirm the diagnostic accuracy of the available FC tests. CONCLUSION: FC concentrations guide clinicians' treatment decisions. Our statements have a relevant impact in daily practice and could be applied in clinical trials to standardize FC measurement. [less ▲]

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See detailDeterminants of IBD-related disability: a cross-sectional survey from the GETAID.
Tannoury, Jenny; Nachury, Maria; Martins, Carole et al

in Alimentary pharmacology & therapeutics (2021), 53(10), 1098-1107

BACKGROUND: The burden of inflammatory bowel disease (IBD) is rising worldwide. The goal of IBD treatment is to achieve clinical and endoscopic remission but also prevent disability. AIMS: To identify the ... [more ▼]

BACKGROUND: The burden of inflammatory bowel disease (IBD) is rising worldwide. The goal of IBD treatment is to achieve clinical and endoscopic remission but also prevent disability. AIMS: To identify the predictive factors of disability in a large population of patients with IBD. PATIENTS AND METHODS: We conducted a cross-sectional survey in 42 tertiary centres in France and Belgium. A self-administered questionnaire was designed to explore patients and their IBD characteristics. IBD-disk is a validated tool to measure disability in patients with IBD. The IBD-disk score was then calculated for each patient. Based on a previous study, an overall IBD-disk score ≥40 was associated with moderate-to-severe disability. RESULTS: Among the 2011 patients, 1700 were analysed, including 746 (44%) in self-reported clinical remission and 752 (44.2%) declaring clinical activity. The patient global assessment of global remission was missing in 200 (11.8%) of 1700 patients. Moderate-to-severe disability was significantly increased in patients with BMI >25 kg/m(2) (OR = 1.66; 95% CI [1.29-2.14]), in those having perception of need for a psychotherapist (OR = 2.24; 95% CI [1.79-3.05]) and social worker (OR = 1.54; 95% CI [1.08-2.21]). Conversely, male gender (OR = 0.83; 95% CI [0.69-0.99]), ulcerative colitis (OR = 0.69; 95% CI [0.53-0.92]), self-reported clinical remission (OR = 0.59; 95% CI [0.46-0.77]) and employed or student occupational status (OR = 0.69; 95% CI [0.52-0.92]) were inversely correlated with disability. Overall, 257 (34.5%) patients who declared being in clinical remission had disability. CONCLUSION: Determinants of IBD-related disability include IBD-related factors but also psychological and social factors. This highlights the importance of a multidisciplinary team in the management of patients with IBD. [less ▲]

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See detailMapping the human genetic architecture of COVID-19 by worldwide meta-analysis
The COVID-19 Host Genetics Initiative; Gazon, Hélène; JUSZCZAK, Danusia ULiege et al

in Nature (2021)

The genetic makeup of an individual contributes to susceptibility and response to viral infection. While environmental, clinical and social factors play a role in exposure to SARS-CoV-2 and COVID-19 ... [more ▼]

The genetic makeup of an individual contributes to susceptibility and response to viral infection. While environmental, clinical and social factors play a role in exposure to SARS-CoV-2 and COVID-19 disease severity, host genetics may also be important. Identifying host-specific genetic factors indicate biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-COV-2 infection and COVID-19 severity. We describe the results of three genome-wide association meta-analyses comprising 49,562 COVID-19 patients from 46 studies across 19 countries worldwide. We reported 15 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases. They also represent potentially actionable mechanisms in response to infection. We further identified smoking and body mass index as causal risk factors for severe COVID-19. The identification of novel host genetic factors associated with COVID-19, with unprecedented speed, was enabled by prioritization of shared resources and analytical frameworks. This working model of international collaboration a blue-print for future genetic discoveries in the event of pandemics or for any complex human disease. [less ▲]

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See detailInternational consensus on the prevention of venous and arterial thrombotic events in patients with inflammatory bowel disease.
Olivera, Pablo A.; Zuily, Stephane; Kotze, Paulo G. et al

in Nature Reviews Gastroenterology and Hepatology (2021), 18(12), 857-873

Patients with inflammatory bowel disease (IBD) are at increased risk of thrombotic events. Therapies for IBD have the potential to modulate this risk. The aims of this Evidence-Based Guideline were to ... [more ▼]

Patients with inflammatory bowel disease (IBD) are at increased risk of thrombotic events. Therapies for IBD have the potential to modulate this risk. The aims of this Evidence-Based Guideline were to summarize available evidence and to provide practical recommendations regarding epidemiological aspects, prevention and drug-related risks of venous and arterial thrombotic events in patients with IBD. A virtual meeting took place in May 2020 involving 14 international IBD experts and 3 thrombosis experts from 12 countries. Proposed statements were voted upon in an anonymous manner. Agreement was defined as at least 75% of participants voting as 'fully agree' or 'mostly agree' with each statement. For each statement, the level of evidence was graded according to the Scottish Intercollegiate Guidelines Network (SIGN) grading system. Consensus was reached for 19 statements. Patients with IBD harbour an increased risk of venous and arterial thrombotic events. Thromboprophylaxis is indicated during hospitalization of any cause in patients with IBD. Disease activity is a modifiable risk factor in patients with IBD, and physicians should aim to achieve deep remission to reduce the risk. Exposure to steroids should be limited. Antitumour necrosis factor agents might be associated with a reduced risk of thrombotic events. [less ▲]

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See detailPrediction of Relapse After Anti-Tumor Necrosis Factor Cessation in Crohn's Disease: Individual Participant Data Meta-analysis of 1317 Patients From 14 Studies.
Pauwels, Renske W. M.; van der Woude, C. Janneke; Nieboer, Daan et al

in Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association (2021)

BACKGROUND & AIMS: Tools for stratification of relapse risk of Crohn's disease (CD) after anti-tumor necrosis factor (TNF) therapy cessation are needed. We aimed to validate a previously developed ... [more ▼]

BACKGROUND & AIMS: Tools for stratification of relapse risk of Crohn's disease (CD) after anti-tumor necrosis factor (TNF) therapy cessation are needed. We aimed to validate a previously developed prediction model from the diSconTinuation in CrOhn's disease patients in stable Remission on combined therapy with Immunosuppressants (STORI) trial, and to develop an updated model. METHODS: Cohort studies were selected that reported on anti-TNF cessation in 30 or more CD patients in remission. Individual participant data were requested for luminal CD patients and anti-TNF treatment duration of 6 months or longer. The discriminative ability (concordance-statistic [C-statistic]) and calibration (agreement between observed and predicted risks) were explored for the STORI model. Next, an updated prognostic model was constructed, with performance assessment by cross-validation. RESULTS: This individual participant data meta-analysis included 1317 patients from 14 studies in 11 countries. Relapses after anti-TNF cessation occurred in 632 of 1317 patients after a median of 13 months. The pooled 1-year relapse rate was 38%. The STORI prediction model showed poor discriminative ability (C-statistic, 0.51). The updated model reached a moderate discriminative ability (C-statistic, 0.59), and included clinical symptoms at cessation (hazard ratio [HR], 2.2; 95% CI, 1.2-4), younger age at diagnosis (HR, 1.5 for A1 (age at diagnosis ≤16 years) vs A2 (age at diagnosis 17 - 40 years); 95% CI, 1.11-1.89), no concomitant immunosuppressants (HR, 1.4; 95% CI, 1.18-172), smoking (HR, 1.4; 95% CI, 1.15-1.67), second line anti-TNF (HR, 1.3; 95% CI, 1.01-1.69), upper gastrointestinal tract involvement (HR, 1.3 for L4 vs non-L4; 95% CI, 0.96-1.79), adalimumab (HR, 1.22 vs infliximab; 95% CI, 0.99-1.50), age at cessation (HR, 1.2 per 10 years younger; 95% CI, 1-1.33), C-reactive protein (HR, 1.04 per doubling; 95% CI, 1.00-1.08), and longer disease duration (HR, 1.07 per 5 years; 95% CI, 0.98-1.17). In subanalysis, the discriminative ability of the model improved by adding fecal calprotectin (C-statistic, 0.63). CONCLUSIONS: This updated prediction model showed a reasonable discriminative ability, exceeding the performance of a previously published model. It might be useful to guide clinical decisions on anti-TNF therapy cessation in CD patients after further validation. [less ▲]

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See detailChallenges and Opportunities in IBD Clinical Trial Design
Dubinsky, M. C.; Icahn School of Medicine at Mount Sinai, New York; Collins, R. et al

in Gastroenterology (2021), 161(2), 400-404

[No abstract available]

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See detailMacrophage-derived exosomes attenuate fibrosis in airway epithelial cells through delivery of antifibrotic miR-142-3p
GUIOT, Julien ULiege; Cambier, Maureen ULiege; Boeckx, Amandine ULiege et al

in Thorax (2020), 75(10), 870-881

Introduction: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease of unknown aetiology and cure. Recent studies have reported a dysregulation of exosomal microRNAs ... [more ▼]

Introduction: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease of unknown aetiology and cure. Recent studies have reported a dysregulation of exosomal microRNAs (miRs) in the IPF context. However, the impact of IPF-related exosomal miRs on the progression of pulmonary fibrosis is unknown. Methods: Two independent cohorts were enrolled at the ambulatory care polyclinic of Liège University. Exosomes from sputum were obtained from 19 patients with IPF and 23 healthy subjects (HSs) (cohort 1), and the ones from plasma derived from 14 patients with IPF and 14 HSs (cohort 2). Exosomal miR expression was performed by quantitative reverse transcription–PCR. The functional role of exosomal miRs was assessed in vitro by transfecting miR mimics in human alveolar epithelial cells and lung fibroblasts. Results: Exosomal miR analysis showed that miR-142-3p was significantly upregulated in sputum and plasma of patients with IPF (8.06-fold, p<0.0001; 1.64 fold, p=0.008, respectively). Correlation analysis revealed a positive association between exosomal miR-142-3p and the percentage of macrophages from sputum of patients with IPF (r=0.576, p=0.012), suggesting macrophage origin of exosomal miR-142-3p upregulation. The overexpression of miR-142-3p in alveolar epithelial cells and lung fibroblasts was able to reduce the expression of transforming growth factor β receptor 1 (TGFβ-R1) and profibrotic genes. Furthermore, exosomes isolated from macrophages present antifibrotic properties due in part to the repression of TGFβ-R1 by miR-142-3p transfer in target cells. Discussion: Our results suggest that macrophage-derived exosomes may fight against pulmonary fibrosis progression via the delivery of antifibrotic miR-142–3 p to alveolar epithelial cells and lung fibroblasts. [less ▲]

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